Developing Bioactive Hydrogels Containing Cell-derived Extracellular Matrix for Bone and Cartilage Repair
Abstract
The prevalence of osteoarthritis (OA) has been increasing in ageing populations, which has necessitated the use of advanced biomedical treatments. These involve grafts or delivering drug molecules entrapped in scaffolds. However, such treatments often show suboptimal therapeutic effects due to poor half-life and off-target effects of drug molecules. This study aimed to overcome limitations associated with current treatments for OA and osteochondral defects by combining decellularized extracellular matrix (ECM) with gelatin methacryloyl (GelMA) and utilizing digital light processing (DLP) 3D printing. GelMA has shown great potential in tissue engineering due to biocompatibility and mechanical tunability. To harvest bioactive ECM, pre-osteoblastic and pre-chondrogenic mice cells were cultured in vitro and differentiated for 14 days. Decellularized ECM from these cell lines were incorporated into GelMA hydrogels to fabricate GelO and GelC hydrogels with osteogenic and chondrogenic properties, respectively. The concentrations of decellularized ECM in the hydrogels were optimized for cytocompatibility and differentiation potential. Additionally, mechanical and rheological properties, swelling, and degradation behaviour of the different hydrogel formulations were assessed. We demonstrated when human adult stem cells are grown on ECM-hydrogels (GelO or GelC) individually or in combination (GelO-GelC) for 21 days can induce osteogenic and chondrogenic differentiation as confirmed by staining techniques (Alizarin Red S and Alcian Blue S) and qPCR analysis for corresponding gene markers. Additionally, we showed that formulated ECM-hydrogels can be chemically bonded using carbodiimide-based coupling reactions to mimic the osteochondral interface. To conclude, this ECM-based bioactive hydrogel offers a promising new drug-free and cell-free treatment strategy for bone and cartilage repair, and future OA management.