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HighlightsA compilation of the best articles published within the last two years

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Biomedical MaterialsMaterials for tissue engineering and regenerative medicine

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Biomedical Materials

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ISSN 1748-6041

BIOMEDICAL MATERIALS

Materials for t issue engineering and regenerative medicine

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Featured papersCharacterization of a biodegradable coralline hydroxyapatite/calcium

carbonate composite and its clinical implementation Kun Fu, Qingguo Xu, Jan CzernuszKa, James T TriFFiTT and zhidao Xia

Electrospun silk-elastin-like fibre mats for tissue engineering applicationsraul maChado, andré da CosTa, ViTor senCadas, Carmen garCia-aréValo,

Carlos m CosTa, Jorge Padrão, andreia gomes, senenTXu lanCeros-méndez, José Carlos rodríguez-Cabello and margarida Casal

Volume 8 Number 6 December 2013


http://cms.iopscience.org/3205ba4f-d278-11e1-9b7a-4d5160a0f0b4/index.html


iopscience.org/bmm 3

This Biomedical Materials (BMM) “Highlights” is being published once again to put a spotlight on a selection of papers published in the last year or so: the latest “Editors’ Pick” articles; some of the articles selected for the “2013 Highlights”; selected articles from 2014; an editorial on tissue engineer’s toolbox; and the “BMM interviews”. In this one publication are papers dealing with scientific inquiry, engineering advances, and ideas, and the people behind them. Bringing these articles together in this highlighted publication may draw your attention to read a paper that slipped past you in its regular journal issue, or to look through a paper for a second time. The juxtaposition of the works may elicit thoughts about the connectedness of ideas and scientific and engineering possibilities, and may spur you to think about old ideas in a new light.

The papers in the Highlights have been selected based on their novelty and readership interest, reflected in the number of downloads. They demonstrate the quality and the range of compelling studies that fall into the scope of BMM.

As we proceed into the 9th volume of BMM we can reflect on the changes that the field has seen since the first papers were published in volume 1 in 2006. Nine years is a long time when measured as research years. There have been many new biomaterials developed and evaluated and new medical devices introduced into clinical use, new insights into the biological response to materials, and an array of stem and progenitor cells qualified for the treatment of many clinical problems.

For example, the past nine years has seen the development of certain classes of polymeric compounds with unique properties, including: those capable of safely undergoing covalent cross-linking in vivo; thixotropic (shear thinning) materials; and cryogels. These advances have enabled the development of injectable matrices for the treatment of small defects (down to less than 10 mm3) contained within otherwise healthy tissue. As regards our understanding of the biological response to materials, up until 2006 the ubiquitous macrophage found around implants was generally treated as a single cell population. But as the years progressed, it became clear that there were, in fact, two macrophage phenotypes, M1 and M2, with very different behaviours. In just the past few years, that same duality of function appears to also apply to the neutrophil, as investigators are distinguishing N1 and N2 phenotypes. In the coming years, we are sure to be seeing in this journal advances in the applications of biomedical materials based on these cell biological discoveries.

And the past nine years have witnessed the preparation of several types of stem and progenitor cells, qualified for human use. For example, clinical trials have employed autologous and allogeneic marrow stromal (mesenchymal stem) cells in the treatment of cardiac and other clinical problems, and human embryonic stem-cell-derived retinal pigment epithelial cells for the treatment of certain retinal diseases. Other studies have demonstrated improved outcomes when the cells were delivered in a biomaterial matrix. This journal will likely be seeing more of such investigations in the years ahead.

The journal continues to encourage the submission of in vitro and in vivo investigations of biomedical materials and medical devices, and results from human trials. And we hope that some of your articles will be included in future issues.

In-Seop Lee and Myron SpectorEditors-in-Chief

Welcome

In-Seop LeeYonsei University, Seoul, Korea

Myron SpectorHarvard Medical School, VA Boston Healthcare System, MA, USA

Biomedical MaterialsBiomedical Materials

4 iopscience.org /bmm

ContentsEditorial board 5

BMM interviews 6

Selected articles from 2014 7

Highlights of 2013 10

Editors’ pick articles 14

Biomedical Materials: Materials for tissue engineering and regenerative medicine publishes original research findings that contribute to our knowledge about the composition, properties and performance of materials for tissue engineering and regenerative medicine.

Typical areas of interest include: • Synthesis/characterization of biomedical materials• In vitro/in vivo performance of biomedical materials• Nature-inspired synthesis/biomineralization• Tissue engineering/regenerative medicine applications• Interaction of molecules/cells with materials• Effects of biomaterials on stem cell behaviour • Growth factors/genes incorporated into biomaterials

JOURNAL SCOPE

Cover image: Hematoxylin-eosin-stained microscope image of regenerated bone within CB-HAp-implanted defects two weeks post-implantation Beom-Su Kim et al 2014 Biomed. Mater. 9 025004.

All of the articles featured in this brochure are available at iopscience.org/bmm




Editorial boardEditors-in-ChiefI-S Lee Yonsei University, Seoul, Korea M Spector Harvard Medical School, VA Boston

Healthcare System, MA, USA

Editorial boardL Ambrosio National Research Council of Italy, Naples, ItalyD G Anderson Massachusetts Institute of Technology, Cambridge, MA, USAK Anseth University of Colorado at Boulder, CO, USAA Atala Wake Forest University, Winston-Salem, NC, USAB Ben-Nissan University of Technology Sydney, AustraliaJ A Burdick University of Pennsylvania, Philadelphia, USAY Cao Shanghai Jiao Tong University, ChinaA Ito National Institute of Advanced Industrial Science and Technology, Tsukuba, JapanA Khademhosseini Harvard Medical School, Cambridge, MA, USAC J Kirkpatrick Johannes Gutenberg University, Mainz, GermanyS C Kundu Indian Institute of Technology, Kharagpur, IndiaT Kyriakides Yale University, New Haven, CT, USA

P Layrolle Nantes University, FranceS Liao National University of Singapore, SingaporeW Liu Shanghai Jiao Tong University, People’s Republic of ChinaE G Loboa North Carolina State University, NC, USAY Luo Peking University, Beijing, People’s Republic of ChinaI Noh Seoul National University of Science and Technology, KoreaT Okano Tokyo Women’s Medical University, JapanJ-C Park Yonsei University, Seoul, KoreaH Redl Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, AustriaM Shoichet University of Toronto, ON, CanadaE Tanner University of Glasgow, UKA Weiss University of Sydney, AustraliaJ Werkmeister CSIRO Molecular and Health Technologies, Clayton, AustraliaH-C Yang Seoul National University, KoreaS M Zhang Huazhong University of Science and Technology, Wuhan, People’s Republic of China

Our dedicated Biomedical Materials team at IOP Publishing is here to ensure that the peer-review and production processes run as smoothly as possible for our authors.

JOURNAL TEAM

Robert OllerenshawPublishing Administrator

Paul MacBeathPublishing Editor

Antigoni MessaritakiPublisher

Caitlin HesserProduction Editor

Zoe AndersonSenior Marketing Executive



An interview with I V Yannas Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA Tracing one of the deepest roots of biomaterials in tissue engineering/regenerative medicine.2013 Biomed. Mater. 9 040401.

BMM interviews

To read the interviews go to iopscience.iop.org/bmm/page/Interviews

A new feature for the journal, the BMM interviews feature leaders in the field of biomaterials in conversation with Professor Myron Spector.

An interview with Jackie Yi-Ru YingInstitute of Bioengineering and Nanotechnology, Singapore The compleat multi-tasker. 2014 Biomed. Mater. 9 030401.

An interview with Molly S ShoichetDonnelly Centre for Cellular & Biomolecular Research, University of Toronto, ON, Canada Developing biomaterials and mobilizing resources for assaults on some of the most devastating medical problems.2013 Biomed. Mater. 8 060401.

http://iopscience.iop.org/1748-605X/8/4/040401

http://iopscience.iop.org/1748-605X/page/Interviews





The tissue engineer’s toolbox manifesto

Myron Spector

2014 Biomed. Mater. 9 010201

Patients have benefited greatly from the steady stream of new medical devices approved each year by the US Food and Drug Administration and by regulatory agencies in countries around the world. But the number of such devices for tissue engineering and regenerative medicine is just a small fraction of these, perhaps 7 of the 194 devices (<5%) approved by the FDA since 2008. Few new tissue engineering and regenerative medicine devices have reached the clinic despite the proliferation of biomaterial matrices/scaffolds, cells, and regulators of cell function (e.g., growth factors); i.e., the three types of tool currently available for implantation or injection into a specific type of defect to facilitate regeneration (the paradigm of regenerative medicine), or for the formation of tissues and organs in vitro for subsequent implantation (the tissue engineering plan). While the number of new tools added to the tissue engineer’s toolbox each year is continuing to grow dramatically, there are few tools being implemented for the production of new medical devices undergoing human trial. What are the bottlenecks in getting the tools out of the toolbox and into clinical use to advance patient care?

Construction of a bFGF-tethered multi-functional extracellular matrix protein through coiled-coil structures for neurite outgrowth induction

Masayasu Mie, Shoichi Sasaki and Eiry Kobatake

2014 Biomed. Mater. 9 015004

In this study, an artificial multi-functional extracellular matrix (ECM) protein, tethered with a growth factor, was developed for neurite outgrowth induction. The designed ECM protein was comprised of an elastin-like peptide, as a structural unit, as well as the AG73 peptide sequence derived from the laminin and the C3 peptide sequence, which binds to neural cell adhesion molecules (derived from a synthetic peptide library) as functional units. Both AG73 and C3 have been demonstrated to promote cell adhesion and enhance neurite outgrowth. For the tethering of basic fibroblast growth factor (bFGF) to the ECM protein, helical peptides were fused to the ECM protein to form a coiled-coil helical structure with helical peptide-fused bFGF. Neurite outgrowth was induced in the PC12 cells that were cultured on this ECM protein as a result of the tethered-bFGF. Moreover, neurite outgrowth was enhanced by the AG73 and C3 peptides of the ECM protein.

Selected articles from 2014

Myron Spector

Masayasu Mie

Eiry Kobatake


http://iopscience.iop.org/1748-605X/9/1/015004/article



SELECTED ARTICLES FROM 2014

Shunying Liu

‘Smart’ gold nanoshells for combined cancer chemotherapy and hyperthermia

Zhongshi Liang, Xingui Li, Yegui Xie and Shunying Liu

2014 Biomed. Mater. 9 025012

Nanomaterials that circulate in the body have great potential in the diagnosis and treatment of diseases. Here we report that ‘smart’ gold nanoshells can carry a drug payload, and that their intrinsic near-infrared (NIR) plasmon resonance enables the combination of chemotherapeutic and hyperthermia therapies. The ‘smart’ gold nanoshells (named DOX/A54@GNs) consist of (a) gold nanoshells (GNs) with NIR plasmon resonance, which not only act as nanoblocks but also produce local heat to allow hyperthermia; (b) an anticancer drug, doxorubicin (DOX), which was conjugated onto the nanoblocks by pH-dependent biodegradable copolymer thiol poly(ethylene glycol) derivatives via carbamate linkage; and (c) the targeting peptide A54 (AGKGTPSLETTP) to facilitate its orientation to liver cancer cells and enhance cellular uptake. The conjugated DOX was released from the DOX/A54@GNs much more rapidly in an acidic environment (pH 5.3) than in a neutral environment (pH 7.4), which is a desirable characteristic for intracellular tumor drug release. DOX-modified GNs showed pH-dependent release behavior, and the in vitro cell uptake experiment using ICP-AES and microscopy showed greater internalization of A54-modified GNs in the human liver cancer cell line BEL-7402 than of those without A54. Flow cytometry and fluoroscopy analysis were conducted to reveal the enhanced cell apoptosis caused by the A54-modified GNs under combined chemotherapeutic and hyperthermia therapies. These results imply that DOX/A54@GNs could be used as a multifunctional nanomaterial system with pH-triggered drug-releasing properties for tumor-targeted chemotherapy and hyperthermia.




Comparison of in vitro and in vivo bioactivity: cuttlefish-bone-derived hydroxyapatite and synthetic hydroxyapatite granules as a bone graft substitute

Beom-Su Kim, Hyo Jin Kang, Sun-Sik Yang and Jun Lee

2014 Biomed. Mater. 9 025004

Bone reconstruction in clinical settings often requires bone substitutes. Hydroxyapatite (HAp) is a widely used bone substitute due to its osteoconductive properties and bone bonding ability. The aim of this study was to evaluate HAp granules derived from cuttlefish bone (CB-HAp) as a substitute biomaterial for bone grafts. In this study, HAp granules were prepared from raw CB by using a hydrothermal reaction. The formation of HAp from CB was confirmed by scanning electron microscopy and x-ray diffraction analysis. The bioactivity of the CB-HAp granules was evaluated both in vitro and in vivo. Our results show that CB-HAp is non-toxic and that CB-HAp granules supported improved cell adhesion, proliferation and differentiation compared to stoichiometric synthetic HAp granules. Furthermore, in vivo bone defect healing experiments show that the formation of bone with CB-HAp is higher than that with pure HAp. These results show that CB-HAp granules have excellent potential for use as a bone graft material.

SELECTED ARTICLES FROM 2014

Jun Lee

Bioactive glass/ZrO2 composites for orthopaedic applications

D Bellucci, A Sola and V Cannillo

2014 Biomed. Mater. 9 015005

In the present research, the promising properties of the new BG_Ca–K glass, with its low tendency to crystallize and high apatite-forming ability, allowed us to sinter the composites at a relatively low temperature with excellent effects in terms of bioactivity. In addition, it was possible to benefit from the good mechanical behaviour of Y-TZP, thus obtaining samples with microhardness values that were among the highest reported in the literature. After a detailed analysis regarding the thermal behaviour of the composite powders, the sintered bodies were fully characterized by means of x-ray diffraction, SEM equipped with EDS, density measurements, volumetric shrinkage determination, mechanical testing and in vitro evaluation in a simulated body fluid (SBF) solution. According to the experimental results, the presence of Y-TZP improved the mechanical performance. Meanwhile, the BG_Ca–K glass, which mainly preserved its amorphous structure after sintering, provided the composites with a good apatite-forming ability in SBF.

Devis Bellucci





Decellularization for whole organ bioengineering

J E Arenas-Herrera, I K Ko, A Atala and J J Yoo

2013 Biomed. Mater. 8 014106

Organ transplantation in an orthotopic location is the current treatment for end-stage organ failure. However, the need for transplantable organs far exceeds the number of available donor organs. As a result, new options, such as tissue engineering and regenerative medicine, have been explored to achieve functional organ replacement. Although there have been many advances in the laboratory leading to the reconstruction of tissue and organ structures in vitro, these efforts have fallen short of producing organs that contain intact vascular networks capable of nutrient and gas exchange and are suitable for transplantation. Recently, advances in whole organ decellularization techniques have enabled the fabrication of scaffolds for engineering new organs. These scaffolds, consisting of naturally-derived extracellular matrix (ECM), provide biological signals and maintain tissue microarchitecture, including intact vascular systems that could integrate into the recipient’s circulatory system. The decellularization techniques have led to the development of scaffolds for multiple organs, including the heart, liver, lung and kidney. While the experimental studies involving the use of decellularized organ scaffolds are encouraging, the translation of whole organ engineering into the clinic is still distant. This paper reviews recently described techniques used to decellularize whole organs such as the heart, lung, liver and kidney and describes possible methods for using these matrices for whole organ engineering.

Highlights of 2013

James J Yoo

Characterization of a biodegradable coralline hydroxyapatite/calcium carbonate composite and its clinical implementation

Kun Fu, Qingguo Xu, Jan Czernuszka, James T Triffitt and Zhidao Xia

2013 Biomed. Mater. 8 065007

A partially converted, biodegradable coralline hydroxyapatite/calcium carbonate (CHACC) composite comprising a coral calcium carbonate scaffold enveloped by a thin layer of hydroxyapatite was used in the present study. The CHACC was characterized using powder x-ray diffraction, scanning electron microscopy and energy dispersive x-ray spectroscopy. The ability of the CHACC to promote conductive osteogenesis was assessed in vitro using human mesenchymal stem cells (hMSCs) and in vivo using an immunodeficient mouse model. The clinical performance of CHACC as a bone substitute to fill voids caused by excision of bone tumours was also observed in 16 patients.





HIGHLIGHTS OF 2013

The CHACC was found to consist of two overlapping layers both morphologically and chemically. Hydroxyapatite formed a thin layer of nanocrystals on the surface and a thick rough crystal layer of around 30 µm in thickness enveloping the rock-like core calcium carbonate exoskeletal architecture. hMSCs cultured on CHACC in osteogenic medium demonstrated significant osteogenic differentiation. After subcutaneous implantation of CHACC incorporating osteogenically differentiated hMSCs and an anti-resorptive agent, risedronate, into an immunodeficient mouse model, bone formation was observed on the surface of the implants. Clinical application of CHACC alone in 16 patients for bone augmentation after tumour removal showed that after implantation, visible callus formation was observed at one month and clinical bone healing achieved at four months. The majority of the implanted CHACC was degraded in 18–24 months. In conclusion, CHACC appears to be an excellent biodegradable bone graft material. It biointegrates with the host, is osteoconductive, biodegradable and can be an attractive alternative to autogenous grafts.

Hydrophilization of synthetic biodegradable polymer scaffolds for improved cell/tissue compatibility

Se Heang Oh and Jin Ho Lee

2013 Biomed. Mater. 8 014101

Porous scaffolds have been widely used in tissue engineering because they can guide cells and tissues to grow, synthesize extracellular matrix and other biological molecules, and facilitate the formation of functional tissues and organs. Although various natural and synthetic biodegradable polymers have been used to fabricate the scaffolds, synthetic polymers have been more widely used for scaffolds since they have good mechanical strength, reproducible/controllable mechanical-chemical properties, and controllable biodegradation rates. However, the ‘hydrophobic character’ of common synthetic polymers is considered a limitation for tissue engineering applications because it can lead to a low initial cell seeding density, heterogeneous cell distribution in the scaffold, and slow cell growth due to insufficient absorption/diffusion of cell culture medium into scaffold and lack of specific interaction sites with cells. The hydrophilization of porous synthetic polymer scaffolds has been considered as one of the simple but effective approaches to achieve desirable in vitro cell culture and in vivo tissue regeneration within the scaffolds. In this review paper, representative synthetic biodegradable polymers and techniques to fabricate porous scaffolds are briefly summarized and their hydrophilization techniques to improve cell/tissue compatibility are discussed.

Jin Ho Lee



HIGHLIGHTS OF 2013

Effect of polyurethane scaffold architecture on ingrowth speed and collagen orientation in a subcutaneous rat pocket model

E L W de Mulder, G Hannink, N Verdonschot and P Buma

2013 Biomed. Mater. 8 025004

Clinically used scaffolds are suboptimal in regenerating the highly oriented meniscus fiber structure in full meniscal defects. The objective of this study was to test whether anisotropic porous scaffolds with channels resulted in a more meniscus like matrix organization compared to isotropic porous scaffolds. Isotropic polyurethane scaffolds were made via standard solvent leaching techniques. Anisotropic porous scaffolds with channels were made via modified thermal induced phase separation. Both scaffold types were analyzed with light microscopy, scanning electron microscopy and computed nano-tomography. Finally, isotropic and anisotropic scaffolds were bilaterally and subcutaneously implanted on the back of 32 Wistar rats for 1, 4, 8 and 24 weeks to assess tissue ingrowth and matrix organization. Isotropic scaffolds had a pore diameter of 35 ± 14.7 µm and a degree of anisotropy of 0.18, while anisotropic scaffolds had a channel diameter of 20 ± 6.0 µm and a degree of anisotropy of 0.39. After implantation full tissue ingrowth was achieved after 8 and 24 weeks for isotropic and anisotropic, respectively. Isotropic scaffolds had a random tissue infiltration with unorganized collagen deposition, whereas anisotropic scaffolds showed tissue infiltration and collagen alignment in the direction of the channels. Anisotropic scaffolds resulted in a matrix organization that resembled the tissue in the vascularized zone of the meniscus, while isotropic scaffolds resembled the tissue in the avascular zone of the meniscus.




For more information and to view the full collection visit ioppublishing.org/books

IOP Expanding PhysicsTM

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A Short Course on Relativistic Heavy-Ion CollisionsAsis Chaudhuri


RenewablesA review of sustainable energy supply options

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SemiconductorsBonds and bands

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The EmbeddingMethod for Electronic StructureJohn E Inglesfield


Vignettes from General RelativityBeverly K Berger


Physics ofthe AtmosphereRodrigo Caballero


Dynamical Propertiesin Nanostructuredand Low-DimensionalMaterialsMichael G Cottam


Principles of Fourier OpticsRobert K Tyson

IOP Concise Physics A Morgan & Claypool Publication

Molecular Photophysics and SpectroscopyDavid L Andrews


An Introduction to Liquid Crystals through ExperimentsMojca ̆Cepic̆


Capture and Relaxation in Semiconductor Quantum DotsR FerreiraGérald Bastard

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http://ioppublishing.org/publications/books



Effective tuning of ligand incorporation and mechanical properties in visible light photopolymerized poly(ethylene glycol) diacrylate hydrogels dictates cell adhesion and proliferation

Michael V Turturro, Sonja Sokic, Jeffery C Larson and Georgia Papavasiliou

2013 Biomed. Mater. 8 025001

Georgia Papavasiliou’s introduction This paper focuses on a detailed experimental sensitivity analysis and identifies the key polymerization conditions that result in significant changes in both the elastic modulus and the immobilized cell adhesion ligand concentration (YRGDS) within visible light photopolymerized PEGDA hydrogels. Among the polymerization conditions

Georgia Papavasiliou

Electrospun silk-elastin-like fibre mats for tissue engineering applications

Raul Machado, André da Costa, Vitor Sencadas, Carmen Garcia-Arévalo, Carlos M Costa, Jorge Padrão, Andreia Gomes, Senentxu Lanceros-Méndez, José Carlos Rodríguez-Cabello and Margarida Casal

2013 Biomed. Mater. 8 065009

Raul Machado’s introduction This work reports the fabrication of recombinant silk-elastin-like proteins (SELPs) fibre mats by electrospinning and the evaluation of their properties and potential use for tissue engineering. In this paper we demonstrate that size and morphology of the electrospun structures are tuned with SELP concentration and type of solvent used, and further stabilized with methanol-saturated air. Human skin fibroblasts were cultured on electrospun fibre mats for assessment of their in vitro performance, revealing suitable properties for application as wound dressing materials in skin regeneration. Future work We plan to further investigate the cell adhesion mechanisms and the 3D spatial distribution of fibroblasts interacting with these materials. Following this characterization, the feasibility of using these materials as wound dressings will be evaluated in vivo.

Editors’ pick articles

Raul Machado

Find out what the authors of selected articles published in the journal have to say about their work, iopscience.iop.org/bmm/page/Editors pick



http://iopscience.iop.org/1748-605X/page/Editors%20pick



investigated, we show that single as well as simultaneous variations in the comonomer, N-vinylpyrrolidinone (NVP), and precursor concentrations of the YRGDS containing PEG monoacrylate macromer result in a broad range of hydrogel elastic modulus and immobilized YRGDS surface concentration in the scaffolds. Increasing the YRGDS surface concentration was shown to enhance fibroblast cell adhesion and proliferation for a given stiffness, while increases in hydrogel elastic modulus was found to decrease cell adhesion and increase proliferation. This illustrates how the appropriate selection of polymerization conditions is critical in fine-tuning cell-biomaterial interactions. Future work We have developed a computational model of hydrogel crosslinking that enables us to track hydrogel properties (i.e. hydrogel crosslink density, gel fraction, and incorporated levels of embedded biofunctionality) dynamically over time for this crosslinking system. We are currently in the process of validating our computational model with the experimental data presented in this manuscript. This model will be useful for guiding the experimental design of PEG scaffolds with desired material properties and immobilized concentrations of multiple biofunctional cues and in the optimization of cell-biomaterial interactions while minimizing the experimental parameter space in achieving these goals. Our current efforts focus on using these engineering approaches to design hydrogels for applications in wound healing, neovascularization of engineered tissues and drug delivery.

EDITORS’ PICK ARTICLES

A biomimetic physiological model for human adipose tissue by adipocytes and endothelial cell cocultures with spatially controlled distribution

Rui Yao, Yanan Du, Renji Zhang, Feng Lin and Jie Luan

2013 Biomed. Mater. 8 045005

Rui Yao’s introduction This 3D multicellular model showed a mutual-enhanced effect between human adipocytes and endothelial cells, which recapitulated the close correlation of adipose tissue development and angiogenesis in native human adipose tissue. On the other hand, traditional 2D coculture showed inhibited adipocyte function and endothelial cell proliferation without a mutual-enhanced effect between adipocytes and endothelial cells. Future work Based on this multicellular model, we are exploring 3D pathological models for diabetes studies and therapy development.

Rui Yao





EDITORS’ PICK ARTICLES

Fabrication and characterization of multiscale electrospun scaffolds for cartilage regeneration

Erica J Levorson, Perumcherry Raman Sreerekha, Krishna Prasad Chennazhi, F Kurtis Kasper, Shantikumar V Nair and Antonios G Mikos

2013 Biomed. Mater. 8 014103

Erica Levorson’s introduction We wished to take previously investigated methods for electrospinning microfibers as well as nanofibers separately and manipulate the fabrication techniques in an effort to develop a seamless method for generating electrospun fibrous mats composed of both micro- and nanofibers mixed throughout the entire scaffold. To accomplish this, we adapted a method previously used at the Amrita Center for fabricating aligned electrospun nanofibers by greatly reducing the speed of the rotating mandrel as well as enabling electrospinning from opposing sides. In doing this, we were able to successfully create scaffolds with micro- and nanofibers well mixed throughout. Moving forward, we showed that this technique can also be used to generate scaffolds composed of two very different fiber materials in addition to different fiber scales. The multiscale scaffolds were then evaluated in vitro and found to be successful in maintaining cellularity under serum-free conditions as well as aid extracellular matrix deposition. Future work Further efforts must be made to better tune the ratio of microfibers to nanofibers in an effort to achieve optimal cellular responses as seen by cellularity and extracellular matrix production.

Erica J Levorson


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