Intrinsic repair of articular cartilage damage is unsatisfactory, largely due to its avascular natue and demanding physical environment. Hydrogels are attractive biomaterials for cartilage regeneration, as they can conform within complex chondral defects, adhere to and integrate with surrounding tissues, and encapsulate and direct stem cell differentiation.
The aim of this study is to evaluate a novel hyaluronic acid hydrogel seeded with mesenchymal stem cells in a cartilage defect in a large animal model. We will specifically address two different approaches for cartilage restoration using this system: 1) direct fabrication of the engineered material in th cartilage defect, where differentiation and maturation is controlled by co-encapsulated growth factor- laden microspheres, and 2) implantation of an engineered construct that has been pre- matured ex vivo under defined conditions to attain cartilage-relevant mechanical and biochemical properties. Optimization of each approach will involve detailed analysis of cartilage properties after implantation using advanced mechanical and imaging modalities. If successful, this work has the potential to dramatically change the course of treatment of persons with significant cartilage injuries and osteoarthritic degeneration, and as such, would improve the lives of military personnel and society as a whole.

Public Health Relevance

Intrinsic repair of articular cartilage damage is unsatisfactory, due to its avascular nature and demanding physical environment. Military personnel suffer from cartilage damage at a higher rate than the general population, restricting active duty and leading to the development of osteoarthritis (OA) and the need for total joint replacement. The aim of this study is to evaluate novel tissue engineered construct based on a hyaluronic acid hydrogel seeded with mesenchymal stem cells. We will determine the best route towards clinical efficacy, i.e., direct formation of the engineered material within the defect, or a process where tissues are matured in vitro and then implanted. This work will dramatically improve treatment options for the military population suffering from acute cartilage injury and those debilitated from the ravages of progressive OA.

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
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Translational Rehab (Basic) (RRD0)
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Philadelphia VA Medical Center
United States
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Kim, Minwook; Farrell, Megan J; Steinberg, David R et al. (2017) Enhanced nutrient transport improves the depth-dependent properties of tri-layered engineered cartilage constructs with zonal co-culture of chondrocytes and MSCs. Acta Biomater 58:1-11
Vega, Sebastián L; Kwon, Michelle; Mauck, Robert L et al. (2016) Single Cell Imaging to Probe Mesenchymal Stem Cell N-Cadherin Mediated Signaling within Hydrogels. Ann Biomed Eng 44:1921-30
Fisher, Matthew B; Belkin, Nicole S; Milby, Andrew H et al. (2016) Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair in a Mini-Pig Model. Cartilage 7:174-84
Pfeifer, Christian G; Fisher, Matthew B; Carey, James L et al. (2015) Impact of guidance documents on translational large animal studies of cartilage repair. Sci Transl Med 7:310re9
Mauck, Robert L; Burdick, Jason A (2015) From repair to regeneration: biomaterials to reprogram the meniscus wound microenvironment. Ann Biomed Eng 43:529-42
Fisher, Matthew B; Henning, Elizabeth A; Söegaard, Nicole B et al. (2014) Maximizing cartilage formation and integration via a trajectory-based tissue engineering approach. Biomaterials 35:2140-8