HST.535

Tissue Engineering and Organ Regeneration

3-0-9 units · Graduate

Principles and practice of tissue engineering (TE) and organ regeneration (OR). Topics include: cellular/molecular processes that induce fibrosis following traumatic injury, surgical excision, disease, and aging; targets for treatment for induced regeneration; and the tools that can be used to formulate the treatments. Presents the basic science of organ regeneration. Principles underlying engineering strategies for employing select implantable or injectable biomaterial scaffolds, exogenous cells or their organelles, and drugs or regulatory molecules, for the formation of tissue in vitro (TE) and regeneration of tissues/organs in vivo (OR). Describes the technologies for producing biomaterial scaffolds and for incorporating cells and regulatory molecules into workable devices. Examples of clinical successes and failures of regenerative devices are analyzed as case studies.

Fall 2024

This course presents the fundamentals of tissue engineering (TE) and organ regeneration (OR). Emphasis is on clinical translation and the development of workable medical devices. Topics include factors that prevent the spontaneous regeneration of tissues/organs in the adult (following traumatic injury, surgical excision, disease, and aging), and the cellular and molecular mechanisms that can identify the agents to employ therapeutically to enable induced regeneration. A principal focus is the assessment of the criteria that need to be met by biomaterials to deliver these agents and to fill defects. The course presents the principles underlying strategies for employing select biomaterial scaffolds, exogenous cells, and soluble regulators for the formation of tissue in vitro (TE) and regeneration of tissues/organs in vivo (regenerative medicine / OR). The course describes the methodologies for producing biomaterial scaffolds to accommodate the infiltration of endogenous cells (e.g., for the treatment of stroke) and for delivering cells and regulatory molecules (e.g., for the treatment of blindness). Examples of clinical successes and failures of regenerative devices are analyzed as case studies.

Fall 2004 · Principles and Practice of Tissue Engineering

The principles and practice of tissue engineering (and regenerative medicine) are taught by faculty of the Harvard-MIT Division of Health Sciences and Technology (HST) and Tsinghua University, Beijing, China. The principles underlying strategies for employing selected cells, biomaterial scaffolds, soluble regulators or their genes, and mechanical loading and culture conditions, for the regeneration of tissues and organs _in vitro_ and _in vivo_ are addressed. Differentiated cell types and stem cells are compared and contrasted for this application, as are natural and synthetic scaffolds. Methodology for the preparation of cells and scaffolds in practice is described. The rationale for employing selected growth factors is covered and the techniques for incorporating their genes into the scaffolds are examined. Discussion also addresses the influence of environmental factors including mechanical loading and culture conditions (e.g., static versus dynamic). Methods for fabricating tissue-engineered products and devices for implantation are taught. Examples of tissue engineering-based procedures currently employed clinically are analyzed as case studies. Archived webcast lecture videos for the Fall 2008 version of this class can be found at the {{% resource_link "85ea41c2-a11e-4be3-a310-3418ae5629d5" "HST.535 Fall 2008 website" %}}.

Readings

Readings for the subject will comprise lecture notes, Microsoft® PowerPoint® slides, journal articles, and selections from textbooks. This page lists the journal articles and textbook selections for each lecture session.
Listed reading
In lieu of a course text, this page also presents all of the readings organized in a “ virtual textbook .” ↗
Listed reading
Liu, Wei, Lei Cui, and Yilin Cao. “A Closer View of Tissue Engineering in China: The Experience of Tissue Construction in Immunocompetent Animals.” Tissue Engineering 9, Suppl. 1 (2003): S17-S30.
Listed reading
Xiang, Zhou, and Myron Spector. “A Glimpse of Tissue Engineering in China.” Tissue Engineering 8, no. 2 (2002): 169-174.
Listed reading
Spector, M. “Novel Cell–Scaffold Interactions Encountered in Tissue Engineering: Contractile Behavior of Musculoskeletal Connective Tissue Cells.” Tissue Engineering 8, no. 3 (2002): 351-357.
Listed reading
Chamberlain, Lila J., and Loannis V. Yannas. “Preparation of Collagen-Glycosaminoglycan Copolymers for Tissue Regeneration.” Tissue Engineering Methods and Protocols. Vol. 18, Methods in Molecular Medicine . Edited by J. R. Morgan and M. L. Yarmush. Totowa, NJ: Humana Press Inc., 1998, pp. 3-17. ISBN: 9780896035164 .
Listed reading
Ellis, D. L., and I. V. Yannas. “Recent Advances in Tissue Synthesis in Vivo by use of Collagen-Glycosaminoglycan Copolymers.” Biomaterials 17, no. 3 (1996): 291-299.
Listed reading
Yannas, Ioannis V. “Synthesis of Organs: In Vitro or in Vivo ?” PNAS 97, no. 17 (August 15, 2000): 9354-9356.
Listed reading
Wang, X. H., D. P. Li, W. J. Wang, Q. L. Feng, F. Z. Cui, Y. X. Xu, X. H. Song, and Mark van der Werf. “Crosslinked Collagen/Chitosan Matrix for Artificial Livers.” Biomaterials 24 (2003): 3213-3220.
Listed reading
Curodeau, Alan, Emanuel Sachs, and Salvatore Caldarise. “Design and Fabrication of Cast Orthopedic Implants with Freeform Surface Textures from 3-D Printed Ceramic Shell.” J. Biomed. Mater. Res. (Appl. Biomater.) 53 (2000): 525-535. (John Wiley & Sons, Inc.)
Listed reading
Yan, Yongnian, Zhuo Xiong, Yunyu Hu, Shenguo Wang, Renji Zhang, and Chao Zhang. “Layered Manufacturing of Tissue Engineering Scaffolds via Multi-Nozzle Deposition.” Materials Letters 57 (2003): 2623–2628.
Listed reading
Xiong, Zhuo, Yongnian Yan, Shenguo Wang, Renji Zhang, and Chao Zhang. “Fabrication of Porous Scaffolds for Bone Tissue Engineering via Low-temperature Deposition.” Scripta Materialia 46 (2002): 771–776.
Listed reading
Kisiday, J., M. Jin, B. Kurz, H. Hung, C. Semino, S. Zhang, and A. J. Grodzinsky. “Self-Assembling Peptide Hydrogel Fosters Chondrocyte Extracellular Matrix Production and Cell Division: Implications for Cartilage Tissue Repair.” PNAS 99, no. 15 (July 23, 2002): 9996–10001.
Listed reading
Zhang, Shuguang, Todd C. Holmes, C. Michael DiPersio, Richard O. Hynes, Xing Su, and Alexander Rich. “Self-Complementary Oligopeptide Matrices Support Mammalian Cell Attachment.” Biomaterials 16 (1995): 1385-1393.
Listed reading
Zhang, Shuguang, Davide M. Marini, Wonmuk Hwang, and Steve Santoso. “Design of Nanostructured Biological Materials through Self-Assembly of Peptides and Proteins.” Current Opinion in Chemical Biology 6 (2002): 865–871.
Listed reading
Kojima, Koji, Lawrence J. Bonassar, Amit K. Roy, Hirokazu Mizuno, Joaquin Cortiella, and Charles A. Vacanti. “A Composite Tissue-Engineered Trachea using Sheep Nasal Chondrocyte and Epithelial Cells.” Faseb J. 17 (2003): 823-828.
Listed reading
Vacanti, Martin P., Amit Roy, Joaquin Cortiella, Lawrence Bonassar, and Charles A. Vacanti. “Identification and Initial Characterization of Spore-Like Cells in Adult Mammals.” Journal of Cellular Biochemistry 80 (2001): 455-460.
Listed reading
Du, C., F. Z. Cui, W. Zhang, Q. L. Feng, X. D. Zhu, and K. de Groot. “Formation of Calcium Phosphate/Collagen Composites through Mineralization of Collagen Matrix.” J. Biomed. Mater. Res . 50 (2000): 518–527. (John Wiley & Sons, Inc.)
Listed reading
Zhang, W., S. S. Liao, and F. Z. Cui. “Hierarchical Self-Assembly of Nano-Fibrils in Mineralized Collagen.” Chem. Mater . 15 (2003): 3221-3226.
Listed reading
Buschmann, Michael D., Yehezkiel A. Gluzband, Alan J. Grodzinsky, and Ernst B. Hunziker. “Mechanical Compression Modulates Matrix Biosynthesis in Chondrocyte/Agarose Culture.” Journal of Cell Science 108 (1995): 1497-1508.
Listed reading
Grodzinsky, A. J., Y-J. Kim, and M. A. DiMicco. “Response of The Chondrocyte to Mechanical Stimuli.” Section 7.2.1.5 in Osteoarthritis. 2nd ed. Edited by Kenneth D. Brandt, Michael Doherty, and Stefan Lohmander. New York, NY: Oxford University Press, 2003. ISBN: 9780198509677 .
Listed reading
Martin, Ivan, R. Suetterlin, W. Baschong, M. Heberer, G. Vunjak-Novakovic, and L. E. Freed. “Enhanced Cartilage Tissue Engineering by Sequential Exposure of Chondrocytes to FGF-2 During 2D Expansion and BMP-2 During 3D Cultivation.” Journal of Cellular Biochemistry 83 (2001): 121-128.
Listed reading
Samuel, R. E., C. R. Lee, S. C. Ghivizzani, C. H. Evans, I. V. Yannas, B. R. Olsen, and M. Spector. “Delivery of Plasmid DNA to Articular Chondrocytes via Novel Collagen–Glycosaminoglycan Matrices.” Human Gene Therapy 13 (May 1, 2002): 791–802.
Listed reading
Lieberman, Jay R., Steven C. Ghivizzani, and Christopher H. Evans. “Gene Transfer Approaches to the Healing of Bone and Cartilage.” Molecular Therapy 6, no. 2, (August 2002): 141-147.
Listed reading
Yannas, I. V., J. F. Burke, D. P. Orgill, and E. M. Skrabut. “Wound Tissue can Utilize a Polymeric Template to Synthesize a Functional Extension of Skin.” Science 215, no. 4529 (January 8, 1982): 174-176. (New Series)
Listed reading
Yannas, I. V., E. Lee, D. P. Orgill, E. M. Skrabut, and G. F. Murphy. “Synthesis and Characterization of a Model Extracellular Matrix that Induces Partial Regeneration of Adult Mammalian Skin.” Proceedings of the National Academy of Sciences of the United States of America 86, no. 3 (February 1, 1989): 933-937.
Listed reading
Yang, Fei, Xunhu Li, Mingyu Cheng, Yandao Gong, Nanming Zhao, Xiufang Zhang, and Yinye Yang. “Performance Modification of Chitosan Membranes Induced by Gamma Irradiation.” Journal of Biomaterials Applications 00 (November 2001): 1-12.
Listed reading
Haipeng, Gong, Zhong Yinghui, Li Jianchun, Gong Yandao, Zhao Nanming, and Zhang Xiufang. “Studies on Nerve Cell Affinity of Chitosan-Derived Materials.” J. Biomed. Mater. Res . 52 (2000): 285–295. (John Wiley & Sons, Inc.)
Listed reading
Cheng, Mingyu, Jinguang Deng, Fei Yang, Yandao Gong, Nanming Zhao, and Xiufang Zhang. “Study on Physical Properties and Nerve Cell Affinity of Composite Films from Chitosan and Gelatin Solutions.” Biomaterials 24 (2003): 2871–2880.
Listed reading
Mitchell, Shannon L., and Laura E. Niklason. “Requirements for Growing Tissue-Engineered Vascular Grafts.” Cardiovascular Pathology 12 (2003): 59-64.
Listed reading
Niklason, L. E., J. Gao, W. M. Abbott, K. K. Hirschi, S. Houser, R. Marini, and R. Langer. “Functional Arteries Grown in Vitro .” Science 284 (April 16, 1999): 489-493.
Listed reading
Rabkin, Elena, and Frederick J. Schoen. “Cardiovascular Tissue Engineering.” Cardiovascular Pathology 11 (2002): 305-317.
Listed reading
Schoen, Frederick J., and Robert J. Levy. “Tissue Heart Valves: Current Challenges and Future Research Perspectives.” J. Biomed. Mater. Res . 47 (1999): 439–465. (John Wiley & Sons, Inc.)
Listed reading
De Filippo, Roger E., James J. Yoo, and Anthony Atala. “Urethral Replacement using Cell Seeded Tubularized Collagen Matrices.” The Journal of Urology 168 (October 2002): 1789–1793.
Listed reading
———. “Engineering of Vaginal Tissue in Vivo .” Tissue Engineering 9, no. 2 (2003): 301-306.
Listed reading
Liu, Yanchun, Fuguo Chen, Wei Liu, Lei Cui, Qingxin Shang, Wangyao Xia, Jian Wang, Yimin Cui, Guanghui Yang, Deli Liu, Juanjuan Wu, Rong Xu, Samuel D. Buonocore, and Yilin Cao. “Repairing Large Porcine Full-Thickness Defects of Articular Cartilage Using Autologous Chondrocyte-Engineered Cartilage.” Tissue Engineering 8, no. 4 (2002): 709-721.
Listed reading
Mao, Jinshu, Liguo Zhao, Kang de Yao, Qingxin Shang, Guanghui Yang, and Yilin Cao. “Study of Novel Chitosan-gelatin Artificial Skin in Vitro .” J. Biomed. Mater. Res. 64A (2003): 301–308. (Wiley Periodicals, Inc.)
Listed reading
Liao, S. S., K. Guan, F. Z. Cui, S. S. Shi, and T. S. Sun. “Lumbar Spinal Fusion with a Mineralized Collagen Matrix and rhBMP-2 in a Rabbit Model.” SPINE 28, no. 17 (2003).
Listed reading
Wanga, Xiaohong, Jianbiao Ma, Qingling Feng, and Fuzhai Cui. “Skeletal Repair in Rabbits with Calcium Phosphate Cements Incorporated Phosphorylated Chitin.” Biomaterials 23 (2002): 4591–4600.
Listed reading
Yu X., L. Xu, X. D. Zhang, and F. Z. Cui. “Effect of Spinal Cord Injury on Urinary Bladder Spinal Neural Pathway: A Retrograde Transneuronal Tracing Study with Pseudorabies Virus.” Urology 62, no. 4 (2003): 1-5.
Listed reading
Lee, C. R., A. J. Grodzinsky, H. -P. Hsu, and M. Spector. “Effects of a Cultured Autologous Chondrocyte-Seeded Type II Collagen Scaffold on the Healing of a Chondral Defect in a Canine Model.” Journal of Orthopaedic Research 21 (2003): 272–281.
Listed reading
Melkerson, M. N. “ Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Regulated as Devices .” US FDA Tissue Reference Group (TRG), August 29, 2001. ↗
Listed reading
CHAPTER #: Section 0: Introduction to Tissue Engineering in China
Reading assignment
CHAPTER #: S0. Introduction to Tissue Engineering in China
Reading assignment
CHAPTER #: Section 1: Scaffolds
Reading assignment
CHAPTER #: S1 A. Overview · READINGS: Spector, M. “Novel Cell–Scaffold Interactions Encountered in Tissue Engineering: Contractile Behavior of Musculoskeletal Connective Tissue Cells.” Tissue Engineering 8, no. 3 (2002): 351-357.
Reading assignment
CHAPTER #: S1 B. Historical Perspective and Design Criteria · READINGS: See notes for LEC 1.
Reading assignment
CHAPTER #: S1 C. Collagen-GAG Analogs of Extracellular Matrix
Reading assignment
CHAPTER #: S1 D. Free-Form Manufacturing
Reading assignment
Curodeau, Alan, Emanuel Sachs, and Salvatore Caldarise. “Design and Fabrication of Cast Orthopedic Implants with Freeform Surface Textures from 3-D Printed Ceramic Shell.” J. Biomed. Mater. Res. (Appl. Biomater.) 53 (2000): 525–535. (John Wiley & Sons, Inc.)
Listed reading
CHAPTER #: S1 E. Self-Assembled Proteins
Reading assignment
Kisiday, J., M. Jin, B. Kurz, H. Hung, C. Semino, S. Zhang, and A. J. Grodzinsky. “Self-Assembling Peptide Hydrogel Fosters Chondrocyte Extracellular Matrix Production and Cell Division: Implications for Cartilage Tissue Repair.” PNAS 99, no. 15 (23 July 2002): 9996–10001.
Listed reading
CHAPTER #: S1 F. Biomimetics Design
Reading assignment
CHAPTER #: Section 2: Cells
Reading assignment
CHAPTER #: S2 A. Sources
Reading assignment
CHAPTER #: S2 B. Differentiated versus Stem Cell · READINGS: See notes for LEC 4: ( PDF ) ↗
Reading assignment
CHAPTER #: S2 C. Liver Cells · READINGS: Wang, X. H., D. P. Li, W. J. Wang, Q. L. Feng, F. Z. Cui, Y. X. Xu, X. H. Song, and Mark van der Werf. “Crosslinked Collagen/Chitosan Matrix for Artificial Livers.” Biomaterials 24 (2003): 3213-3220.
Reading assignment
CHAPTER #: S2 D. Effects of Culture Conditions · READINGS: See notes for LEC 5: ( PDF ) (Courtesy of Dr. Lisa Freed. Used with permission.) ↗
Reading assignment
CHAPTER #: S2 E. Embryonic and Other Stem Cells · READINGS: No materials; discussed by Prof. Guo in LEC 8.
Reading assignment
CHAPTER #: Section 3: Regulators
Reading assignment
CHAPTER #: S3 A. Response to Mechanical Loading
Reading assignment
Grodzinsky, A. J., Y-J. Kim, and M. A. DiMicco. “Response of the chondrocyte to mechanical stimuli.” Section 7.2.1.5 in Osteoarthritis. 2nd ed. Edited by Kenneth D. Brandt, Michael Doherty, and Stefan Lohmander. New York: Oxford University Press, 2003. ISBN: 9780198509677 .
Listed reading
CHAPTER #: S3 B. Roles of Environmental Factors · READINGS: Martin, Ivan, R. Suetterlin, W. Baschong, M. Heberer, G. Vunjak-Novakovic, and L. E. Freed. “Enhanced Cartilage Tissue Engineering by Sequential Exposure of Chondrocytes to FGF-2 During 2D Expansion and BMP-2 During 3D Cultivation.” Journal of Cellular Biochemistry 83 (2001): 121-128.
Reading assignment
CHAPTER #: S3 C. Principles of Gene Therapy · READINGS: No materials; discussed by Dr. Chang in LEC 8.
Reading assignment
CHAPTER #: S3 D. Gene Transfer Wedded to Tissue Engineering
Reading assignment
CHAPTER #: Section 4: Applications
Reading assignment
CHAPTER #: S4 A. Skin and Peripheral Nerve
Reading assignment
CHAPTER #: S4 B. Nerve Repair
Reading assignment
Haipeng, Gong, Zhong Yinghui, Li Jianchun, Gong Yandao, Zhao Nanming, and Zhang Xiufang. “Studies on Nerve Cell Affinity of Chitosan-Derived Materials.” J Biomed Mater Res . 52 (2000): 285–295. (John Wiley & Sons, Inc.)
Listed reading
CHAPTER #: S4 C. Blood Vessels
Reading assignment
Niklason, L. E., J. Gao, W. M. Abbott, K. K. Hirschi, S. Houser, R. Marini, and R. Langer. “Functional Arteries Grown in Vitro.” Science 284 (16 April 1999): 489-493.
Listed reading
CHAPTER #: S4 D. Heart Valves
Reading assignment
Schoen, Frederick J., and Robert J. Levy. “Tissue Heart Valves: Current Challenges and Future Research Perspectives.” J Biomed Mater Res . 47 (1999): 439–465. (John Wiley & Sons, Inc.)
Listed reading
CHAPTER #: S4 E. Urinary Tissues/Organs
Reading assignment
CHAPTER #: S4 F. Clinical Applications and Underlying Principles
Reading assignment
Mao, Jinshu, Liguo Zhao, Kang de Yao, Qingxin Shang, Guanghui Yang, and Yilin Cao. “Study of Novel Chitosan-gelatin Artificial Skin in Vitro.” J Biomed Mater Res. 64A (2003): 301–308. (Wiley Periodicals, Inc.)
Listed reading
CHAPTER #: S4 G. Bone Regeneration
Reading assignment
Liao, S. S., K. Guan, F. Z. Cui, S. S. Shi, and T. S. Sun. “Lumbar Spinal Fusion With a Mineralized Collagen Matrix and rhBMP-2 in a Rabbit Model.” Spine 28, no. 17 (2003): 1-7.
Listed reading
CHAPTER #: S4 H. Cartilage Repair · READINGS: Lee, C. R., A. J. Grodzinsky, H. -P. Hsu, and M. Spector. “Effects of a Cultured Autologous Chondrocyte-Seeded Type II Collagen Scaffold on the Healing of a Chondral Defect in a Canine Model.” Journal of Orthopaedic Research 21 (2003): 272–281.
Reading assignment
CHAPTER #: S4 I. Federal Regulatory Issues for Tissue Engineering Products in the U.S., China, and other Countries · READINGS: Melkerson, M. N. “ Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Regulated as Devices .” US FDA Tissue Reference Group (TRG), August 29, 2001. ↗
Reading assignment
CHAPTER #: S4 J. Brain Repair · READINGS: No materials.
Reading assignment
CHAPTER #: S4 K. Spinal Cord, Lung, and Heart · READINGS: No materials; discussed by Prof. Cui in LEC 13.
Reading assignment

Prerequisites & course information

Same subject as 2.787[J] Prereq: ( Biology (GIR) , Chemistry (GIR) , and Physics I (GIR) ) or permission of instructor G (Fall) 3-0-9 units

Sources

Course catalogue ↗2026–2027
MIT OpenCourseWare ↗Fall 2024
MIT OCW calendar ↗
MIT OCW syllabus ↗
MIT OpenCourseWare ↗Fall 2004
MIT OCW syllabus ↗
MIT OCW readings ↗
MIT OCW calendar ↗
Historical MIT OpenCourseWare offering. Named reading entries and schedule topics are automatically extracted from the linked source pages.
Historical MIT OpenCourseWare offering. Named reading entries and schedule topics are automatically extracted from the linked source pages.