Dynamic Self-regenerating Cartilage Construct For Cartilage Repair In The Hand
Yingfang Fan, MD, PhD1, Samuel D. Zarfos, BS1, Gem Runyan, MS1, Jongkil Kim, MS2, Stephen Sloan, MS2, Bonassar Lawrence, PhD2, Mark A. Randolph, MAS1, Robert W. Redmond, PhD1.
1Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA, 2Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
PURPOSE: Cartilage is avascular with limited capacity for repair and self-regeneration. Articular cartilage lesions in large joints have been successfully treated with autologous chondrocyte implantation (ACI) with or without a matrix scaffold (e.g., MACI). However, lesions in small joints of the hand and wrist cannot be easily treated with current ACI techniques. dynamic Self-Regenerating Cartilage (dSRC) has been shown successfully engineers contiguous articular cartilage matrix. The purpose of this study was to develop a new strategy that generating new cartilage matrix using dSRC to treat cartilage lesions in the joints of the hand and wrist.
METHODS: To form the dSRC, 107 freshly harvested autologous swine chondrocytes were placed into a 15-cc polypropylene tube and cultured on a rocker at 40 cycles per minute for 14 days at 37°C. During this time the chondrocytes aggregate and begin to make hyaline cartilage, forming a pellet of dSRC. To evaluate the cartilage formation of dSRC, additional culture was performed for 2, 4, 8, 10, and 12 weeks. Media changes were performed every 3-4 days. All constructs were evaluated histologically and immunohistochemically for cartilage formation, and biomechanical analysis.
RESULTS: Photograph showed the dSRC was injectable on week 2 and became thicker and more solid after 2 month and 3 months (Figure 1). After 8 weeks in vitro, dSRC generated contiguous new cartilage matrix, the cell number of week 8 dSRC was significantly decreased, compared to week 2 dSRC that showed hypercellular formation (Figure 2). All dSRC groups demonstrated intense staining with Safranin-O and Toluidine blue stains indicating high glycosaminoglycan (GAG) production (Figure 3). Immunohistochemical staining further confirmed that the matrix of dSRC was typical of normal hyaline cartilage, rich in collagen type II and no collagen type I, similar to native cartilage (Figure 4). Aggregate modulus of the 3 month dSRC was ~20% of native cartilage. Results of this study demonstrate that dSRC itself can successfully engineer contiguous articular cartilage matrix in in vitro environments.
CONCLUSION: dSRC demonstrates successful hyaline cartilage formation in all different time points. Such a strategy could be employed to inject or implant dSRC in the smaller joints of hand and wrist to treat cartilage defects or osteoarthritis.
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