Scaffold for Tissue Engineering

& Regenerative Medicine

Mohamed Labadi

April 9, 2015

Overview

Regenerative Medicine

Tissue Engineering

Scaffolds for TE

Nanotechnology and Microfluidics for Scaffold TE

R&D Trends & Pioneering

Future and Conclusion

Nature Nanotechnology, January 2011

Characterizing Regenerative Medicine

1. Regenerative medicine is a broad definition for innovative medical therapies that will enable the body to repair, replace, restore and regenerate damaged or diseased cells, tissues and organs. (Mayo Clinic)

2. Tools and Procedures (Biofabrication or Additive Manufacturing) of Regenerative Medicine

• Tissue Engineering: Tissue Repair/Replacement and Lab Grown Organs

• Technologies Stem cells Natural and Synthetic Scaffolds 3-D Printing and Chip Technologies

Areas of Regenerative Medicine

1. Artificial Organs: Medical Devices

(Lab Grown Bladder)

2.Tissue Engineering & Biomaterials

Scaffolds

Areas of Regenerative Medicine

3. Cellular Therapies• Use of Stem Cells (From Patient)• Development of Regenerative

Medicine Treatments.• Enhance Regeneration of Tissues

and Organs.

4. Clinical Trials• Many Currently in Progress.• NIH and Private Organizations.

“Body Builders”: The Emerging Science of Regenerative

Medicine

The Beginning………Joseph Vacanti* & Robert Langer** (1993)

——————— Langer R1, Vacanti JP., Tissue engineering, Science,

1993

* Harvard Stem Cell Institute

** Massachusetts Institute of Technology (MIT)

Why Tissue Engineering

• TE is an interdisciplinary field that applies the principles of engineering and the life sciences towards the development of biological substitutes that restore, maintain, or improve tissue function

• Developing living tissue using cells, biomaterials, and signaling molecules

Need for Replacement

• Skin - 3 million procedures per year• Bone - 1 million procedures per year• Cartilage - 1 million procedures per year• Blood Vessel - 1 million procedures per year• Kidney - 600 thousand procedures per year• Liver - 200 thousand procedures per year• Nerve - 200 thousand procedures per year

Why Tissue Engineering

• Traditional Implants (hip replacement…)– Poor biocompatibility– Mechanical Failure (undergo fatigue, wear,

corrosion)• Transplants

– Rejection– Disease transmission– Supply << Demand

3 Tools of Tissue Engineering

• Cells– Living part of tissue– Produces protein and provides function of cells– Gives tissue reparative properties

• Scaffold– Provides structural support and shape to construct– Provides place for cell attachment and growth– Usually biodegradable and biocompatible

• Cell Signaling– Signals that tell the cell what to do– Proteins or Mechanical Stimulation

Components of a TE construct

• Isolated cells and cells substitues Allows for an infusion of specific cells into the patient

without the complication of surgery

• Tissue growth factor Massive quantities in targeted delivery Use of gene delivery system to upregulate the local

production

• Cell-matrix interaction with Scaffolds To grow and eventually replace a biodegradable

scaffold

Strategies of TE

What do we want in a scaffold?

• 1. Biocompatible• 2. Biodegradable• 3. Chemical and Mechanical Properties• 4. Proper architecture

Role of the Scaffold

• Present a surface/structure that closely resembles the extracellular matrix (ECM)

• Surfaces that could maximize favorable biological responses (cell-matrix interaction, Protein-matrix interaction)

Synthetic Scaffolds

[Lecture: Sangeeta Bhatia – ‘Tiny Technologies’ and Regenerative Medicine: stemcellassays.com/2011/04/lecture-sangeeta-bhatia-tiny-technologies-and-regenerative-medicine/]

Natural Scaffolds

Ott HC et al., Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart, Nature Medicine, 2008

Nanotechnology and Microfluidics in Tissue Engineering

• Advances in fabrication technologies have brought a new dimension to the field of tissue engineering.

• Fabricate tissue engineering scaffolds with complex 3-D architectures and customized chemistries that mimic the in vivo tissue environment.

Microfluidic scaffold for tissue engineering

• Application of microfabrication and BioMEMS technology

• Focused toward developing microfluidic networks with geometries that simulate specific cellular networks• Attractive because of ability to produce structures with feature resolution of less than 10 microns• Vascular tissue engineering

• Problems of nutrient transport is critical in the design of tissue engineering

• Scaffolds that are targeted for the growth of complex organs such as the liver and kidney

• Approach to solving this problem involves the integration of an intrinsic vascular network within these scaffolds.

• Drug delivery/ high throughput screening

Microfluidic scaffold for tissue engineering

Regenerative Medicine Challenges

1. Design of Biomaterials that Function in the Body

2. Getting Enough Cells and Cell Types for Engineering Tissues and Organs

3. Vascularity: Engineering Blood Vessels that Supply Nutrients, Oxygen and Signals to Bioengineered Tissues and Organs

4. Cost of Tissue and Organ Development Procedures

Challenge of Regenerative Medicine

Bioengineering of Organs

Ott HC et al., Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart, Nature Medicine, 2008

Potential of Regenerative Medicine

Chip Technology

[Geraldine Hamilton, Body parts on a chip, TEDx Boston, June 2013: https://youtu.be/CpkXmtJOH84]

• Reduces Need for Animal Testing• 3-D Printed Organs on Chips Used to Test Vaccines

3-D Elastic Membrane Fits Heart’s Epicardium

3-D Printer Creates Heart Membrane

[Prof. Igor Efimov, Washington University in St. Louish: ttps://news.wustl.edu/news/Pages/26554.aspx]

Lizhi Xu and al., Nature Communications, 2014, 3329, doi:10.1038/ncomms4329

Promise of Regenerative Medicine

R&D Trends, Innovation and Pioneering

[Laboratory for Multiscale Regenerative Technologies: https://lmrt.mit.edu/research]

Regenerative Medicine Pioneers

Wake Forest Institute for Regenerative Medicine (WFIRM)

Dr. Anthony Atala

• 2006-2007: First to Engineer/Transplant Lab-Grown Organ into a Human

• Transplant was Successful• Currently Developing Organ on a Chip Program

1993: Dr. Robet Langer (Langer Lab, MIT)

Tissue engineering, controlled release systems and transdermal delivery systems

Regenerative Medicine Pioneers

Dr. Paolo Macchiarini (Karolinska Institute)

• 2008: Implanted World’s First Donor Trachea• Recipient: Claudio Castillo• Survived Procedure — Now Has Normal Respiratory Function

Regenerative Medicine Pioneers

Dr. Ali Khademhosseini (Wyss Institute at Harvard)

[MIT Technology Review: www2.technologyreview.com/tr35/profile.aspx?TRID=610]

• 2007: Creating living tissues• Organs in the lab

Regenerative Medicine Pioneers

McGowan Institute of Regenerative Medicine (University of Pittsburg)

Dr. Stephen Badylak• Removed Cells from Pig Bladder Extra Cellular Matrix (ECM)• Re-grows Severed Digits and• New Muscle Tissue Development of 3-D

bioscaffolds for liver and heart regeneration

Regenerative Medicine Pioneers

Regenerative Medicine Innovators

Dr. Geraldine Hamilton (Wyss Institute, Harvard)

2011: Organ on a Chip Technology(Drug Testing Tool)

Regenerative Medicine Innovators

Dr. Sangeeta Bhatia, The David H. Koch Institute for Integrative Cancer Research

• 2003: Uses microchip-manufacturing tools to build artificial livers • Leveraging miniaturization tools from the world of semiconductor

manufacturing to impact human health

Regenerative Medicine Innovators

Dr. Jordan Miller (Rice University)• 2013: Uses 3-D Print Technology• Engineers Blood Vessels Using Sugar

Regenerative Medicine Innovators

Dr. Ramille N. Shah (Northwestern Univ.)• 2011: Leader in Field of 3D-Printable Materials• Engineers new 3D-Inks• Creates Porous Scaffolds• Technique: Additive Manufacturing

(Nanofiber Scaffold For

Cartilage Regeneration)

[Center for Regenerative Nanomedicine, Northwestern University: rn.northwestern.edu/projects/peptide-amphiphile-polymer-hybrids-articular-cartilage-

regeneration]

Peptide amphiphile nanofiber hybrid scaffolds will be created using 3D bioprinting technology

The Business of Regenerative Medicine

Organovo3-D Bioprinting CompanyStarted A Collaboration with NIH (January 2014)Goal: Bioprinting of 3D Living Tissues • Eliminate Challenges to New Therapy

Development• Animal Models: Poor Predictors of Drug Efficacy

and Toxicity

The Business of Regenerative Medicine

TengionA Biotechnology Company Company Platform for Engineering

Tissues/Organs Organ Regeneration Processo Doctors send Tissue Sample from Diseased or

Failing Organ to Tengiono Tengion Selects and Multiplies Healthy Cellso Place Cells on an Organ-Shaped Scaffoldo Result: A Neo-Organ for Transplant

Futuristic!

Stem Cells + Organ Scaffold + 3D Printer

= Libraries of Replacement Organs?

Conclusion

• Engineered tissue replacements combine celles & biomaterials to replace a subset of tissue functions

• Biomaterials are natural or synthetic• Convergence of cell biology,

medicine, and angineering is advancing the field

• Langer R1, Vacanti JP., Tissue engineering, Science, May 1993• K. Ren, Y. Chen, H. Wu, New materials for microfluidics in biology, Current Opinion in Biotechnology Volume

25, 2014• Ott HC et al., Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial

heart, Nature Medicine, 2008• Sala et al., Current Applications of Tissue Engineering in Biomedicine, J Biochip Tissue chip

2012, S2• Sabu Thomas,Yves Grohens,Neethu Ninan, Nanotechnology Applications for Tissue

Engineering, 1st Edition, William Andrew (Elsevier) (Google Books): http://bit.ly/1DPqoTZ• Washington University in St. Louis, 3-D printer creates transformative device for heart

treatment: https://news.wustl.edu/news/Pages/26554.aspx• Norbert Pallua, Christoph V. Suscheck, Tissue Engineering From Lab to Clinic, 2011, Springer• Cato T. Laurencin, Lakshmi S. Nair, Nanotechnology and Regenerative Engineering: The

Scaffold, Second Edition, CRC Press, 2014 • I. Y. Wong, Bhatia, S. N., and Toner, M., “Nanotechnology: emerging tools for biology and

medicine.”, Genes Dev, vol. 27, no. 22, pp. 2397-408, 2013.• Lizhi Xu and al. 3D multifunctional integumentary membranes for spatiotemporal cardiac

measurements and stimulation across the entire epicardium, Nature Communications, 2014• R. Langer, D. A. Tirrell, Designing materials for biology and medicine, Nature 428, 2004• S. Yang et al. The design of scaffolds for use in tissue engineering. Part I. Traditional factors.

Tissue Engineering, 7(6):679–689, 2001

References

S. Yang et al. The design of scaffolds for use in tissue engineering. Part II. Rapid prototyping techniques. Tissue Engineering, 8:1–11, 2002• Molly S. Shoichet, Polymer Scaffolds for Biomaterials Applications, Macromolecules, 2010• I. E. Araci, P. Brisk, Recent developments in microfluidic large scale integration, Current

Opinion in Biotechnology Volume 25, 2014• X-J J Li Y Zhou, Microfluidic Devices for Biomedical Applications, Woodhead Publishing Series in

Biomaterials: Number 61, 2013

References

Questions

The End

Thank you for your attention