Electrostatic complexation of growth factors in thiol-armed hydrogel enhances in situ cartilage tissue engineering

Tissue engineering is a promising approach to addressing the poor natural healing capacity of articular cartilage. However, the challenge is to sustain stem cells' chondrogenic differentiation post-implantation in a long-term manner. Herein, we propose the electrostatic complexation of growth factors in thiol-armed hydrogels. Transforming growth factor beta-3 (TGFB3) and bone morphogenic protein-6 (BMP6) are electrostatically complexed to poly-lysine and thiol-heparin which in turn is bound via thiol-acrylate to a gelatin methacryloyl (GelMA) hydrogel. Growth factor and dose-dependency are evaluated in human adipose-derived stem cells (hADSCs) highlighting the minimal dose and growth factor selection for triggering chondrogenic response. The efficiency of growth factor retention through the functionalized hydrogels reveals slower release compared to non-functionalised hydrogels highlighting the ability for long-term stimulation. Long-term (56 days) ex vivo evaluation of the in situ tissue engineered implant shows that our novel functionalisation strategy exhibits enhanced hyaline cartilage matrix deposition when compared to non-functionalised hydrogels. This flexible functionalisation design strategy clearly advances in situ tissue engineering for the treatment of articular cartilage injuries.