Age impacts extracellular matrix metabolism in chondrocytes encapsulated in degradable hydrogels

Abstract

Encapsulation of autologous adult cartilage cells (chondrocytes) in hydrolytically degradable hydrogels may provide a clinically viable tissue engineering therapy for replacement of damaged or osteoarthritic cartilage. When designing a tissue engineering scaffold, it is crucial to evaluate adult chondrocytes due to their limited growth potential. The objective for this study was to compare extracellular matrix anabolic and catabolic metabolisms by juvenile and adult chondrocytes in hydrolytically degradable hydrogels. Cells were photo-encapsulated in bimodal degradable hydrogels composed of slow-degrading poly(ethylene glycol) (PEG) and the fast-degrading copolymer oligo(lactic acid)-b-PEG-b-oligo(lactic acid) crosslinks, and cultured through four weeks. Cell density was significantly higher in constructs containing adult cells, contributing to higher glycosaminoglycan content per wet weight. However, juvenile cells exhibited higher collagen content per cell. Immunohistochemical visualization revealed cartilage-specific aggrecan and collagen II deposition by both adult and juvenile cells. Immunohistochemically stained catabolically degraded collagen fragments and western blot-detected degraded aggrecan fragments, especially those associated with an osteoarthritic state, were more abundant in constructs with adult cells. Overall, bimodal degradable hydrogel environments were supportive of viable adult cells. However, major challenges with adult cells include their reduced collagen productivity and high catabolic activity, which may impact the quality of the engineered tissues.