OPTIMIZING MMP7 DEGRADABLE HYDROGELS FOR CARTILAGE TISSUE ENGINEERING

Osteoarthritis is the most common chronic condition of the joints in which cartilage breaks down due to injury, overuse or bone misalignment. It debilitates patients because of the pain, inflammation, and swelling around the affected area. Advanced therapies involve cartilage tissue engineering in which cartilage tissue is derived from the patient and is used to replace the damaged cartilage. However, this approach is oftentimes unsuccessful due to aging and patient-to-patient variability. Photopolymerizable poly(ethylene glycol) hydrogels are used to address this challenge because they can recapitulate the complex microenvironment of cartilage tissue and can also be tuned to degrade at the rate needed by the patient’s cells. These hydrogels provide a solid foundation for human mesenchymal stem cells (hMSCs) to grow and deposit their own extracellular matrix as they differentiate into chondrocytes. However, it is imperative that the hydrogel is tuned to degrade at a rate that matches matrix deposition of the cells to allow space for the cells to integrate into cartilage tissue. This research proposes an enzymatically degradable hydrogel consisting of a degradable peptide crosslinker specific to matrix metalloproteinase (MMP7) which is associated with chondrogenic differentiation and cartilage remodeling. This allows for the gradual degradation of the hydrogel as the hMSCs differentiate into chondrocytes and should allow the cells the support and time needed for matrix deposition and tissue integration. Results demonstrate that MMP7 hydrogels degrade too quickly. Therefore an additional peptide crosslinker that degrades late in chondrogenesis will be added in future studies to fine-tune the degradation process.