Regenerative Biosciences and Engineering

Transcription

1 Regenerative Biosciences and Engineering Research at Gateway Park George D. Pins, Ph.D. Department of Biomedical Engineering Worcester Polytechnic Institute, Worcester, MA WPI Impact November 18, 2008 What is Regenerative Biosciences and Engineering (Tissue Engineering)? The application of the principles and methods of engineering and life sciences toward the development of biological substitutes to restore, maintain or regenerate damaged tissues/organs. 1

2 Indication Clinical Need Procedures/year Skin 2,750,000 Blood vessels 1,360, Bone 1,343,000 Cartilage/tendon/ligament 1,253,000 Pancreas 728,000 Kidney 600,000 Breast 261,000 Liver 205,000 Neuromuscular 200,000 Intestine 100,000-65,000 people awaiting transplants Objective of Regenerative Biosciences and Engineering Design replacements to regenerate damaged tissues and organs Biomaterials Cells Composites How do 3-D cellular microenvironments modulate cell and tissue function? (an integrated solution) 2

3 Building Collaborations at Gateway Park Dept. Biology / Biotechnology Stem cells/developmental biology Regenerative medicine Dept. Biomedical Engineering Dept. Chemistry Surface design / characterization Dept. Chem. Eng. Bioreactor design Bioengineering Institute Biotech. Start-up (eg. RXi, Inc.) Univ. Mass. Med. School (UMMS) Surgery Cancer Biology Molecular Medicine RNAi Center for Regenerative Bioscience & Engineering Center (CRBE) at WPI 12 Faculty Members from 4 Academic Departments Cell/Tissue Therapy: Engineered Skin Grafts (Burns) Engineered Blood Vessels (Vascular Surgery) Traumatic Tissue Loss (Muscle Injury) Heart Disease (myocardial infarction) Wound Infection Non-Embryonic Stem Cell Platform Technologies Cell Delivery Technology Cell De-Differentiation Technology Bioreactors for Tissue Construction 3

4 Regenerative Cell Technologies Induced pluripotency Cell signaling Infection/inflammation CRBE: Strategic Plan Engineering Technologies Translation technologies Development of animal models Commercialization Applications Bioengineered skin substitutes Cardiac regeneration Tissue engineered vascular grafts Cell transplantation Delivery systems Scaffold engineering Biomechanics Functional tissue assessment Product Development Industry Therapy Clinics/Patients Commercially available skin substitutes: Integra Apligraft Limitations still exist! Need for secondary procedure Inconsistent graft take Prolonged wound healing times Mechanically induced graft failure Clinical Need: Bioengineered Skin Substitutes Integra A need still remains for an off-the-shelf skin substitute that provides a robust replacement of both the dermis and epidermis. [1] [1] Morgan and Yarmush,

5 Approach Microtextured Basal Lamina Analogs and Cultured Skin Equivalents Skin Equivalents with Microfabricated Basal Lamina Analogs Human keratinocytes cultured at air-liquid interface (7 days) ET ET (Downing, JBMR, 72A: 47) 5

6 Kristen Billiar, Ph.D. B.S., Cornell University, Mechanical Engineering Ph.D., University of Pennsylvania, Bioengineering Industry, Organogenesis, Inc., Tissue Engineering Company Research Interests (Tissue Mechanics and Mechanobiology): The mechanics of dermal healing The mechanical environment (stretch, stiffness) effects the healing of wounds Seen clinically with range of motion exercises and splinting We engineer tissues in the lab and study these effects Heart valve mechanobiology and tissue engineering Heart valves are loaded by blood pressure every heart beat Cells become activated by damage or excessive loading We are finding that excessive activation may lead to pathology Bone fixation and repair Following heart surgery the sternum must be put back together Rigid fixation offers advantages over wires in some patients We are studying the mechanics of bone fixation Tissue Mechanics and Mechanobiology (Prof. Kris Billiar) Worcester Polytechnic Institute 12 6

7 Customizing Regenerative Medicine Without Stem Cells Re-growing lost tissues The same cells direct healing events after amputation in amphibians and humans, but with a very different outcome Connective tissue fibroblasts - ipcs Drs. Ray Page and Tanja Dominko EUREKA!!!!! Healing Burns With Engineered Skin Skin cells grown on engineered biomaterials 7

8 Coronary heart disease can lead to ischemia Affects ~ 16 million Americans Heart attack (myocardial infarction) results in muscle tissue death Affects ~ 8 million Americans Heart does not repair itself Results in scar Scar tissue cannot contract Heart Disease 1 1. American Heart Association. HeartDisease andstroke Statistics Can We Regenerate Myocardium in the 21 st Century? Cell Therapy Approaches 1. Endogenous repair increase myocyte mass with native cells a. Myocyte proliferation b. Progenitor cell recruitment/differentation 2. Exogenous repair delivering cells that become cardiac myocytes a. Embryonic stem cells b. hmscs Differentiation in vivo c. hmscs- Differentiation in vitro d. Cardiac stem cells e. Cardiogenic cells Require Delivery Vehicle 8

9 Prof. Glenn Gaudette Research Interest Cardiac Regeneration Induction of native cardiac myocyte proliferation Turning adult stem cells into cardiac myocytes y Using biological scaffolds to replace infarcted heart tissue Worcester Polytechnic Institute 17 Extracellular Matrix Assembly and Tissue Engineering Prof Marsha Rolle 100 µm 50 µm Gene- and cell-based approaches to control ECM synthesis and organization for tissue engineering Worcester Polytechnic Institute 18 K Helmer,

10 Biological Microthreads for Delivering Stem Cells to the Heart Designing Collagen and Fibrin Microthreads Tendon/Ligament Repair: 250,000 injuries/year, $5 billion/year 1 Cornwell, JBMR, 2004/

11 hmsc Delivery to the Heart Needle Microthreads Loading Cells on Microthreads 3.0 cm Stainless Steel Washer Silastic Microthread Bundle Thermanox TM 100 ul cell suspension Sterilized in 70% isopropyl alcohol Statically seeded 50,000 hmscs passage 4 to 9 in 100uL of media Figure adapted from J. Guyette 11

12 Conclusion Microthreads support a physiologically relevant number of hmscs hmscs remain viable hmscs can proliferate on microthreads hmscs retain multipotency after culture on microthreads Microthread Bundles in the Heart 12

13 Regenerative Cell Technologies Induced pluripotency Cell signaling Infection/inflammation CRBE: What s next??? Engineering Technologies Translation technologies Development of animal models Commercialization Applications Bioengineered skin substitutes Cardiac regeneration Tissue engineered vascular grafts Cell transplantation Delivery systems Scaffold engineering Biomechanics Functional tissue assessment Product Development Industry Therapy Clinics/Patients Collaborators: Stelios Andreadis, SUNY-Buffalo Pedro Lei, SUNY-Buffalo Kris Billiar, WPI Tanja Dominko, WPI Ray Page, WPI Glenn Gaudette, WPI Marsha Rolle, WPI Dept. Ob/Gyn - UMMS Graduate Students: Kevin Cornwell Katie Bush Brett Downing Stuart Howes Jen Makridakis Tracy Gwyther Jacques Guyette Megan Murphy Acknowledgements (Pins Lab) Undergrad Students: Shawn Carey Deepti Kalluri Sahit Bhagat Jason Robinson Gharam Han Donna Davidson Christina Mezzone REU Students: Kirsten Kinneberg Erica Levorson Thread MQP Team: William Bishop Diana Camire Ngoc Chau Duong Jason Robinson Funding: NIH, TATRC, Whitaker Foundation Faculty Advancement in Research (WPI) 13

14 Building Collaborations at Gateway Park Center for Regenerative Biosciences and Engineering AHA, Corporate Biomedical Engineering Kristen Billiar, PhD Glenn Gaudette,, PhD George Pins, PhD Marsha Rolle, PhD Biology and Biotechnology Tanja Dominko, DVM, PhD Joe Duffy, PhD Eric Overstrom, PhD Raymond Page, PhD Reeta Prusty Rao, PhD Chemistry and Biochemistry Christopher Lambert, PhD Grant McGimpsey, PhD Chemical Engineering Terri Camesano, PhD Additional Information Center for Regenerative Biosciences and Engineering (CRBE) CRBE Website Centers/regenerative.html Research at WPI Life Sciences Initiatives at WPI Gateway Park Website y 14