Designer injectable matrices of photocrosslinkable carboxymethyl cellulose methacrylate based hydrogels as cell carriers for gel type autologous chondrocyte implantation (GACI).

Overview

Gel-type autologous chondrocyte implantation (GACI) is the fourth-generation therapeutic strategy that has been introduced to address the limitations of earlier generation strategies, especially problems related to cell leakage upon implantation and loss of chondrocyte functionality owing to the dedifferentiation of cells in culture and fibrocartilage formation. In GACI, an injectable gel system is used, which acts as the cell carrier. However, the maintenance of the morphology and redifferentiation of chondrocytes with appropriate biofunctionality are major challenges in this technique. In this study, we prepared a photocrosslinkable injectable hydrogel based on carboxymethyl cellulose-methacrylate (CMC-MA) and polyethylene glycol diacrylate (PEGDA) and evaluated chondrocyte-matrix interactions and biofunctionality on different blend ratios of the gels with varying stiffness. Cell-matrix interaction was evaluated by immunostaining for actin filaments via phalloidin and cell adhesion markers such as focal adhesion kinase (FAK), integrin β1, and integrin αV. This study indicates that the stiffness of the substrates, along with the material chemistry, is a crucial factor when selecting an injectable gel-based system. Stiffer gels (2:8 CMC-MA/PEGDA) showed good chondrocyte cell attachment and growth with maintenance of the redifferentiated phenotype; therefore, they can be considered as an ideal matrix for GACI technique.