Redefining Identity of Disease, Tissues and Cells – A Biomaterials Paradigm

Abhay Pandit

Director, CÚRAM- SFI Research Centre for Medical Devices; National University of Ireland; Galway, Ireland

Abstract

Biomaterials are no longer considered innate structures and using functionalisation and

biofabrication strategies to modulate a desired response whether it is a host or implant is

currently an important focus in current research paradigms. Fundamentally, a thorough

understanding of the host response will enable us to design appropriate strategies. The input

from the host response needs to be weighed in depending on the host disease condition. Our

current inputs have been through a thorough understanding of glyco-proteomics based tools

which we are developing in our laboratory. In addition, biomaterials themselves provide

immense therapeutic benefits which needs to be accounted in the design paradigm. Using

functionalisation strategies such as enzymatic and hyperbranched linking systems, we have been

able to link biomolecules to different structural moieties. The programmed assembly of

biomolecules into higher-order self-organized systems is central to innumerable biological

processes and development of the next generation of biofabricated scaffolds. Recent design

efforts have utilized a glycobiology and developmental biology approach toward both

understanding and engineering supramolecular protein and sugar assemblies.

Biography

Professor Abhay Pandit is the Established Professor in Biomaterials and the Director of a Science Foundation Ireland funded Centre for Research in Medical Devices (CÚRAM) at the National University of Ireland, Galway. Professor Pandit’s research integrates material science and biological paradigms in developing solutions for chronic diseases including neural, musculoskeletal and cardiovascular clinical targets with numerous other targets currently under development. His research is funded by Science Foundation Ireland (SFI), EU Framework program, Enterprise Ireland, Health Research Board, the AO Foundation and industry sources, and in excess of €84 million. He has also established a critical mass of biomaterial expertise in Ireland by securing funding for an SFI funded Strategic Research Cluster. He is the author of 22 patents and has licensed three technologies to medical device companies and authored more than 260 manuscripts. Prof Pandit has successfully supervised 26 Ph.D. students, 17 Master’s students and mentored 25 postdoctoral fellows. He is currently leading the team in the supervision of 15 Ph.D. students, 15 Post doctorates and three research associates.

Acellular Biomaterials for Dental Tissue Repair

Adam D. Celiz

UKRI Future Leaders Fellow and Lecturer, Department of Bioengineering; Imperial College

London, UK

Abstract

Dental disease annually affects billions of patients, and while regenerative dentistry aims to heal

dental tissue after injury, existing polymeric restorative materials, or fillings, do not directly

participate in the healing process in a bioinstructive manner. There is a need for restorative

materials that can support native functions of dental pulp stem cells (DPSCs), which are capable

of regenerating dentin. A polymer microarray formed from commercially available monomers to

rapidly identify materials that support DPSC adhesion is used. Based on these findings, thiol-ene

chemistry is employed to achieve rapid light-curing and minimize residual monomer of the lead

materials. Several triacrylate bulk polymers support DPSC adhesion, proliferation, and

differentiation in vitro, and exhibit stiffness and tensile strength similar to existing dental materials.

Conversely, materials composed of trimethacrylates or bisphenol A glycidyl methacrylate

(BisGMA), which is a monomer standard in dental materials, do not support stem cell adhesion

and negatively impact matrix and signaling pathways. Furthermore, thiol-ene polymerized

triacrylates are used as permanent filling materials at the dentin-pulp interface in direct contact

with irreversibly injured pulp tissue. These acellular materials have potential to enable novel

regenerative dental therapies in the clinic by both restoring teeth and providing a supportive niche

for DPSCs.

Biography

Dr. Celiz’s research focusses on the development of

acellular biomaterials to repair or regenerate tissues. Dr.

Celiz gained his PhD in Chemistry in the Melville

Laboratory for Polymer Synthesis at the University of

Cambridge. Dr. Celiz gained postdoctoral training at the

University of Nottingham and the Wyss Institute for

Biologically Inspired Engineering at Harvard University via

a Marie Curie International Outgoing Fellowship (IOF). In

2017, Dr. Celiz was appointed as Lecturer (Assistant

Professor) in Department of Bioengineering at Imperial

College London. Dr. Celiz’s research has been published in

journals including Science, Nature Materials and Advanced

Materials. Dr Celiz has been awarded several early-career awards including the Larry Hench

Young Investigators Prize from the UK Society for Biomaterials and is currently a holder of a

UKRI Future Leader Fellowship.

Bioactive glasses with tuned ion releasing capability to stimulate stem cells for

tissue engineering

Aldo R. Boccaccini

Institute of Biomaterials, University of Erlangen-Nuremberg, 91058 Erlangen, Germany

Abstract

Biochemical reactions occurring at the interface between bioactive glasses (BGs) and the

biological environment, involving the release of BG ionic dissolution products, are relevant for

both hard and soft tissue regeneration. The development and characterization of ion doped BGs

will be discussed with focus on the effect of different biologically active ions released from BGs

on stem cells, mainly umbilical cord and adipose derived stem cells as well as bone marrow-

derived mesenchymal stem cells (BMSCs). BGs incorporating biologically active ions, such as B,

Sr, Cu, Nb, Co, Li, Mn, will be considered. Indirect cell culture methods using endothelial cells

with or without BMSCs in cell culture inserts exposed to ion dissolution products from BG

scaffolds (e.g. Cu doped) will be presented to show that BMSCs secrete an increased concentration

of vascular endothelial growth factor, thus confirming the angiogenic potential of such BGs. The

results are evaluated regarding the stimulating effect of metallic ions on stem cells, also based on

literature results. The variation of ion concentration in medium as function of time and the time

dependent effects on stem cells will be discussed, which is required for the comprehensive

assessment of BG biological performance with implication for clinical applications.

Biography

Aldo R. Boccaccini is Professor of Biomaterials and Head

of the Institute of Biomaterials at University of Erlangen-

Nuremberg, Germany. He is also Visiting Professor at

Imperial College London. His research activities are in the

broad area of glasses, ceramics and composites for

biomedical applications. He has co-authored more than 850

scientific papers. His work has been cited more than 36,000

times (Scopus®). Boccaccini is Fellow of the Institute of

Materials, Minerals and Mining, American Ceramic

Society, Society of Glass Technology and European

Ceramic Society. He is the Editor-in-Chief of the journal

“Materials Letters” and founding Editor of “Biomedical

Glasses”. He has received numerous international awards, including the Materials Science Prize

of German Materials Society and Turner Award of International Commission on Glass. He is also

a member of the World Academy of Ceramics, National Academy of Engineering and Applied

Sciences of Germany and advisor to the Science and Technology Ministry of Argentina.

Boccaccini serves in the Executive Committee of the Federation of European Materials Societies

and in the Council of the European Society for Biomaterials.

Harnessing proteins and supramolecular events to build advanced

biomaterials

Alvaro Mata

Queen Mary University of London, UK

Abstract

Nature has evolved to grow and heal materials and tissues through self-assembling processes capable of

organizing a wide variety of molecular building-blocks at multiple size scales. While advances in fields

such as nanotechnology and biofabrication are enhancing our capacity to emulate some of these biological

structures, it is increasingly evident that recreation of the complexity and functionality of living systems

will require new ways to build with proteins. This talk will present our laboratory’s efforts to harness

supramolecular events found in nature such as multicomponent self-assembly, protein order-disorder

synergies, and diffusion-reaction processes to engineer advanced protein-based materials. The resulting

materials exhibit properties such as hierarchical organization1-3, the capacity to grow and heal2,3, tuneable

mechanical properties1,2, and spatially controlled bioactivity4,5.

References

1. Elsharkawy et al (2018). Nature Communications, 10.1038/s41467-018-04319-0.

2. Wu et al (2020). Nature Communications, 1182, 10.1038/s41467-020-14716-z.

3. Inostroza-Brito et al (2015). Nature Chemistry, 10.1038/nchem.2349.

4. Hedegaard et al (2018). Advanced Functional Materials, 10.1002/adfm.201703716.

5. Hedegaard et al (2020). Science Advances, 10.1126/sciadv.abb3298.

Biography

Alvaro Mata is Professor in Biomedical Engineering and Biomaterials in the School of Pharmacy

and the Department of Chemical and Environmental Engineering at the University of Nottingham.

He holds a Bachelor's Degree from the University of Kansas, a Master's Degree from the

University of Strathclyde, and a Doctor of Engineering Degree from Cleveland State University

working with Prof. Shuvo Roy at the Cleveland Clinic. He conducted his postdoctoral training

with Prof. Samuel Stupp at Northwestern University. His group focuses on developing innovative

ways to build with biomolecules to engineer active, hierarchical, and living materials that can

recreate complex biological environments. Before joining the University of Nottingham, he helped

established and served as Director of the Institute of Bioengineering at Queen Mary University of

London between 2015-2018 and is now the Chair of the Manufacturing Commercial and

Regulatory Committee of the UK Regenerative Medicine Platform (UKRMP2) – Acellular / Smart

Materials – 3D Architecture Hub. His work has led to seven patents or patent applications;

publications in journals including Nature Chemistry, Nature Communications, Science Advances,

and Advanced Functional Materials; and awards such as a Ramon y Cajal Fellowship and an ERC

Staring Grant.

Harnessing the Host Response for In Situ Cardiovascular Tissue Engineering

– the Challenge of Elastogenesis

Anthal I.P.M. Smits

Assistant Professor and Group Leader ImmunoRegeneration Group, Department of Biomedical

Engineering and the Institute for Complex Molecular Systems (ICMS), Eindhoven University of

Technology, Eindhoven, The Netherlands.

Abstract

The use of acellular resorbable synthetic scaffolds for replacing diseased cardiovascular tissues is

an attractive strategy that has shown great promise in recent preclinical studies and ongoing

clinical trials. These scaffolds are designed to instantaneously take over the functionality of the

replaced tissue upon implantation, and maintain functionality while they are gradually resorbed

and replaced by autologous new tissue by infiltrating cells, directly in situ. This process of in situ

tissue engineering is poorly understood to date, leading to unpredictable variability in outcome.

Moreover, one of the biggest unmet challenges is the in situ regeneration of a functional, native-

like elastin network, which is critical for sustaining long-term functionality of cardiovascular

tissues. In this talk, I will present our efforts in the understanding and controlling of the in situ

formation of functional new cardiovascular tissues (i.e. blood vessels and heart valves) by

modulating the host immune response using resorbable supramolecular elastomers. Specifically, I

will elaborate on our recent results on the influence of biomechanical loads on the inflammatory

and regenerative processes to such scaffolds, and how these may dictate tissue formation and

elastin deposition in particular, both in vitro and in vivo.

Biography

Dr.ir. Anthal Smits was appointed Assistant Professor at

Eindhoven University of Technology in 2016, where he

since initiated and leads the ImmunoRegeneration Group as

one of the main research pillars of the Department of

Biomedical Engineering and the Institute for Complex

Molecular Systems (ICMS). His research is aimed at

modulating the immune response using biomaterials in

order to induce functional, homeostatic tissue regeneration.

His group performs interdisciplinary work, dedicated to

gaining a mechanistic understanding of the interactions

between immune cell behavior, biomaterial design, and

biomechanical loads, in conditions of health and disease.

The main target applications are cardiovascular replacements (e.g. heart valves and blood vessels),

yet the research is curiosity-driven, and applicable to a wide variety of clinical applications. Dr.

Smits is a member of the Heart Valve Society and the Tissue Engineering Young Investigator

Council, among others. He is a leading researcher in various international research programs and

public-private partnerships, such as the Materials-Driven Regeneration program (NWO

Gravitation; 25 M€) and the Cardiac Moonshot within the RegMed-XB program (800,000 €).

Tropoelastin promotes elastic tissue regeneration and restoration

Anthony S. Weiss

McCaughey Chair in Biochemistry, Professor of Biochemistry & Molecular Biotechnology,

Charles Perkins Centre School of Life and Environmental Sciences,

University of Sydney, Australia

Abstract

Elastic tissue does not typically regenerate in adults, so there is demand for ways to restore these

tissues following damage. The stages through which tropoelastin self-assembles into elastin and,

in turn, elastic fibers, are hierarchical and the topic of extensive, ongoing research. It is this

capacity for self-assembly that is of interest for a class of materials that promote the formation of

new elastic tissue.

Processes and a hybrid biomaterial, developed in association with Dr. Suzanne Mithieux in my

lab, are intended to deliver tunable levels of histologically detectable patient elastin into full-

thickness wound sites. This approach addresses a persistent unmet need because repairing wounds

lack this elastic substratum. Previously, dogma asserted that elastin synthesis is attenuated in early

childhood, but we found that we can overcome this restriction by adding exogenous tropoelastin,

regardless of the age of the dermal fibroblast donor. We found how to further enhance synthesis

with older cells by using conditioned media. This approach delivers elastin as a layer on the leading

dermal repair template for contact with the deep dermis in order to deliver prefabricated elastic

fibers to the physiologically appropriate site during surgery to repair scar tissue at sites of healing

full thickness wounds.

Biography

Professor Anthony Weiss PhD AM FRSC FTSE FRSN

FRACI FAIMBE FAICD FBSE FTERM is the McCaughey

Chair in Biochemistry at the University of Sydney. His

research focuses on the assembly of human elastic tissue,

damage and its repair. His awards include the Order of

Australia, Clunies Ross National Science and Technology

Award, Eureka Prize for Innovation in Medical Research,

Premier’s Prize for Science & Engineering Leadership in

Innovation, Roslyn Flora Goulston Prize, NIH Fogarty

International Fellow, David Syme Research Medal,

Amersham Pharmacia Biotechnology Medal, NSW

Commercialization Expo Prize, Australian Innovation

Challenge Award, Fondation des Treilles Scholar, Pauling Prize Medal, Barry Preston Award,

ASBTE Research Excellence Award, FAOBMB Entrepreneurship Award and RACI Applied

Research Medal. Professor Weiss founded the biotechnology clinical stage company Elastagen Pty

Ltd which was sold to Allergan in one of the largest transactions ever completed in the Australian

life science sector. He is an inventor with 105 awarded international patents in 17 patent families.

He is on eleven editorial boards comprising leading journals in the field and is global President-

Elect of TERMIS.

‘Mix and match’: local delivery of protein-based biologics

using responsive microgels

April M. Kloxin

Centennial Development Professor of Chemical and Biomolecular Engineering, Chemical and

Biomolecular Engineering and Materials Science and Engineering, University of Delaware,

Newark, DE, 19716, USA

Abstract

Protein-based biologics, particularly antibodies, are of growing interest owing to their specificity

and therapeutic efficacy, especially for many conditions that traditionally have been difficult to

treat (e.g., metastatic cancer, misregulated wound healing). The use of multiple therapeutics,

combination therapies, that target different aspects of disease mechanisms can be particularly

effective; however, such therapies have a significant risk of systemic toxicity owing to the high

total doses that must be used. Responsive hydrogels offer a facile platform for the local, controlled

release of these large, hydrophilic proteins for the design of personalized combination therapies

while minimizing adverse side effects. Specifically, in this talk, I report the development of mixed

populations of hydrogel microparticles, or microgels, for achieving tunable and tailorable release

profiles of antibodies in vitro and in vivo. Microgels of uniform size and relevance for local

injection were created using microfluidic devices. To achieve tunable and on-demand release

profiles, microgels that respond to either internal (i.e., reducing microenvironments) or external

(i.e., light) cues were designed. Modular building blocks, multifunctional polymers with a variety

of chemical handles, were used to create mixed populations of microgels that localize to desired

tissues and release multiple therapeutics across a range of time scales.

Biography

Professor April M. Kloxin, Ph.D., is Centennial

Development Professor of Chemical and Biomolecular

Engineering at the University of Delaware (UD) and a

member of the Breast Cancer Research Program at the

Helen F. Graham Cancer Center and Research Institute. She

obtained her B.S. (Summa Cum Laude) and M.S. in

Chemical Engineering from North Carolina State University

and Ph.D. in Chemical Engineering from the University of

Colorado, Boulder, as a NASA Graduate Student Research

Program Fellow. She trained as a Howard Hughes Medical

Institute postdoctoral research associate at the University of

Colorado before joining the faculty at UD in 2011. Her

group aims to create unique materials with multiscale property control for addressing outstanding

problems in human health. Her research currently focuses on the design of responsive biomaterials

with multiscale properties and development of controlled, dynamic models of disease and

regeneration. Her honors include a NIH Director’s New Innovator Award, ACS PMSE Arthur K.

Doolittle Award, Susan G. Komen Foundation Career Catalyst Research award, NSF CAREER

award, and a Pew Scholars in Biomedical Sciences award.

Success and Challenges in Biofabrication

Brian Derby

Director, Centre for Digital Fabrication; Professor of Materials Science; Department of

Materials; University of Manchester, Oxford Road, Manchester, M13 9PL, UK.

Abstract

Biofabrication as a scientific/engineering term is now 16 years old. In this period it has rapidly

progressed from being seen as a topic for Science Fiction to now a method for the production of

proto- or in vitro model tissues for tissue-on-a-chip applications. Indeed there are several

commercial organizations that have developed and market commercial Bioprinters. However,

despite these not inconsiderable advances, the original target of printed cell-laden implants or

tissue patches have still not been realized.

This talk will present a review of the key advances that have occurred over the recent past and

identify the key challenge of the dimensions of practical printed tissue models. It is well known

that the diffusion limit in 3D culture of cells limits spheroid size to a few hundred m and that

the capillaries in healthy tissue have a diameter of 5 – 10 m and are typically spaced around 50

m. However, current additive manufacturing routes that are in widespread use in biofabriction

have a resolution > 100 m. New approaches to producing high resolution vascular structures

and models for angiogenesis will be reviewed.

Biography

Professor Derby’s research focusses on the use of a range of

printing methods compatible with the delivery of cells for

applications in regenerative medicine and organ-on-a-chip

development. This has been developed by interdisciplinary

university work, international multi-institute collaborations

and collaboration with industry. In 2004 he hosted, in

Manchester, the First International Workshop in

Biofabrication and has been active in the field since then.

Prof. Derby has authored > 300 peer-reviewed journal

publications. His work has been funded through a range of

agencies including EPSRC, BBSRC and MRC from Research Councils UK, the Wellcome Trust,

British Heart Foundation, Innovate UK, the European Commission and the Office of Naval

research (USA)

Nanofilled electrospun fibers inspired by elastin and natural polymers

Nicola Ciarfaglia, Antonietta Pepe, Antonio Laezza, Brigida Bochicchio*

Associate Professor of Organic Chemistry; Department of Science; University of Basilicata, Via

Ateneo Lucano 10, Potenza, Italy

Abstract

Electrospinning is an emerging technique with applications in tissue engineering for the high

surface area to volume ratio and the interconnected pores of nanofibers. Blending of synthetic

polymers as polylactic acid (PLA) and poly--caprolactone (PCL), together with natural proteins

(Gelatin, Elastin) were conceived until now in order to obtain scaffolds with combination of

strength and biocompatibility usually used in soft-tissue regeneration. Furthermore, the use of

nanoreinforcements as bioglass and/or nanocellulose is aimed to overcome the limited mechanical

performances of the scaffolds. In this work, we have successfully electrospun highly hydrophobic

(PDLLA) and hydrophilic polymers (gelatin and a human tropoelastin-inspired sequence) together

with bioglass microparticles and crystalline nanocellulose as nanoreinforcements in the

perspective of future applications in hard-tissue regeneration (bone). Additionally, PDLLA was

herein adoperated for its faster degradation times in comparison to the most used PLA. The

matrices were cross-linked in order to confer stability in water. Afterward, the matrices were

tested concerning wettability, swelling and Young's elastic modulus. They show complete

wettability and a significative decrease of Young's Modulus after swelling (comprised between 27

and 23 MPa). The value is analogous to that found for electrospun scaffolds composed of collagen,

elastin and PCL. Funding: PON R&I 2014-2020 (572 PON_ARS01_01081).

Biography

Professor Bochicchio’s research focusses on biopolymers

and peptides inspired by elastomeric proteins for tissue

engineering. Professor Bochicchio has authored 60

international peer-reviewed journal publications and Invited

Speaker at 24 International Meetings. Professor

Bochicchio’s research has been supported by Italian

Ministry of University and European Community and also

attracts interest from multinational industrial partners. To

date, she has secured ≈€1.8M (Co-I) research funding from

National Operational Program "Research and Innovation"

2014-2020 in health sector. Professor Bochicchio has

successfully supervised to completion 2 PhD student and 20

MSc students all of whom have remained in engineering/science and or academia. She is currently

involved in the supervision of 1 PhD student. Additionally, she is currently mentoring one PhD

research fellow.

Encanpsulation of ICOS-Fc in biocompatible and biodegradable

nanoparticles elicits novel therapeutic activities

C. Luca Gigliotti

Novaicos s.r.l.s., Spin-off of Università del Piemonte Orientale (UPO), 28100 Novara, Italy

Abstract

ICOS is a T cell co-stimulatory molecule binding ICOSL expressed on several cell types, including

osteoclasts, vascular endothelial cells and several tumor cell types. ICOSL triggering by a soluble

recombinant form of ICOS (ICOS-Fc) inhibits osteoclast activity in vitro and development of

osteoporosis in mice in vivo. Moreover, it inhibits migration of tumor cells in vitro and tumor

metastatization in vivo, but it has no effect on the growth of primary tumors. In this work, we show

that loading of ICOS-Fc into either cross-linked cyclodextrin nanosponges (CDNS) or poly(lactic-

co-glycolic acid) (PLGA) nanoparticles (NP), in order to increase stability, sustain release, and

increase tumor-delivery of the drug, elicits a strong antitumor activity ascribable to inhibition of

tumor neoangiogenesis and resetting of the anti-tumor immune response. The substantial in vivo

activity of ICOS-Fc in NP makes these nanoformulations attractive candidates for modulating

ICOS-Fc activity and eliciting novel therapeutic activities.

Biography

The research of Dr. Gigliotti is outlined in different fields

having as a key point the immune system and the role of the

interaction of the costimulatory molecule ICOS and its

ligand ICOSL in vitro and in vivo. His studies also include

the bone system and, in particular, osteoclasts which are

cells of immune origin. The research gave rise to two

patented drugs inhibiting bone resorption and tumor growth,

respectively. He is currently CEO of Novaicos srls, a

biotech company aimed to develop innovative approaches

to correct tissue dysfunctions.

Nanoscale regulation of adhesion and growth factor signaling by material

mechanical and chemical properties

E. Ada Cavalcanti-Adam

Group Leader, Max Planck Institute for Medical Research; Faculty, Institute of Physical

Chemistry, Heidelberg University; Heidelberg, Germany

Abstract

Mechanical and chemical cues present in the extracellular environment regulate cell adhesion-

mediated responses, such as migration, proliferation and differentiation. Designing materials

which combine adhesive ligands and growth factors at the nanoscale is of great interest to address

how local changes in the extracellular environment regulate cell responses through specific

receptor-ligand interactions. I will present the development of surface functionalization strategies

to control integrin clustering and the generation of cellular forces at the interface during adhesion.

The nanoscale presentation of integrin ligands is also combined with growth factors, namely BMP-

2 and BMP-6, to modulate the osteogenic differentiation of cells. In this talk, I will also discuss

the synergistic effect of BMPs and mechanical cues on osteogenic signaling and

mechanotransduction. By varying the stiffness of polyethylene glycol (PEG)- and hyaluronan

(HA)- based hydrogels which are functionalized with integrin ligands and BMPs, it is possible to

elucidate the interdependency of Smad 1/5 and YAP/TAZ signaling.

Biography

Ada Cavalcanti’s research is centered on the

mechanobiology of cell-matrix adhesion. She combines

surface patterning and functionalization approaches to study

the nanoscale regulation of cell adhesion structures and

signaling. She has authored >60 publications in

international peer-reviewed journals. Her research is

supported by the Max Planck Society and by the German

Science Foundation (DFG) and she has been awarded in

2008 with the prize “for women in science” from UNESCO-

L’Orèal.

Active ageing and osteoporosis: the challenge of the GIOTTO project

Chiara Vitale Brovarone

Department of Applied Science and Technology

Politecnico di Torino

Italy

Osteoporosis is a systemic, degenerative disorder, predominantly affecting postmenopausal

women (1 out of 3) but also men at an advanced age (1 out of 5) that increases the fracture risk. A

number of anti-osteoporotic drugs are available and decrease the fracture risk between 50 and 70%

but they also have important side effects and they do not promote fracture healing.

GIOTTO aims to develop a platform of technologies and materials to treat different types of

osteoporotic fractures and to support the prevention of new fractures.

In particular, we will design and validate three different solutions:

1) A 3D graded scaffold allowing fixations with screws to treat periprosthetic fractures

2) A collagen based fibrous scaffold produced via electrospinning to deal with small, not

confined pelvis fractures

3) A radiopaque, bioresorbable, injectable cement to stabilise vertebral fractures

The three devices will share smart nanobiomaterials able to release chemical and biological cues

to stimulate bone regeneration while reducing bone loss.

For further information please visit: http://www.giottoproject.eu/

Full Professor in Materials Science and Technology, Applied Science and Technology

Department, Politecnico di Torino

Prof. Chiara Vitale-Brovarone, Full Professor in Materials

Science and Technology, Politecnico di Torino where she leads

the IRIS group (Improving Regeneration by Intelligent

Scaffolds). Scopus: 160 papers including research articles and

book chapters, H-index 37, 4000 citations.

She has coordinated the EU projects (FP6 – BIORESS, FP7 -

MATCH and H2020 - MOZART) and she has been Team

leader for the FP7 project RESTORATION. At present, she is

coordinating the H2020 project GIOTTO that aims to develop

innovative devices to treat osteoporotic fractures and she is the

PI of the ERC consolidator grant BOOST.

Her research interests are mainly related to the development of innovative biomaterials ranging

from the macro to the nanoscale (3D-scaffolds, micro and nanoparticles, injectable cement and

smart surfaces with osteoproductive, antibacterial and biomolecule release properties).

She is developing novel approaches to target bone and wound healing and osteoporotic fractures

as well as the fabrication of smart bone scaffolds through rapid prototyping approaches including

bioextrusion, ink-jet printing and electrospinning.

Logical Breakdown: Programming Boolean-based Responsiveness into

Hydrogel Biomaterials

Cole A. DeForest

Dan Evans Assistant Professor, Departments of Chemical Engineering and Bioengineering;

Core Member, Institute for Stem Cell & Regenerative Medicine;

University of Washington, Seattle, Washington, USA

Abstract

The successful transport of drug- and cell-based therapeutics to diseased sites represents a major

barrier in the development of clinical therapies. Targeted delivery can be mediated through

degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here,

we report a modular chemical framework for imparting hydrogels with precise degradative

responsiveness by using multiple environmental cues to trigger reactions that operate user-

programmable Boolean logic. By specifying the molecular architecture and connectivity of

orthogonal stimuli-labile moieties within material crosslinkers, we show selective control over gel

dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we

synthesized seventeen distinct stimuli-responsive materials that collectively yielded all possible

YES/OR/AND logical outputs from input combinations involving enzyme, reductant, and light.

Using these hydrogels, we demonstrate the first sequential and environmentally stimulated release

of small molecules, site-specifically modified proteins, and multiple cell lines in well-defined

combinations from a material. We expect these platforms will find utility in several diverse fields

including drug delivery, diagnostics, and regenerative medicine.

Biography

Dr. Cole A. DeForest is the Dan Evans Career Development

Assistant Professor in the Departments of Chemical

Engineering and Bioengineering, and a core faculty member

of the Institute for Stem Cell & Regenerative Medicine at

the University of Washington (UW) where he began in

2014. He received his B.S.E. degree from Princeton

University in 2006, majoring in Chemical Engineering and

minoring in Material Science Engineering and

Bioengineering. He earned his Ph.D. degree under the

guidance of Dr. Kristi Anseth from the University of

Colorado in Chemical and Biological Engineering with an

additional certificate in Molecular Biophysics. His

postdoctoral research was performed with Dr. David Tirrell in the Divisions of Chemistry and

Chemical Engineering at Caltech. He has authored ~45 peer-reviewed articles, including as the

corresponding author for those appearing in Nature Materials, Nature Chemistry, Advanced

Materials, JACS, and Nature Reviews Materials. Dr. DeForest has received numerous research

awards including the Safeway Early Career Award (2018), NSF CAREER Award (2017), AIChE

35-Under-35 Award (2017), and the Presidential Distinguished Teaching Award (2016, UW’s

highest teaching award).

Multifactional cell-assembled biomaterials

Dimitrios I. Zeugolis

Director, Regenerative, Modular & Developmental Engineering Laboratory (REMODEL),

National University of Ireland Galway (NUI Galway), Galway, Ireland

Abstract

Advanced therapy medicinal products put forward the notion that tissue repair and regeneration

can be accomplished best by recruiting the cells’ innate proficiency to create their own tissue-

specific extracellular matrix with a precision and stoichiometric efficiency still unmatched by man-

made devices. This unprecedented clinical success has been attributed to the secreted, intertwined

network of deposited extracellular matrix, which increases cell survival rate by protecting them

and also acts as a biological glue, enabling localised delivery of the cells and their bioactive and

rich in trophic factors secretome. Despite the striking in various clinical indications outcomes, only

a handful of products have been commercialised. This limited technology transfer from bench-top

to clinic has been attributed to the prolonged cell culture time required to develop an extracellular

matrix rich implantable device (up to 196 days), which is associated with cell phenotype loss and

senescence. This talk will advocate the use of macromolecular crowding, alone or in combination

with other in vitro microenvironment modulators (e.g. oxygen tension, growth factor

supplementation), for the accelerated development of multifunctional biomaterials.

Biography

Dimitrios I. Zeugolis is the Director of the Regenerative,

Modular & Developmental Engineering Laboratory

(REMODEL) at National University of Ireland Galway,

Ireland and University of Ioannina, Greece. Dimitrios is

President-elect of Matrix Biology Ireland and Editorial

Committee member-elect of the Tissue Engineering and

Regenerative Medicine International Society. Dimitrios has

authored >100 peer-reviewed articles, >400 peer-reviewed

conference papers and >15 peer-reviewed book chapters. He

is on the editorial board of >10 journals and acts as reviewer

for >130 journals and >30 funding agencies. Dimitrios has

chaired / co-chaired >15 conferences and >50 symposia and

has acted as advisor in >25 conferences. Dimitrios has secured 2 patents and founded 2 companies.

He has conducted research for >40 companies and has been involved in the development and

commercialisation of numerous food and medical device products.

Triggerable Self-immolative Polymer Delivery Systems: From Polyglyoxylates

to Polyglyoxylamides

Elizabeth R. Gillies

Professor, Department of Chemistry and Department of Chemical and Biochemical Engineering;

Director, Centre for Advanced Materials and Biomaterials Research; The University of Western

Ontario, 1151 Richmond St., London, Canada, N6A 5B7

Abstract

Smart, stimuli-responsive polymers are of significant interest for delivery systems that can be

triggered to release drugs by either intrinsic biological or externally applied stimuli that degrade

the polymers. For most stimuli-responsive polymers, multiple stimuli-mediated reactions are

required to completely break down the polymer. Self-immolative polymers are a special class of

stimuli-responsive polymers that can depolymerize end-to-end upon the cleavage of a stimulus-

responsive end-cap from the polymer terminus. This depolymerization mechanism imparts high

sensitivity to stimuli as well as versatility in that a single polymer backbone can be cleaved by

different stimuli simply by changing the end-cap. This presentation will describe our recent work

on the conversion of polyglyoxylates to polyglyoxylamides (PGAMs) via the amidation of

poly(ethyl glyoxylates). Using different primary amines, PGAMs with varying structures were

synthesized, including water-soluble and cationic versions. In addition, PGAMs with lower critical

solution temperatures (LCST) near 37 ºC were discovered. Depolymerization led to disappearance

of LCST behavior and the aggregation state of the polymers influenced their depolymerization

rates. In vitro studies indicated that the chemical structures of the polymers influenced their

toxicity and some PGAMs were well tolerated by cells. Overall, PGAMs are a new class of smart

polymers for new drug delivery applications.

Biography

Professor Gillies’ research interests are in the development

of biodegradable polymers, stimuli-responsive polymers,

and phosphorus-containing polymers as well as their

biomedical applications. Through multidisciplinary

collaborations with academic partners and companies, she

is working on the development of oral and intra-articular

drug delivery systems, anti-bacterial coatings, and scaffolds

for regenerative medicine. Dr. Gillies has published more

than 125 peer-reviewed journal articles and holds 6

patents/patent applications. She has received a number of

awards including a Tier 2 Canada Research Chair in

Biomaterials Synthesis, E. W. R. Steacie Memorial

Fellowship, Early Researcher Award (Ontario), and Fallona Interdisciplinary Science Award

(Western), and is a member of the Royal Society of Canada College of New Scholars, Artists, and

Scientists.

Biomaterials to Eliminate Bacterial Infections

Andrés J. García

Executive Director, Parker H. Petit Institute for Bioengineering and Bioscience

Regents’ Professor, George W. Woodruff School of Mechanical Engineering

Georgia Institute of Technology, Atlanta, GA, U.S.A.

Abstract

Device-associated infections result in substantial morbidity and mortality and contribute

significantly to the high cost of caring for patients. Current therapies to eliminate biofilm formation

in medical devices have shown low levels of success due to the inherent resistance of the biofilm

towards antimicrobial agents, as well as the diverse methods in which bacteria can be introduced

to the site of infection. Lysostaphin is an enzyme that cleaves the pentaglycine cross-links of the

staphylococcal cell wall, leading to cell lysis, making it a potentially useful agent to eradicate

infection in both sites of bacterial growth, as well as established biofilms. We have engineered a

synthetic hydrogel for the encapsulation and delivery of lysostaphin to the site of infection.

Lysostaphin-delivering hydrogels eradicated S. aureus infection and out-performed prophylactic

antibiotic and soluble lysostaphin therapy after 7 days in a murine model of femur fracture.

Infected fractures treated with lysostaphin-delivering hydrogels completely healed by 5 weeks

with equivalent bone formation and mechanical properties to uninfected fractures, whereas

fractures treated without the hydrogel carrier were equivalent to untreated infections. Finally,

lysostaphin-delivering hydrogels were effective against methicillin-resistant S. aureus infections.

Biography

Prof. García’s research program integrates innovative

engineering, materials science, and cell biology concepts

and technologies to create cell-instructive biomaterials for

regenerative medicine and generate new knowledge in

mechanobiology. This cross-disciplinary effort has resulted

in new biomaterial platforms that elicit targeted cellular

responses and tissue repair in various biomedical

applications, innovative technologies to study and exploit

cell adhesive interactions, and new mechanistic insights into

the interplay of mechanics and cell biology. In addition, his

research has generated intellectual property and licensing

agreements with start-up and multi-national companies. He

has received several distinctions, including the Young Investigator Award from the Society for

Biomaterials, the Clemson Award for Basic Science from the Society for Biomaterials, and the

International Award from the European Society for Biomaterials. He is an elected Fellow of

Biomaterials Science and Engineering, Fellow of the American Association for the Advancement

of Science, Fellow of the American Society of Mechanical Engineers, and Fellow of the American

Institute for Medical and Biological Engineering. He served as President for the U.S. Society for

Biomaterials in 2018-2019.

Directing tissue regeneration (and stem cell differentiation) with ions released

from materials.

Gavin Jell

Associate Professor of Nanotechnology & Regenerative Medicine; Division of Surgery and

Interventional Science, University College London

Abstract

Ions released (in a controlled manner) from materials can promote desirable cellular behavior and

tissue regeneration. A range of materials have been designed to release different therapeutic ions

(including Ag, B, Ca, Co, Cu, K, Li, Mg, P and Si), which have (either individually or in

combination with other ions) been reported to promote tissue regeneration including; antimicrobial

activity, angiogenesis, cell survival, desirable ECM production, stem cell recruitment and stem

cell differentiation. The performance and application of these ion releasing materials could,

however, be improved by gaining a greater understanding of the intracellular role of the ions in

directing cell behavior (including stem cell differentiation), by understanding their effect on

different stages on tissue regeneration, and by tailoring the ion release profile for patient-specific

characteristics. Indeed, despite passing the 50th year anniversary since the creation of arguably the

first ion releasing material in medicine, Bioglass® by Prof. L. Hench, there remains a lack of

understanding of how these ions interact with cells, how they regulate gene expression and how

they can be used to direct cellular differentiation.

Biography

Gavin’s research focusses on understanding material-

biological interactions, to create improved biomaterials;

materials that have reduced failure rates and increased

functionality (e.g. promote tissue regeneration or improved

nanoparticle targeting). He is an interdisciplinary scientist

with over 60 publications in bone tissue engineering, soft

and hard tissue implant failure, and nanomedicine. Among

his successes is the invention of Co releasing of bioactive

glasses in 2009 at Imperial College, which is (possibly) the

first bioceramic to target a particular intracellular pathway,

namely the HIF-1α pathway. He’s a Trustee for the British

Society of Nanomedicine and a passionate educator. He has

created a number of successful post-graduate and undergraduate courses and is currently the course

director for MSc in Nanotechnology & Regenerative Medicine (with over 200 graduates), the iBSc

in Surgical Science and a new cross faculty BSc in Medical Innovation and Enterprise. He

currently supervises 9 PhD students and 2 postdoctoral researchers.

Bio-mimetic Tissue Models for Disease Modelling and Testing New Materials

Ghaemmaghami, Amir

Immunology & Immune-bioengineering, Faculty of Medicine & Health Sciences, University of

Nottingham, United Kingdom

Despite emergence of many promising new drug leads and biomaterials there is still a substantial gap

between biological effects observed in in vitro and pre-clinical animal models and the safety and efficacy

of new drugs and materials when tested and used in patients. This has substantial cost and time implications

making introducing efficient and safe new drugs and medical devices and expensive and lengthy endeavour.

These issues are partly due limited physiological relevance of animal models to human and the lack of bio-

mimetic human based tissue models that can be sued for disease modelling and/or testing new drugs and

materials for both safety and efficacy.

In this presentation we discuss our approach for developing biomimetic models of human barrier tissues

with emphasis on the importance of stromal-epithelial cross-talk and the role of immune cells in

investigating inflammatory responses. By simulating key aspects of structural and functional features of

these tissues it would be possible to use in vitro models for disease modelling and testing the efficacy and

safety of new drug leads or chemicals. We will discuss some examples of such applications. Furthermore,

monitoring cellular responses and microenvironmental changes in 3D tissue models is not straightforward

and often involves physical probing or terminating experiments to collect cells or supernatants. Here, we

discuss different strategies for real-time and non-invasive monitoring of cellular responses and changes in

microenvironment in 3D tissue models. This capability will enable the use of these models in repeat-dose

and longer-term experiments providing higher physiological relevance and more in depth understanding of

cellular responses.

Biography

Amir Ghaemmaghami is Professor of Immunology & Immuno-

bioengineering at the Faculty of Medicine and Health Sciences,

University of Nottingham, United Kingdom. He obtained his

MD (1996) before studying for a PhD in Immunology (2002) at

the University of Nottingham. After a period of postdoctoral

training in universities of Leicester and Nottingham, in 2006 he

was appointed as a Lecturer in Immunology in the Institute of

Infection, Immunity and Inflammation at the Faculty of Medicine

and Health Sciences, University of Nottingham followed by his

promotion to Chair in Immunology & Immuno-bioengineering in

2014. Professor Ghaemmaghami’s research is focused on

understanding the interaction between the immune system and

environmental stimuli with an emphasis on the role of antigen

presenting cells in immune regulation. His group’s work in the area of innate immune recognition has led

to many novel findings in the field. More recently his work has focused on developing ‘immune-competent’

tissue models and ‘immune-instructive’ biomaterials for applications in regenerative medicine,

vaccinations and implantable medical devices. Professor Ghaemmaghami is a Follow of the Royal Society

of Biologists and the UK Higher Education Academy and has served on various Editorial/Advisory Boards

and international research funding panels.

Improve Patients’ Lives Using Biomaterials and Tissue Engineered Solutions

for Complex Limb Reconstruction – a Surgeons View of the History and

Current Opportunities

Andrew Hart

Consultant Hand, Plastic & Reconstructive Surgeon, Canniesburn Plastic Surgery Unit,

Glasgow; The Scottish National Brachial Plexus Injury Service.

Professor of Plastic Surgery Research, College of Medical Veterinary & Life Sciences, The

University of Glasgow

Editor-in-Chief, the Journal of Plastic Reconstructive & Aesthetic Surgery

Abstract

Hand, Plastic & Reconstructive Surgery has a long history of using bioengineering knowledge and

engineered solutions to enhance clinical practice, from fracture management and microsurgical

equipment, to the behaviour of cartilage and tendon mechanics. As an interface specialty with a

high prevalence of doctoral research experience, we are optimally placed to aid translational

development and implementation of new technologies.

Glasgow has seen internationally significant developments in transplant immunology and

microsurgery led by its plastic surgeons, amongst others. The need for clinicians, engineers, and

scientists to work within shared research pathways to build understanding and common purpose is

central to the future evolution of limb reconstruction. In this talk, salient aspects of significant

historical interaction between local clinicians and engineers / scientists will be detailed, to shed

light upon the ways forward in the fields of bone and peripheral nerve regeneration using

bioengineered and tissue engineered approaches.

The place for these technologies in the reconstruction of complex oncological, traumatic, and

congenital limb abnormalities will be considered. From enhancing autologous reconstructive

techniques through use of engineered products, to broadening the future horizons of reconstructive

transplantation and intelligent motile prosthetics, the potential for a new, shared, approach to

reconstruction will be elucidated.

Biography

Professor Hart is an internationally trained academic Consultant Hand,

Plastic & Reconstructive Surgeon. He has subspecialty clinical expertise

in major nerve injury, and the microsurgical reconstruction and

reanimation of the hand and upper limb. As Editor of Europe’s leading

Reconstructive Surgery Journal (JPRAS) he has an overview of cutting

edge developments in the specialty, and high level engagement in national

and international societies focused upon developing the clinical

technologies and translational research base for reconstruction (e.g.

BAPRAS, EPSRC, EURAPS, Sunderland Society). In collaboration with

academic groups in Glasgow, London, Manchester and Umeå, he has

focused upon the neurobiology of peripheral nerve injury and regeneration,

and tissue engineering approaches, and guided research direction and

supervision of 14 doctoral theses, with four ongoing. He has recruited

major grant funding including the NC3R’s CrackIt DRGNet contract. A regular invited speaker

to national/international societies and teaching programmes, he also works to build interaction and

understanding between surgeons, bioengineers, and tissue scientists within the EPSRC lifetime

Centre for Doctoral Training in the University of Glasgow’s Centre for the Cellular

Microenvironment.

Nanomedicine within Biomaterials for Healthcare Applications

Helen O McCarthy

Associate Dean of the Graduate School; Professor of Nanomedicine;

School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL

Abstract

This talk will focus on the application of a non-viral peptide to deliver nucleic acid therapies from

two different biomaterials for vaccine and wound healing applications. Nucleic acid vaccination

holds appeal for those patients with a particular disease, particularly as both a prophylactic and

therapeutic effect can occur. However, the bottle-neck in nucleic acid vaccination lies in an

effective delivery technology. Our ‘solution’ to this problem is a two-pronged approach of; i) a

peptide delivery system, termed RALA, that is able to wrap the nucleic acids into nanoparticles,

protect the nucleic acid from degradation, enter cells, disrupt endosomes and deliver the cargo to

the cytoplasm (mRNA) or nucleus (DNA) ii) a microneedle patch (MN) that will house the

nanoparticles within the polymer matrix, painlessly breach the skin’s stratum corneum barrier and

dissolve upon contact with skin interstitial fluid thus releasing the nanoparticles into the skin to

the antigen presenting cells. Using our novel technology platform we have created both DNA and

RNA vaccine for cervical cancer in a dissolvable microneedle patch and demonstrated both

prophylactic and therapeutic responses in vivo. We have also developed an electrospun

nanofibrous wound healing patch loaded with RALA nanoparticles with siRNA designed give

temporal downregulation of the FK506-binding protein-like (FKBPL) gene in order to promote

angiogenesis. The nanofibrous patch was designed to accommodate the nanomedicine specifically

for wound healing and in vivo studies demonstrated a functional prototype.

Biography

Professor McCarthy’s research team focuses on the development of

non-viral delivery systems for nanomedicine applications. These

biomimetic systems are designed to overcome the extra and

intracellular barriers, so that the macromolecular payload can be

delivered at the destination site in order to exert the optimal

therapeutic effect. We have designed and patented a peptide delivery

system, termed RALA that is able condense large and small anionic

entities into nanoparticles, protect the cargo from degradation, cross

cell membranes, escape endosomes and deliver the cargo to the

cytoplasm and nucleus. Current research projects involve gene

therapy for metastatic deposits; miRNA therapeutics for oncology and

wound healing applications; mRNA and DNA vaccination strategies;

repurposing of bisphosphonates and regeneration of bone by increasing the bioavailability of

ceramics. The wide-spread utility of RALA delivery system has led to a spin-out company pHion

Therapeutics www.phiontx.co.uk. Phion have commenced two lead therapeutic pre-clinical

development programs supported by Innovate UK funding (i) a RALA/mRNA therapeutic vaccine

for HPV; and (ii) a tumour targeted chemotherapeutic for pancreatic cancer.

https://scholar.google.co.uk/citations?user=-4C6BasAAAAJ&hl=en

Clinical Translation in Biofabrication

James J. Yoo

Professor, Wake Forest Institute for Regenerative Medicine; Wake Forest School of Medicine;

Winston-Salem, North Carolina, USA

Abstract

The US Department of Health and Human Services has recognized regenerative medicine as an

innovative scientific field that would become the standard of care for replacing tissue/organ

systems in the human body. As such, recent advances in this field have offered new therapeutic

opportunities that facilitate the restoration and maintenance of normal tissue function. Various

engineering strategies have been developed and applied to build functional tissues and organs for

clinical applications. While techniques developed for tissue engineering and regenerative medicine

applications have had initial successes in building a number of tissues clinically, challenges still

exist in developing complex tissue systems. In recent years, 3D bioprinting has emerged as an

innovative tool that enables the rapid construction of complex 3D tissue structures with precision

and reproducibility. In this session novel and versatile approaches to building tissue structures

using 3D printing technology will be discussed. Clinical perspectives unique to 3D printed

structures will also be discussed.

Biography

Dr. Yoo is Professor and Associate Director of the Wake

Forest Institute for Regenerative Medicine (WFIRM), with

a cross-appointment to the Departments of Urology,

Physiology and Pharmacology, and the Virginia Tech-Wake

Forest School of Biomedical Engineering and Sciences. Dr.

Yoo's research efforts have been directed toward the clinical

translation of tissue engineering technologies and cell-based

therapies. Dr. Yoo's background in cell biology and

medicine has facilitated the transfer of several cell-based

technologies from the bench-top to the bedside. A few

notable examples of successful clinical translation include

the bladder, urethra, vagina, and muscle cell therapy for incontinence. Dr. Yoo has been a lead

scientist in the bioprinting program at WFIRM and has been instrumental in developing skin

bioprinting and integrated tissue and organ printing (ITOP) systems for preclinical and clinical

applications.

What Value Can Bio-based Materials Bring to the Life Science and Clinical

Markets?

Johana Kuncová-Kallio

Director, UPM Biomedicals, UPM, Alvar Aallon katu 1, PO Box 380 | 00101 Helsinki,

FINLAND

Abstract

In the search for alternatives to synthetic or animal-based products for research and clinical

applications, attention has turned to the potential offered by bio-based materials. Nanofibrillar

cellulose in particular, has specific physical characteristics which make it an ideal candidate for

applications such as 3D cell culture, 3D printing and wound care and other extractives such as

lignin have shown promise in electrospinning. An overview of bio-based materials, specifically

those derived from wood, will be presented and their potential investigated.

Biography

Johana works in the fields of cell technology and diagnostics

since 2000. The topics ranged from single cell handling and

analysis, biomimetic environments for cell cultivation and

stem cell differentiation, to point-of-care diagnostics,

biosensors, nanoparticle characterization and surface

modifications.

She acted as an evaluator for Dutch Technology Foundation

and for the European Commission. She has been involved

in the Finnish national initiatives of Research Tissue Bank

Finland, Infrastructure for Personalized Treatments, as well

as in the building of BioMediTech institute combining the

medical doctors with engineers. She has established several

courses and still gives lectures in the fields where biology meets technology. Besides that, she acts

as a mentor and advances the skills of others in the fields of presentation skills, career development

and nanotechnology start-ups.

During her career, she was involved as a business advisor, investor and/or board member in several

spin-offs from universities as well as from companies. Before joining UPM, she was a CEO of a

scientific instrumentation manufacturer. At UPM, she is responsible for the development of

business in Life Science and Clinical sectors.

Abstract 1

New approaches for immunological medical product testing – Analysis of macrophage

phenotypes in direct contact with the material surface

Susanne Kurz, Juliane Spohn

Fraunhofer Institute for Ceramic Technologies and Systems IKTS, Dresden

Macrophages play a central role in tissue healing and regeneration at the implant site. The transition

from an inflammatory (M1) to an anti-inflammatory (M2) macrophage phenotype is required to ensure

a normal wound healing process, thus promoting the functional integration and the long-term stability

of the implant. The implant itself, with its physical and chemical characteristics, may influence this

transition in a positive or negative way. Safety and functionality has to be demonstrated for each

implantable medical product. Biological safety testing, as for example testing for cytotoxicity according

to ISO 10993 thereby concentrates on two scenarios: 1) Studies on extractable and leachable substances,

and 2) studies focusing on the direct cell-material-contact. With regard to macrophage activation both

test scenarios are of importance as macrophage polarization might be influenced by compounds released

by the implant itself as well as by physical- and chemical features of the implant surface. We concentrate

on developing test scenarios and new possible analysis strategies. Especially in the field of direct

implant-cell-interaction we work on new analytical methods and tools which allow for fast and

automatable determination of macrophage phenotype. We here introduce our approaches that may help

to develop standardizable test scenarios for bio- and immunological testing of medical products.

Abstract 2

Biomaterial Testing 2.0 – New in vitro test system for the quantification of cell response in direct

contact to the material

Constantin Ißleib, Susanne Kurz, Juliane Spohn

Fraunhofer Institute for Ceramic Technologies and Systems IKTS, Dresden

For biocompatibility tests scientists rely on standardized, biocompatible plastic cell culture plates with

known geometry and size of culture area. However, testing of solid biomaterial and implant material in

this standardized plates is often challenging. First the biomaterial has to fit in the standardized well size.

One major disadvantage of placing the biomaterial into a well is that plastic culture area surrounding

the biomaterial is left and needs to be taken into account when evaluating the collected data. Additionally

accurate prediction of cellular behavior around the edges and the bottom side of the biomaterial is

complicated. This may also be a reason why quantitative analysis of biological response of cells in the

direct contact to medical products are underrepresented in the biological testing guidelines like the ISO

10993. In this work, we introduce our lab solution for creating standardized wells on a wide range of

solid biomaterials, which are fully comparable to cell culture well geometry. The system is adaptable to

different material sizes and roughness as well as standard plastic and glass slides. Applications like

quantification of direct cell contact assays, cell secretion assays or protein adsorption assays are easy to

handle in our device thereby allowing replicable and multiple assaying on the same biomaterial. Here

we describe the use of our device for the quantitative testing of macrophage polarization in direct contact

limited to the biomaterial surface of interest.

Abstract 3

Specific cell model for immunological medical product testing – Cell line based macrophage

model (M1/M2 switch)

Samuel Scholl, Susanne Kurz, Constantin Ißleib, Juliane Spohn

Fraunhofer Institute for Ceramic Technologies and Systems IKTS, Dresden

One of the main reason for aseptic loosening of implants, as the most important cause for implant failure,

is the unsuccessful resolution of acute inflammation after implantation. Macrophages at the implant site

drive this inflammation due to their activated inflammatory phenotype. Macrophages are known to

remove pathogens causing an inflammatory environment and thereby recruiting other immune cells to

the area of infection. The surgery as the initial event of implantation is said to cause a sterile

inflammation mainly caused by damaged cells and tissue and to a less extent by pathogens. The cell

damage provides a macrophage activating environment enriched on damage associated molecular

pattern (DAMPs) leading to the activation and polarization of macrophages to the inflammatory (M1)

phenotype. The transition of the inflammatory M1 phenotype to an anti-inflammatory phenotype (M2)

represents the successful resolution of the inflammation and the initiation of the normal wound healing

process. Implant materials should therefore ideally promote this transition of M1 to M2 macrophages or

at least avoid influencing it (functionality and/or safety of the implant material). Why not to test this

macrophage influencing properties of implantable medical products before they get in contact with the

test animal or human body at the in vitro cellular level? For such a test the cell model should resemble

the in vivo like conditions at the implant site as good as possible. Thereby the test should be fast,

transferable, standardized and easy to analyze. Here we describe and show first results of our test

scenario, which is based on a compilation of scientific approaches. It is appropriate for the testing of

macrophage modulating properties of implantable medical products in the test scenario with direct cell-

material-contact as well as in the indirect material test scenario (studies on extractable and leachable

substances).

Biosketch: Juliane Spohn

Dr. rer. nat. Juliane Spohn earned her doctorate in 2013 at the University of Rostock in the working

group Clinical Immunology. During her postdoc phase she worked in numerous projects with

industrial partners and research institutions at OUK (Orthopediatric Clinic and Polyclinic) in Rostock

till 2015 and gained knowledge in the field of immunobiological testing and development of

biomaterials and appropriate test methods. In addition to the subject-specific suitability in the field of

implantology and immunology, she is experienced in the planning, implementation and evaluation /

documentation of in vitro and in vivo examinations. Juliane Spohn has been working at the Fraunhofer

IKTS since 2016 and established her own Research group “Biological Materials Analysis” at the

external location (Fraunhofer Institute for Cell Therapy and Immunology, IZI) in Leipzig.

Biofabrication – Chances, Challenges and Current Limitations

Jürgen Groll

Full Professor, Chair and head of the Department of Functional Materials in Medicine and

Dentistry, University of Würzburg, and Head of the KeyLab Polymers for Medicine, Bavarian

Polymer Institute, Würzburg, Germany

Abstract

Biofabrication is a young field of research that aims at the automated generation of hierarchical

tissue-like structures from cells and materials through automated procedures in Bioprinting or

Bioassembly [1]. This approach has the potential to overcome a number of classical challenges in

relating to organization, personalized shape and mechanical integrity of generated constructs.

Despite some remarkable early successes, the lack of variety in materials that can be formulated

together with cells for Bioprinting, so called Bioinks [2], has for long been one major drawback

for the field [3]. However, recent years have seen tremendous progress, and current changes rather

lie in the transformation of the now existing fabrication power to structures with biological

function. This contribution will give an introduction to the field, critically review the current status,

including examples of our recent work, and also concern some of the current challenges.

References

[1] J. Groll, et al.: Biofabrication: Reappraising the definition of an evolving field. Biofabrication,

8, 013001 (2016)

[2] J. Groll, et al.: A Definition of Bioinks and their Distinction from Biomaterial Inks.

Biofabrication, 11, 013001 (2019)

[3] T. Jüngst, et al.: Strategies and Molecular Design Criteria for 3D Printable Hydrogels.

Chemical Reviews, 116 (3), 1496 (2016)

Biography

Jürgen Groll’s research interest comprises applied polymer

chemistry, nanobiotechnology, immuno-modulatory and

regenerative materials and biofabrication. He coordinated the

large-scale integrated European project HydroZONES (contract

no 309962; 2012 – 2017) and was awarded an ERC consolidator

grant (Design2Heal, contract no° 617989). Currently he acts as

founding spokesman of the Collaborative research Center TRR

225 “From the fundamentals of biofabrication towards func-

tional tissue models” (http://trr225biofab.de/), an integrated

funding scheme of the German Research Foundation that is

running between the Universities of Würzburg, Bayreuth and

Erlangen-Nürnberg, comprising 18 research projects and 36

PhD students that are supervised by 36 PIs. He has published over 170 papers in peer-reviewed

scientific journals. For his work, he received a number of awards, such as the Henkel Innovation

Award (2007), the Bayer Early Excellence in Science Award (2009), the Reimund-Stadler Award

of the German Chemical Society (2010) and the Unilever Prize of the Polymer Networks Group

(2014). He currently serves as editorial board member of the journal biofabrication and as board

member of the international society for biofabrication.

Immune response deciphering interactions on the biomaterial-body interface by the

advanced immunoprofiling: impacts on implants and medical devices

Kaia Palm, Protobios, Estonia

Mariliis Jaago1, 2, Arno Pihlak1, Helle Sadam1,2, Valentina Bozok1, Miljana Bacevic3, France

Lambert,3 Nihal Engin Vrana4,5 and Kaia Palm1,2*

1 Protobios Llc, Mäealuse 4, 12618 Tallinn, Estonia; 2 Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15,

12618 Tallinn, Estonia; 3 Department of Periodontology and Oral Surgery at Liège University, Domaine Universitaire du Sart

Tilman, Bat B 35, B-4000 Liège, France

4SPARTHA Medical, 14B Rue de la Canardiere, 67100, Strasbourg, France; 5INSERM UMR 1121, 11 Rue Humann, 67000, Strasbourg, France.

Abstract

The demand for biomaterials has increased rapidly due to societal ageing and accompanying surge in the

demand of anti-ageing agents. However, introducing biomaterials to the body induces early immunogenic

effects and further down chronic immune response due to the degradation products released by devices

(tissue engineered scaffolds, orthopedic implants, biomedical devices) that combined determine the

outcome of the integration and the biological performance of the implant. Currently, clinical uptake of

biomaterials is poor.

In recent years, quantitative immunomics has developed rapidly, offering systems level immune response

analysis and personalized medicine at high-throughput. Mimotope Variation Analysis (MVA) is a powerful

tool to characterize the immune response profiles in a blood sample against millions of synthetic peptide

antigens simultaneously. Here, this approach has been used to delineate immunoprofiles of biomaterials

and to predict the response to biomaterial (BM) accommodation by the body.

Using MVA immunoprofiling technology, several specific amino acid patterns were predicted to be

associated with certain antibody response profiles to BMs. The immune response to any foreign material

was found to be highly individual. The individual epitopes displayed by different peptide sequences varied

in abundance. These were quite frequently detected in some individuals while not detected at all in others.

The observed high variance of specific epitope targeting patterns across studied cohort (one BM might elicit

a very different response in one individual vs the other) and across BMs (for one person, a certain BM

might be more compatible with the body than the other) highlighted the necessity for a multiplexed, robust

and fast assay system to be used in the BM selection process for biomedical development and clinical care.

In sum, MVA data allowed to define antibody response signatures, whose presence might be enhanced due

to their pre-existing nature by implanted BM and thus misdirect immune responses against self, against

microbiota or environmental derived antigens.

Acknowledgement (optional): The research was funded by the institutional research grant of Protobios (nr

5.1-4/1373) and by personal research grant of KP (PRG578) from the Estonian Research Council. Protobios

team was supported by EU H2020 RIA research funding (PanBioRa, EU760921).

Biography

Dr. Kaia Palm (Ph.D), CEO, (f): She graduated from the Faculty

of Chemistry, University of Tartu, Estonia, defended her PhD in

1998 in Karolinska Institute, Sweden, with specialization on

molecular neurobiology. During her post-doc studies, in years

1998-2001, Kaia participated in the original clinical trials of

autologous stem cell-therapy for the treatment of the Parkinson’s

disease at Cedars-Sinai Medical Hospital, LA, USA. She has

more than 15 years of experience in academia as associate

professor at Tallinn University of Technology, Estonia, and more

than 14 years of experience in the biotech business. Dr. Palm has

published >30 peer-reviewed publications and is the co- inventor

of 15 patents. Acting as the CEO of Protobios, she has led the MVA technology development activities.

Under her chair, Protobios has become one of the most innovative biotech companies in the region and

holds a globally competitive position in biomarker discovery and as service provider in the field of

immunomics.

High content imaging of cells and 3D in vitro tissues

Katja Schenke-Layland1,2,3

Director of 1The Natural and Medical Sciences Institute (NMI) at the University of Tübingen,

Reutlingen, Germany; Professor in the 2Department of Women’s Health, Research Institute for

Women’s Health, Eberhard Karls University Tübingen, Tübingen, Germany and the 3Department

of Medicine/Cardiology, Cardiovascular Research Laboratories (CVRL), University of

California (UCLA), Los Angeles, CA, USA

As the field of regenerative and personalized medicine matures, the need for novel enabling

technologies to characterize cells and engineered constructs (i.e. cells/tissue combined with

biomaterials and three-dimensional (3D) scaffolds) as well as their individual components in a

more insightful, quantitative and preferably non-invasive manner becomes imperative. Raman

microspectroscopy and imaging as well as fluorescence lifetime imaging (FLIM) are emerging

techniques that allow the assessment of molecular interactions and the biochemical structure of a

sample in a non-invasive, marker-independent manner. Specifically for tissue engineering

applications, it has been proven to allow determining biochemical information on cells, tissues

and/or material-cell tissue constructs without the need for labels. The presentation aims to show

the applicability of Raman technologies and FLIM for regenerative and personalized medicine

applications, and to discuss the added value of the generated data for tissue engineering construct

design optimization and preclinical as well as clinical applications.

Biography

Professor Schenke-Layland’s main research interests

revolve around the role of the extracellular matrix in tissue

engineering and regenerative medicine, the translation of

human developmental biological data into therapeutic

strategies, and the non-invasive monitoring of biological

processes. Prof. Katja Schenke-Layland currently holds a

dual appointment as a full professor (W3) at the University

Women’s Hospital and as Director of the Natural and

Medical Sciences Institute (NMI) Reutlingen in Germany.

She is also affiliated with the Department of

Medicine/Cardiology at the University of California in Los Angeles, USA. She is an executive

editor for Advanced Drug Delivery Reviews, which is one of the top journals in the field of

advanced gene and drug delivery, and co-editor-in-chief of Tissue Engineering, Part B. To date,

she has secured more than in 11.8 Mio € individual research funding as PI, has published 129

peer-reviewed manuscripts with more than 4600 citationsScopus and has an h-Index of 39Scopus.

Designing Bioinks for 3D Bioprinting

Dr Khoon Lim, PhD, MRSNZ

Senior Research Fellow, Department of Orthopedic Surgery and Musculoskeletal Medicine

Team Leader, Christchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group

University of Otago, Christchurch, New Zealand

Abstract

3D Bioprinting requires specialized bioinks that is able to be printed but also protect the cells

during the printing process. These bioinks are often biomaterials with specific rheological

properties that allows spatial extrusion in a layer-by-layer manner, but also being cyto-compatible

to support cellular viability and function. In addition, photo-initiated radical polymerisation which

is combining light and photo-initiators to generate radicals for crosslinking photo-polymerisable

macromers has been employed in 3D biofabrication of cell-laden hydrogel constructs. The major

advantage of using this technology is the spatio-temporal control over the crosslinking process, as

well as being able to fabricate constructs with tailorable physico-mechanical properties. This

lecture will cover the different design criteria required for bioinks, as well as the variety of

materials being employed to manufacture these bioinks. Specific focus will be placed on the

various chemistries used to synthesize polymers, photo-initiating systems to crosslink the

polymers, as well as strategies to maintain bioprinted constructs’ stability. Moreover, these

chemistries and strategies will also be compared between different biofabrication platforms,

including extrusion bioprinting, lithography-based technologies and bioassembly. The

combination of various materials, crosslinking chemistries and photo-initiating systems is crucial

in tailoring the biofabrication window to fit multiple applications.

Biography

Dr Khoon Lim is currently a Senior Research Fellow and

team leader at the University Of Otago Christchurch New

Zealand. His research focuses on developing photo-

polymerizable hydrogel bioinks for 3D bioprinting of

functional tissues and also delivery of bioactive

molecules to promote tissue regeneration. He has been

awarded a total of > $3 Million research grant funding

($2 Million as PI), including the prestigious Emerging

Researcher First Grant and Sir Charles Hercus Health

Fellowship, both from the Health Research Council of

New Zealand, and also a MARSDEN Fast Start Grant

from the Royal Society of New Zealand. His research has

also generated one full utility patent filed 7 different countries, where he’s the lead inventor. He

currently supervises 10 PhD students, 2 Masters students, and mentors 3 postdoctoral fellows. Dr.

Lim is also Associate Investigator on the Centre of Research Excellence in Medical Technologies

(MedTech CoRE), Affiliate Investigator on the Maurice Wilkins Centre (MWC) for Molecular

Diversity, and Executive Committee member of the Australasian Society of Biomaterials and

Tissue Engineering (ASBTE).

Creating regenerative environments with materials

Liam M Grover

Director, Healthcare Technologies Institute; Full Professor of Biomaterials Science

University of Birmingham. Edgbaston, UK, @DWLiam

Abstract

The long-term outcome following wounding depends strongly on the environment that is created

within the damaged tissue. Acute inflammation results in the upregulation of cytokines such as

TGF-1, which cause the differentiation of cells within the wound into myofibroblasts, cells which

contract the wound bed and deposit collagen more rapidly than the fibroblasts that are normally

present in a tissue. Although this rapid production of collagen and contraction of the wound results

in closure, it also results in scarring, which can cause psychosocial impacts, as well as limiting

movement and if on the surface of the eye, blindness. We have developed a range of technologies

that aim to modulate the wound environment and thereby limit or even eliminate scarring on the

surface of the skin and in the eye. This talk will describe the development of these technologies

that have been designed to limit the scarring process, by sequestering pro-fibrotic growth factors

or reducing their activity in the site of a wound. It will describe how we have taken these

technologies through the translational pathway, from preclinical testing through to manufacture

using GMP processes. It will also highlight some of the hurdles that we have had to overcome in

taking our novel technologies through to the clinic.

Biography

Liam M Grover is a Professor of Biomaterials Science at the

University of Birmingham. His research focusses on

investigating the interactions between materials and

biological systems, a greater understanding of which has

enabled him to develop a host of novel materials that have

been used for skeletal reconstruction and the treatment of

scarring. He has published more than 180 peer reviewed

publications and filed more than 10 patents. He has raised

in excess of £30m of research funding, and is the founder-

director of the Healthcare Technologies Institute, which is

based in the Institute of Translational Medicine at the

University of Birmingham. The institute seeks to take novel

interventions to the point of clinical trial, supporting the full translational process. He has taken

three new medical interventions to the point of clinical trial. He was the youngest full Professor

ever appointed to the University of Birmingham at the age of 32.

Advanced Biofabrication Methods for Cellular Grafts

Marcy Zenobi-Wong

Director, Institute for Biomechanics; Associate Professor of Tissue Engineering +

Biofabrication;ETH Zürich, Zürich, Switzerland

Abstract

Of the many evolving biofabrication approaches, microextrusion bioprinting has been the most

commonly applied in tissue engineering. In order to recreate complex geometries and large scale,

the typical bioink used in extrusion bioprinting has required the use of viscosity enhancers and/or

support materials to be effective. We have recently explored the class of bioinks called ‘jammed’,

granular or microgel materials for extrusion bioprinting. In our case, we work with microgels with

high aspect ratio and ability to entangle with each other. These entangled bioprinting materials are

less subject to flow instabilities, have natural macroporosity and orientation and can be used in a

modular, multimaterial and multicellular approach. In this lecture, entangled microgel bioinks are

explored in the context of cartilage engineering.

Biography

Dr Marcy Zenobi-Wong is an Associate Professor of Tissue

Engineering and Biofabrication at ETH Zürich,

Switzerland. She obtained her PhD from Stanford

University and then did a post-doctoral fellowship in the

Orthopaedic Research Laboratories, University of

Michigan. In 2012, she moved to the Department of Health

Sciences & Technology at ETH Zürich. The Zenobi-Wong

research group is focused on the development of advanced

biomaterials for tissue regeneration using biofabrication

technologies including bioprinting, two-photon

polymerization, casting and electrospinning. Dr Zenobi-

Wong is the author of over 95 peer-reviewed publications and co-inventor on four licensed patents.

She is currently President of the Swiss Society for Biomaterials and Regenerative Medicine and

General Secretary for the International Society of Biofabrication (ISBF). She serves on the

editorial board for Biofabrication and Advanced Healthcare Materials.

Nanoscale control of mesenchymal stem cells for identification of bioactive

metabolites.

Matthew J Dalby

Co-Director, Centre for the Cellular Microenvironment; Full Professor of Biomedical

Engineering; University of Glasgow, UK

Abstract

Metabolites, or biological small molecules, are usually considered in identification of biomarkers.

However, they can be used to drive cellular processes, such as stem cell differentiation. Use of

complex media recipes to control stem cell differentiation add artefact to metabolomics

experiments and so bioengineering approaches are attractive as they can drive different stem cell

fates without changing what the cells are ‘fed’. We have developed metabolomics pipelines to

identify bioactive metabolites that control mesenchymal stem cell (MSC) self-renewal and

differentiation.

We started this research avenue using peptide hydrogels with defined stiffnesses that could control

MSC chondrogenesis and osteogenesis, identifying GP18:0 and cholesterol sulphate as bioactive

metabolites1. Next, using our nanovibrational bioreactor, the Nanokick2, along with synthetic

chemistry modification of hit metabolites, we focused on refining our putative osteospecifc

metabolite candidates to tune potency and specificity identifying fludrocortisone acetate. Finally,

we have used nanotopography to control MSC self-renewal3 to identify respiration-link

metabolites that drive the immunomodulatory phenotype of MSCs4; this is critical if we wish to

grow large numbers of high quality MSCs for use as immunosuppressive therapies in transplant

procedures.

Alakpa Chem 2016, 2) Tsimbouri Nature BME 2018, 3) McMurray Nature Mat 2011, 4) Ross

BioRxiv 2019.

Biography

After a PhD at Queen Mary University of London on

osteoblast response to bioactive composites. I moved to

Glasgow to study cell-nanoscale interactions. In 2003 I

became an independent researcher securing a BBSRC

David Phillips Fellowship to explore mesenchymal stem

cell response to nanotopography. Appointed to a lectureship

in 2008 and a Readership in 2010, I became Professor of

Cell Engineering at the University of Glasgow in 2014. I

hold grants from EPSRC, MRC, BBSRC, Leverhulme Trust

and Sir Bobby Charlton Foundation. I am director of the

EPSRC-SFI lifETIME centre for doctoral training.

My research has focussed on developing insight into MSC

differentiation and self-renewal using materials and mechanotransductive cues, making

contributions in journals such as Nature Materials, Nature Biomedical Engineering, Advanced

Materials, Chem, Science Advances etc (>180 papers). More recently I have become interested in

using materials to find activity metabolites that can be used to control MSC phenotype. As well as

basic science, I am interested in translational science and have been involved in veterinary bone

regeneration trials and am working now towards a human bone regeneration trail.

In 2016 I was elected a Fellow of the Royal Society of Edinburgh and have won a number of

awards – most recently the Biochemical Society Industrial-Academic Collaboration Award.

BIOMATERIAL RISK ASSESSMENT AND PERSONALISED

BIOMATERIAL TESTING: FROM NANOSCALE TO MACROSCALE

Nihal Engin Vrana

CEO, SPARTHA Medical, 67100, Strasbourg France; Affiliated Researcher, INSERM UMR

1121 University of Strasbourg, 67000, Strasbourg, France

Abstract

The increasing number of implantable biomedical devices and novel biomaterials creates a double pressure

on the current framework on the biomaterial related risk management. The significant variation of the shape,

size and mechanical properties of the organs between the patients necessitates the development of

personalized solutions which can diminish the level of reaction by the host. However, beyond the

anatomical match, the patient’s immunological profile and the specific reactions to a given material must

also be considered for better clinical outcomes. This is particularly relevant for new biomaterials where

unforeseeable side effects due to the unintentional similarities with antigens or unknown biological effects

are possible (such as synthetic polypeptides). The determination of patient specific components of the

adverse immune reactions enables the development of safer personalized solutions. H2020 PANBioRA

project aims to provide the necessary tools for such assessments for decreasing the complications related to

the available implantable devices and facilitating the uptake of new biomaterials for clinical use. The

multiscale approach in the project assesses biomaterials at antibody level, cell level, miniaturized organ and

finally at macro level. This introductory talk will focus on the proposed risk management tools by

PANBioRA system and the introduction of the current version and its components.

ACKNOWLEDGEMENTS: This project has received funding from Horizon 2020 research and

innovation programme under grant agreement No 760921 (PANBioRA).

Biography

Dr. Nihal Engin VRANA is CEO of SPARTHA Medical and an

affiliated researcher in INSERM UMR 1121. He obtained his

PhD in 2009 at Dublin City University as a Marie Curie ESR

fellow. His major research interests are implants, antimicrobial

coatings, tissue engineering, cell encapsulation,

immunomodulation, real-time monitoring of implants,

biomaterial assessment and cell biomaterials interactions. He has

been the scientific coordinator of 2 European Projects

(EuroTransBio Bimot and FP7 IMMODGEL) and he currently

coordinates H2020 PANBioRA project (11 countries, 17 partners,

www.panbiora.eu). He has published 73 articles in peer-reviewed

academic journals (over 2200 citations, h index: 26), 8 book chapters and holds 5 European patents. He

edited two books for Taylor and Francis on Cell Material Interactions (2015) and Immune response to

Biomaterials (2018). His awards include ESB Translational Research award (2011), BPI i-Lab (2019) and

Fond’Action Alsace Future Talents Award (2019) for SPARTHA Medical.

Effect of bioactive glass cotton wool like fibre conditioned medium on bone

marrow derived stem cells

Olga Tsigkou

Lecturer in Biomaterials; Biomaterials Subject Lead; Department of Materials, University of

Manchester, Oxford Road, Manchester, UK

Abstract

Biomaterials science focuses on engineering smart materials that can direct cellular behaviour. In

vivo bone tissue resident adult stem cells are encompassed by a 3D microenvironment that presents

a repertoire of signals, such as matrix rigidity, soluble factors, cell-cell interactions and

extracellular matrix ligands. Ultimately, bone stem cells or bone progenitors respond to these

components by initiating signaling pathways, which control and direct cell function and

differentiation into osteogenic lineage. Bioactive glasses have shown the ability to form

hydroxyapatite through exchange of silicon and calcium ions with interstitial fluids. Silica and

calcium have been reported to be highly beneficial for bone and cartilage health and their dietary

intake has been implicated with increased bone mineral density. In this talk I will report the

development of a bioactive glass electrospun cotton wool like fibres and the effect of their

conditioned medium on bone marrow derived mesenchymal stem cells. I will demonstrate that the

bioactive glass conditioned medium enhance osteogenic differentiation and ECM deposition and

mineralization in vitro 3 times faster than conventional osteogenic supplements. Additionally,

activation of specific intracellular pathways activated and the effect of the 70S30C bioactive glass

conditioned media on bone mass and bone remodeling will be discussed.

Biography

Dr Olga Tsigkou is a Lecturer in Biomaterials (Assistant

Professor) and Programme Director for the MSc in

Biomaterials at the Department of Materials, School of

Natural Sciences, Faculty of Science and Engineering at the

University of Manchester, UK. Her research focuses

predominantly in the application of stem cells, 3D porous

scaffolds and hydrogels on tissue regeneration applications.

She has developed robust protocols for 3D cell culture

models in static and shear stress (bioreactor) culture

conditions. Her research interests include cell-substrate

interactions, vascularization strategies, in vitro tissue

modeling and substrate directed differentiation of stem

cells. She has published highly cited papers on these topics

in leading international journals (e.g. PNAS, Biomaterials,

Advanced Functional Materials and Acta Biomaterialia). Her published work includes more than

30 original research papers in international peer-review journals with over 1200 citations focusing

in the fields of bone tissue engineering, bioactive glasses, vascularization, as well as imaging and

material characterization. Dr Tsigkou has successfully supervised 18 Master students and is

currently involved in the supervision of 6 PhD students and an EPSRC fellow.

‘Mix and match’: local delivery of protein-based biologics

using responsive microgels

Paige LeValley

Centennial Development Professor of Chemical and Biomolecular Engineering, Chemical and

Biomolecular Engineering and Materials Science and Engineering, University of Delaware,

Newark, DE, 19716, USA

Abstract

Protein-based biologics, particularly antibodies, are of growing interest owing to their specificity

and therapeutic efficacy, especially for many conditions that traditionally have been difficult to

treat (e.g., metastatic cancer, misregulated wound healing). The use of multiple therapeutics,

combination therapies, that target different aspects of disease mechanisms can be particularly

effective; however, such therapies have a significant risk of systemic toxicity owing to the high

total doses that must be used. Responsive hydrogels offer a facile platform for the local, controlled

release of these large, hydrophilic proteins for the design of personalized combination therapies

while minimizing adverse side effects. Specifically, in this talk, I report the development of mixed

populations of hydrogel microparticles, or microgels, for achieving tunable and tailorable release

profiles of antibodies in vitro and in vivo. Microgels of uniform size and relevance for local

injection were created using microfluidic devices. To achieve tunable and on-demand release

profiles, microgels that respond to either internal (i.e., reducing microenvironments) or external

(i.e., light) cues were designed. Modular building blocks, multifunctional polymers with a variety

of chemical handles, were used to create mixed populations of microgels that localize to desired

tissues and release multiple therapeutics across a range of time scales.

Nitric Oxide vs Bacteria: NO means NO!

Raechelle A D’Sa

Head of Antimicrobial Biomaterials Group, School of Engineering, University of Liverpool

Brownlow Hill, Liverpool, L69 3GH

Abstract

Nitric oxide (NO) plays a significant role in many biological processes, including the body’s

own immune response to fighting off infections. Given the rise in multi drug resistant bacteria,

conventional antibiotics are failing, which demands the development of new antimicrobial agents

that are not antibiotics. NO holds substantial promise in this regard as it has shown potent

antimicrobial activity against both planktonic and biofilm bacteria and has a low tendency to

develop microbial resistance. NO is a short-lived, lipophilic gas that can easily diffuse across a

cell membrane and combines with reactive oxygen species to cause nitrosative damage on

invading pathogens. The activity of NO is dose dependent with low concentrations dispersing

biofilms and high concentrations having more of a biocidal effect. Despite the potency of NO as

antimicrobial agent, delivery of the gas in a controlled and sustained manner for the desired

clinical application is where the challenge lies. This talk will describe a variety of delivery

platforms that have been developed to provide controlled and sustained delivery for an elongated

lifetime of NO release. The platforms include the hydrogels, nanoparticles, electrospun fibers

and thin film coatings for treatment of dermal, ocular surface or orthopaedic infections.

Biography

Dr. D’Sa’s leads the Antimicrobial Biomaterials Group at

the University of Liverpool. Her research focuses on the

development of nitric oxide delivery platforms for treatment

of multidrug resistant infections. Her research focuses on

the development of these antimicrobial platforms to be used

for skin, ocular and bone tissue engineering applications.

She has over £2 million in research funding with over £1.5

million as a PI. She currently sits on the Editorial Board and

Topic Board for the Journal Polymers and Antibiotics. She

has been the recipient of the Arthur D Chambers and Buhle

Endowment Fellowships. Dr D’Sa is passionate about

supporting the next generation of scientists and has supervised students from various backgrounds

to deliver new solutions for infection control and tissue engineering applications. She is currently

involved with the supervision of 7 PhD students, and 2 postdoctoral fellows. She engages widely

with clinicians, health professionals, patients, charities, has a significant interest in communication

of science to the general public through artistic media.

Engineered microenvironments for stem cell engineering

Manuel Salmeron-Sanchez

Co-Director, Centre for the Cellular Microenvironment; Full Professor of Biomedical

Engineering; University of Glasgow, UK

Abstract

Physical properties of the extracellular matrix (ECM) and the use of growth factors are powerful

tools to control cell behaviour, including stem cell differentiation. Integrins are

mechanotransductors that feel and respond to the viscoelastic properties of the ECM. We have

shown that cells respond to pure viscous interfaces and that results are explained by the classical

clutch model for cell adhesion. At the same time, growth factors are important molecules that

trigger signalling cascades that control e.g osteogenesis and vascularisation. We have developed

material systems that allow simultaneous stimulation of integrins and growth factors receptors. We

have engineered polymers that unfold and assemble fibronectin to allow exposure of the integrin

(FNIII9-10) and growth factor (FNIII12-14) binding regions, leading to highly efficiency

presentation of growth factors, to maximise effects with minimal doses. In parallel, we have also

engineered dynamic systems that allow control over temporal release of adhesion molecules and

growth factors. Unconventionally, we have used non-pathogenic bacteria that have been

engineered to control release of a fribronectin fragment and BMP-2 in a dynamic way. We present

bacteria-based materials in which symbiotic bacteria/mammalian cell interactions occur and their

use for stem cell engineering.

Biography

Prof Manuel Salmeron-Sanchez is co-Director of the Centre

for the Cellular Microenvironment at the University of

Glasgow. He did a PhD in Valencia and postdoctoral work

at the Institute for Macromolecular Chemistry in Prague and

the Katholieke Universiteit Leuven. He was Assistant

Professor at Universitat Politècnica de València, promoted

to Associate Professor in 2008 and Full Professor in 2010.

He did a sabbatical year at the Georgia Institute of

Technology and moved to the University of Glasgow in

2013 as the Chair of Biomedical Engineering. Manuel is a

European Research Council (ERC) investigator. His work

has attracted significant funding from the ERC (PoC, 2

awards) and Research Councils in the UK (MRC) and has set up the basis for a programme of

research to help civilians affected by landmines, funded by the Sir Bobby Charlton Foundation.

Overall, his work spans fundamental mechanisms at the cell/material interface as well as

translational research that has saved from amputation the leg of a first veterinary patient, a dog

called Eva (https://goo.gl/1Z3r8t). He has authored more than 160 papers in major journals

including PNAS, Science Advances, Nature Biomedical Engineering and Advanced Materials. He

has had his research featured in newspapers and TV channels around the world.

Flexible and injectable fibrous scaffolds for the regeneration of pelvic

fractures

Sandra Camarero-Espinosa

MERLN Institute for for Technology-Inspired Regenerative Medicine, Maastricht University,

Maastricht, The Netherlands.

Abstract

Pelvic fractures in the elderly population account for 7% of the total osteoporosis-associated

fractures. Current treatments rely on extensive and invasive surgery and are therefore, not

recommended to elderly patients. Common advice is total rest until natural bone healing occurs,

with the associated development of “dysmobility syndromes” upon long periods of bed

confinement. Bone tissue regeneration with the aid of injectable osteoinductive materials would

avoid invasive surgeries, providing a solution to this problem.

Collagen, the main component of the non-mineralized fraction of bone, and nano-hydroxyapatite

(nHA) have been shown to have beneficial effects on the regeneration of bone, promoting an

enhance mineralized matrix deposition. Similarly, bioactive mesoporous glasses (BMGs) account

for a very high specific surface are (200-500 m2/g) that enhances the deposition of mineralized

matrix. To promote a pro-osteogenic and anti-osteoclastogenic behavior, these materials can be

doped with strontium and selenium. Here, we report on the fabrication of electrospun UV-

crosslinked collagen scaffolds with fiber diameters between 140-180 nm, reinforced with Sr- and

Se-doped nHA and BMGs that are exploited for the regeneration of pelvic bone fractures.

Biography

Sandra Camarero-Espinosa`s research revolves around the

regeneration of complex tissues. The design, synthesis,

fabrication and investigation of novel hierarchical

polymeric bio(nano)materials whose physicochemical

properties can be tuned mimicking nature from the

molecular to the macro scale and, the effect of these ones on

cell phenotype and matrix deposition.

Sandra Camarero-Espinosa was educated at the University

of the Basque Country (Spain) where she obtained her BSc.

degree as Chemical Engineer and M.Sc. in Engineering of

Advanced Materials. Sha developed her doctoral studies at

the Adolphe Merkle Institute (Fribourg, Switzerland) and

was recognized with an award to an outstanding PhD thesis by the Swiss Chemical Society. After

gaining a fellowship from the Swiss National Science Foundation, she moved to Brisbane

(Australia) to work at the Australian Institute for Bioengineering and Nanotechnology. Sandra is

now a post-doctoral researcher at the MERLN institute where she works on the development of

instructive hierarchical biomaterial scaffolds for the regeneration of complex tissues.

The platform of materials and functionalization routes for the

biofabrication of GIOTTO devices

Sonia Fiorilli

Politecnico di Torino, Department of Applied Science and Technologies, Corso Duca degli

Abruzzi 24, Turin, Italy

Abstract

The incidence of osteoporotic fractures is expected to double rapidly due to progressive population

ageing. In this context, the GIOTTO project aims to develop three different devices to treat specific

osteoporosis fractures through the synergistic combination of smart nanomaterials and 3D

fabrication technologies. The three devices will share the use of novel bioactive inorganic phases,

nano-hydroxyapatites and mesoporous bioactive glasses, substituted with biologically active ions

able to stimulate bone production (e.g. Sr2+). The developed inorganic phases will be dispersed in

a resorbable matrix to produce composites with the desired resorption kinetics and matching the

fracture specificities at different body sites. In particular, the bioactive materials will be combined

with the following different matrices:

- an optimised blend of biodegradable polyesters (e.g. PLLA, PCL) to fabricate 3D scaffolds

by extrusion-based printing

- collagen matrix to produce a flexible, fibrous injectable scaffold through electrospinning

- calcium sulphate hemihydrate to produce an injectable resorbable radiopaque cement

GIOTTO materials will be also ad-hoc functionalised through different strategies, with the dual

aim to impart specific properties (e.g. mechanical resistance, degradation kinetics) to the final

devices and to couple them with a novel recombinant biomolecule able to inactivate the osteoclast

activity (ICOS-Fc).

Biography

Sonia Lucia Fiorilli graduated in Industrial Chemistry and took her

PhD in Materials Science and Technology at Politecnico di Torino in

2005. Currently she is Associate Professor at Politecnico di Torino,

where she is lecturer of “Chemistry”, co-lecture of “Physical chemistry

of materials for nanotechnologies”. Her research activity mainly

focuses on the synthesis, characterization and functionalization of

bioceramics, as coatings and 3D scaffolds, for bone and soft tissue

regeneration. More recently, her research interests also include the

design of 3D printed biomimetic scaffolds based on the combination

of collagen and inorganic bioactive phases, properly optimised through

different cross-linking methods.

Prof. Fiorilli is involved in several funded projects as principal investigator or WP/task leader,

including EU-H2020 projects (e.g. EU-H2020- NMBP-22-2018- GIOTTO, EU-H2020-NMP6-

2015 MOZART, MSCA-ITN Action POLYSTORAGE) and national projects (e.g. PI of

ZODIAC “Zwitterionic mesOstructureD glAsses: powerful deviCes for bone regeneration”).

She is currently involved in the supervision/co-supervision of 6 PhD students.

Nanofilled electrospun fibers inspired by elastin and natural polymers

Nicola Ciarfaglia, Antonietta Pepe, Antonio Laezza, Brigida Bochicchio*

Associate Professor of Organic Chemistry; Department of Science; University of Basilicata, Via

Ateneo Lucano 10, Potenza, Italy

Abstract

Electrospinning is an emerging technique with applications in tissue engineering for the high

surface area to volume ratio and the interconnected pores of nanofibers. Blending of synthetic

polymers as polylactic acid (PLA) and poly--caprolactone (PCL), together with natural proteins

(Gelatin, Elastin) were conceived until now in order to obtain scaffolds with combination of

strength and biocompatibility usually used in soft-tissue regeneration. Furthermore, the use of

nanoreinforcements as bioglass and/or nanocellulose is aimed to overcome the limited mechanical

performances of the scaffolds. In this work, we have successfully electrospun highly hydrophobic

(PDLLA) and hydrophilic polymers (gelatin and a human tropoelastin-inspired sequence) together

with bioglass microparticles and crystalline nanocellulose as nanoreinforcements in the

perspective of future applications in hard-tissue regeneration (bone). Additionally, PDLLA was

herein adoperated for its faster degradation times in comparison to the most used PLA. The

matrices were cross-linked in order to confer stability in water. Afterward, the matrices were

tested concerning wettability, swelling and Young's elastic modulus. They show complete

wettability and a significative decrease of Young's Modulus after swelling (comprised between 27

and 23 MPa). The value is analogous to that found for electrospun scaffolds composed of collagen,

elastin and PCL. Funding: PON R&I 2014-2020 (572 PON_ARS01_01081).

Biography

Professor Bochicchio’s research focusses on biopolymers

and peptides inspired by elastomeric proteins for tissue

engineering. Professor Bochicchio has authored 60

international peer-reviewed journal publications and Invited

Speaker at 24 International Meetings. Professor

Bochicchio’s research has been supported by Italian

Ministry of University and European Community and also

attracts interest from multinational industrial partners. To

date, she has secured ≈€1.8M (Co-I) research funding from

National Operational Program "Research and Innovation"

2014-2020 in health sector. Professor Bochicchio has

successfully supervised to completion 2 PhD student and 20

MSc students all of whom have remained in engineering/science and or academia. She is currently

involved in the supervision of 1 PhD student. Additionally, she is currently mentoring one PhD

research fellow.

The Effect of Elastin Degradation Products and Elastin Fibers on COPD and Control Lung Mesenchymal Stromal cells

Willeke F. Daamen* Dept. of Biochemistry, Radboud Institute for Molecular Life Sciences,

Radboud university medical center, Nijmegen, the Netherlands Abstract Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and an irreversible loss of alveolar architecture and extracellular matrix. Novel strategies aimed at the regeneration of the lost alveolar tissue are needed and may include the use of lung mesenchymal stromal cells. These cells produce anti-inflammatory factors, growth factors and extracellular matrix components, including elastin, thereby providing a potential niche for alveolar repair. The reparative capacity of mesenchymal stromal cells from the lungs of COPD patients, however, may be hampered due to oxidative stress and extracellular matrix loss, e.g. by the presence of degradation products of elastic fibers. We investigated whether degradation products of the extracellular matrix, such as hydrolyzed elastin, affect the regenerative capacity of lung mesenchymal stromal cells and whether a supporting micro-environment consisting of intact collagen fibrils and elastin fibers improves the function of lung mesenchymal stromal cells. Biography Willeke Daamen PhD is a scientific researcher at Radboud university medical center. She aims to promote the intrinsic regenerative capacity of patients, mostly by using cell-free biodegradable biomaterials that stimulate the endogenous healing response of tissues. Her group has designed biomaterials that indeed influence infiltrating cells. One example is that the incorporation of solubilized elastin enhances angiogenesis and elastic fiber formation in vivo. Her straightforward biomaterial designs in combination with close collaborations with clinicians, researchers and entrepreneurs will facilitate the translation to the clinic, so that patients will indeed benefit from her research achievements. Willeke Daamen is secretary of the Netherlands Society for Biomaterials and Tissue Engineering (NBTE) and organized and chaired the 10th European Elastin Meeting. She supervised 15 past and present PhD students and has published >95 peer-reviewed papers.

* Full author list: Danique J Hof1, Dennis MLW Kruk2,3, Rob TC Meuwese1, Elly MM Versteeg1, Nick HT ten Hacken3,4, Irene H Heijink2,3,4, Toin H van Kuppevelt1 & Willeke F Daamen1. 1Radboud university medical center, Radboud Institute for Molecular Life Sciences, Dept. of Biochemistry, Nijmegen, The Netherlands 2University of Groningen, University Medical Center Groningen, Dept. of Pathology and Medical Biology, Groningen, The Netherlands 3University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands 4University of Groningen, University Medical Center Groningen, Dept. of Pulmonary Diseases, Groningen, The Netherlands

Polyglycolic acid---an old polymer for new scaffolds and implants

Ying Yang

Professor in Biomaterials and Tissue Engineering; Course director of MSc Biomedical Engineering; School of

Pharmacy and Bioengineering; Keele University, Stoke-on-Trent ST4 7QB; UK

Abstract

Polyglycolide (PGA) is one of the earliest biodegradable polymers explored for biomedical application, date back

1970s for the first synthetic absorbable suture. PGA is highly crystalline polymer, endowing its high tensile modulus.

In addition, PGA’s rapid degradation via bulk hydrolysis makes it as appropriate materials for scaffolds in regenerative

medicine. However, the application of PGA as scaffolds in tissue engineering is hampered by its high crystallinity

(45-55%) property. PGA is insoluble in most organic solvents except the highly toxic solvent, hexafluoroisopropanol.

Currently the practically feasible fabrication technique for porous PGA scaffolds is making PGA nonwoven fibers via

melt-spinning, which has poor compressive properties and difficulty to control porosity, pore size and distribution.

Working with the research partners, we explored a novel fabrication technique, supercritical carbon dioxide (scCO2)

assisted melt-foaming, to generate porous PGA scaffolds. In this talk, the uniqueness of the scCO2 fabrication

processing and the cellular response to the scaffolds will be demonstrated. The comparison study of in vitro and in

vivo degradation and immunoresponse triggered by PGA degraded products will be presented. It is confirmed that

PGA could be explored as unique scaffolds and implants through the new fabrication technique.

Biography

Dr Ying Yang is a Professor in biomaterials and tissue engineering. Her

main research interests/activities are the design and fabrication of

biomaterials to provoke desired cellular response at materials and cell

interface including bioactive scaffolds for tissue engineering,

anticoagulant surface for implanted biosensor, and the bioorganic metal

surface for anti-fouling application. She has established systematic

study methods including smart nanofiber applications, detection of

variation of cell adhesion capacities and structures of collagen based

matrices, in order to develop new strategies in regenerative medicine

and clinical diagnostics. She has undertaken diverse clinical projects from colony growth of stem cells as a diagnosis

assay for osteogenic potency assessment, pathological calcification of heart valves, the relation of pelvic organ

prolapse and ageing, cartilage/blood vessel regeneration, eye models (glaucoma and retina) to pseudoislets generation.

She also heavily engages in development of non-destructive and on-line monitoring systems for tissue engineering

products and diagnostics. As the PI and co-PI, her research has been financially supported by BBSRC, EPSRC,

European frame work FP5-7 and various charity. She has published over 130 full peer-reviewed papers, 11 chapters

in books and filed 5 patents.