Cartilage Tissue Engineering for Joint Repair
Principal Investigator: Deborah Ciombor, PhD
The demand for therapeutic interventions for the treatment of musculoskeletal damage, especially repair or replacement of damaged cartilage, has increased dramatically in recent years. Currently available cartilage repair techniques have limitations, including limited healing, high cost, breakdown of the tissue implant leading to loss of function, and limited availability of competent cellular components. Therapeutic intervention for the repair of cartilage, including cell-based engineered repair, requires an understanding of the regulatory effects of growth factors and the potential for synergies with physical forces. In development, competent cells are exposed to spatial and temporal gradients of growth factors and proliferate or differentiate in response, creating complex tissues and organs. Additionally, the developing tissues are exposed to a changing microenvironment, which includes varying oxygen tensions.
- Synovial cells can be induced to undergo chondrogenesis in response to a temporal gradient of one growth factor, TGFß.;
- That the controlled release of a sequence of growth factors in encapsulated polymer microspheres and/or scaffolds can recapitulate developmental sequences of growth factor expression and
- That osteoblasts derived from human bone removed at TKR respond to varying conditions of hypoxia by changing their profile of gene expression.
The approach taken in studies proposed here explores the use of controlled oxygen environments to determine the response of tissue engineered constructs to changes in their physical microenvironment. The studies proposed here will characterize the response of these chondroprogenitor cells to a number of relevant growth factors and will define their optimum concentrations in a system which will mimic the oxygen gradients of a normal joint. Ciombor will use this information to further examine the resulting engineered construct of cartilage in an in vivo model of joint repair.
- Aaron RK, Ciombor DM, Lysaght M, Mathiowitz E, Ehrlich M. Regenerative medicine for limb trauma. Med Health R I. 2007; 90(1): 6-9.
- Aaron, R.K., Dyke J., Ciombor DM, Tung G. Perfusion Abnormalities in Subchondral Bone Associated with Marrow Edema, Osteoarthritis, and Avascular Necrosis. Ann N Y Acad Sci. 2007 Nov; 1117:124-37.
- Bilgen B, Orsini E, Aaron RK, Ciombor DM. FBS suppresses TGF-ß1-induced chondrogenesis in synoviocyte pellet cultures while dexamethasone and dynamic stimuli are beneficial. J Tissue Eng Regen Med. 2007 Nov-Dec;1(6):436-42.
- Ciombor DM, Aaron RK. Electric, electromagnetic, and acoustic treatment for avascular necrosis of the femoral head. Tech in Orthopaedics. 2008 Mar; 23(1):11-17.
- Jaklenec A, Hinckfuss A, Bilgen B, Ciombor DM, Aaron RK, Mathiowitz E. Sequential release of bioactive IGF-I and TGF-ß1 from PLGA microsphere-based scaffolds. Biomaterials. 2008 Apr; 29(10):1518-25.
- Covey D, Aaron RK, Baechler M, Born C, Ciombor DM, Keeney J, Mack A, Mazurek M, Richardson M, Shin A, Thompson M. Regenerative and restorative techniques to treat severe limb trauma orthopaedic war injuries: New developments in treatments and research. AAOS Instr Course Lect. 2009; 58:117-129.
- Lee JH, Dyke J, Ballon D, Aaron RK, Ciombor DM, Rosenwasser M. Subchondral fluid dynamics in a model of osteoarthritis: Use of dynamic contrast-enhanced magnetic resonance imaging. Osteoarthritis Cartilage. 2009 Oct; 17(10):1350-5.
- Lee JH, Dyke J, Ballon D, Ciombor DM, Tung G, Aaron RK. Assessment of Bone Perfusion with Contrast-Enhanced Magnetic Resonance Imaging. Orthop Clin N Am. 2009; 40:249-257.
- Bilgen B, Ren Y, Pei M, Aaron RK, Ciombor DM. CD14-Negative isolation enhances chondrogenesis in synovial fibroblasts. Tissue Eng. 2009; 15: 3261-3270.
- Valdes MA, Thakur NA, Namdari S, Ciombor DM, Palumbo M. Recombinant bone morphogenic protein-2 in orthopaedic surgery: a review. Arch Orthop Trauma Surg. 2009 Dec; 129 (12):1651-7.
- Gerin-Lajoie, Martin. Ciombor, Deborah McK. Warren, William H. Aaron, Roy K. Using ambulatory virtual environments for the assessment of functional gait impairment: a proof-of-concept study. Gait & Posture. 31(4):533-6, 2010 Apr.
- Puckett, Sabrina D. Lee, Phin Peng. Ciombor, Deborah M. Aaron, Roy K. Webster, Thomas J. Nanotextured titanium surfaces for enhancing skin growth on transcutaneous osseointegrated devices. Acta Biomaterialia. 6(6):2352-62, 2010 Jun.
- Chen, Yupeng. Bilgen, Bahar. Pareta, Rajesh A. Myles, Andrew J. Fenniri, Hicham. Ciombor, Deborah McK. Aaron, Roy K. Webster, Thomas J. Self-assembled rosette nanotube/hydrogel composites for cartilage tissue engineering. Tissue Engineering - Part C: Methods. 16(6):1233-43, 2010 Dec