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Laboratory for Musculoskeletal Tissue Engineering

The mission of the Laboratory for Musculoskeletal Tissue Engineering is to conduct cutting edge research in tissue engineering and regenerative medicine for repairing and regenerating musculoskeletal tissues. Programs have been developed in three primary areas: 1) articular cartilage repair and regeneration; 2) meniscal repair and replacement; and 3) photochemical tissue bonding to promote healing.

The Laboratory for Musculoskeletal Tissue Engineering, under the direction of Mark Randolph, is devoted to regenerative approaches for musculoskeletal repair. Together they have a research program exploring tissue engineering approaches to repair and regenerate cartilage and other soft connective tissues. Their primary interest focuses on repair and regeneration of traumatic sports-related injuries, particularly to the shoulder and knee.

One area of investigation is developing novel photocurable hydrogel polymers for delivering chondrocytes or chondrogenic precursor cells to cartilage defects. Using this approach, cells can be incorporated into the liquid phase of the polymers, injected into a defect area, and the gel polymerized in situ. The expected outcome is that new cartilage matrix is formed as the polymer biodegrades. In vivo results have been published using fibrin polymer, poly (ethylene glycol), and hyaluronic acid gels. Ongoing work sponsored by the US Department of Defense in collaboration with Dr. Kristi Anseth, a chemical engineer at the University of Colorado, is exporing other novel photochemically crosslinked gels such as collagen and norbornene gels. With greater understanding of cell polymer interactions, and the possible incorporation of growth factors, it may be possible to engineer cartilage that resembles native cartilage in every parameter.

Another area of active investigation is studying the integration of cell-seeded scaffolds and engineered cartilage with the native cartilage surrounding the defect. The poor healing capacity of injured cartilage is well established. To augment healing, it may be possible to use cell-seeded scaffolds to deliver chondrocytes or chondrogenic precursor cells to induce matrix formation and healing. Along with Dr. Lawrence Bonassar from Cornell University, we have published several reports on the potential for chondrocytes to bond or heal cartilage discs together with measurable forces. To extend this into a preclinical model, cell-seeded scaffolds have been inserted into bucket-handle lesions in swine with some success. Recent work has examined an approach using allogeneic cells and new scaffold material to repair lesions in swine knees.

The Sports Medicine Service has joined with the Center for Regenerative Medicine in a collaborative program to develop the use of stem cells in the regeneration of cartilage and to explore the tissue interactions among bone,cartilage, tendons and ligaments. The overall objective of these studies is to understand better the biology of the musculoskeletal system and to develop new theraputic approaches to treating orthopaedic diseases.

Faculty

  • Mark A. Randolph, MS
  • Xing Zhao, MD

Former Postdoctoral Fellows

  • David Bichara, MD (Research fellow, 2007- 2010)
  • Anestis Papadopoulis, MD (Research fellow, 2004-2006)
  • Shinichi Ibusuki, MD, PhD (Research fellow, 2003-2005)
  • Jeong Joon Yoo, MD, PhD (Research fellow, 2008-2010)

Research Technician

  • Mark A. Omobono, BS (Research Technologist 2010- )

Students

  • William Johnson, BS (HMS medical student 2011)
  • Winnie Ong, MS (BU master’s candidate 2010-2011)
  • Richard Erali, BS, (BU master’s candidate 2012-2013)

  • Photochemically Crosslinked Hydrogels for Articular Surface Repair and Regeneration
  • Meniscal Repair and Regeneration
  • Cartilage Ablation with Radiofrequency
  • Photochemical Tissue Bonding
  • The Musculoskeletal Regeneration Consortium was established recently as a joint program among the Center for Regenerative Medicine (David Scadden), the Endocrine Unit (Henry Kronenberg), the Tissue Engineering Laboratory (Mark Randolph), and the Sports Medicine Service (Thomas J. Gill IV). When new, clinically applicable discoveries are made, their effects will be examined first on cadaver studies in the Bioengineering Laboratory (Guoan Li) before proceeding to clinical trials. Other potential collaborators are available at Harvard College and at MIT. Dr. Thomas J. Gill III is involved in coordinating the various aspects of the program.

The laboratory provides training in research methodology to undergraduates, medical students, and postodoctoral research fellows.

  1. Zhao X, Bichara DA, Ballyns FP, Yoo JJ, Ong W, Randolph MA, Bonassar LJ, Gill T. Properties of Cartilage Engineered from Elderly Human Chondrocytes for Articular Surface Repair. Tissue Eng Part A. 2012 Jul;18(13-14):1490-9. Epub 2012 Jun 5. PubMed PMID: 22435677.
  2. Yoo JJ, Bichara DA, Zhao X, Randolph MA, Gill TJ. Implant-assisted meniscal repair in vivo using a chondrocyte-seeded flexible PLGA scaffold. J Biomed Mater Res A. 2011 Oct;99(1):102-8. doi: 10.1002/jbm.a.33168. Epub 2011 Jul 28. PubMed PMID: 21800420.
  3. Bichara DA, Zhao X, Bodugoz-Senturk H, Ballyns FP, Oral E, Randolph MA, Bonassar LJ, Gill TJ, Muratoglu OK. Porous poly(vinyl alcohol)-hydrogel matrix-engineered biosynthetic cartilage. Tissue Eng Part A. 2011 Feb;17(3-4):301-9. Epub 2010 Oct 12. PubMed PMID: 20799889.
  4. Ibusuki S, Papadopoulos A, Ranka MP, Halbesma GJ, Randolph MA, Redmond RW, Kochevar IE, Gill TJ. Engineering cartilage in a photochemically crosslinked collagen gel. J Knee Surg. 2009 Jan;22(1):72-81. PubMed PMID: 19216355.
  5. Ibusuki S, Halbesma GJ, Randolph MA, Redmond RW, Kochevar IE, Gill TJ. Photochemically cross-linked collagen gels as three-dimensional scaffolds for tissue engineering. Tissue Eng. 2007 Aug;13(8):1995-2001. PubMed PMID: 17518705.
  6. Chung C, Mesa J, Miller GJ, Randolph MA, Gill TJ, Burdick JA. Effects of auricular chondrocyte expansion on neocartilage formation in photocrosslinked hyaluronic acid networks. Tissue Eng. 2006 Sep;12(9):2665-73. PubMed PMID: 6995800; PubMed Central PMCID: PMC2678567.
  7. Weinand C, Peretti GM, Adams SB Jr, Bonassar LJ, Randolph MA, Gill TJ. An allogenic cell-based implant for meniscal lesions. Am J Sports Med. 2006 Nov;34(11):1779-89. Epub 2006 Jul 26. PubMed PMID: 16870819.
  8. Weinand C, Peretti GM, Adams SB Jr, Randolph MA, Savvidis E, Gill TJ. Healing potential of transplanted allogeneic chondrocytes of three different sources in lesions of the avascular zone of the meniscus: a pilot study. Arch Orthop Trauma Surg. 2006 Nov;126(9):599-605. Epub 2006 Jan 13. PubMed PMID: 16411123.
  9. Peretti GM, Gill TJ, Xu JW, Randolph MA, Morse KR, Zaleske DJ. Cell-based therapy for meniscal repair: a large animal study. Am J Sports Med. 2004 Jan-Feb;32(1):146-58. PubMed PMID: 14754738.

Mark Randolph

Laboratory Musculoskeletal Tissue Engineering
55 Fruit Street, WAC 435
Boston, MA 02114

Phone: 617-726-6943
Fax: 617-726-8998