Type I Collagen/Hyaluronic Acid Hydrogels as Delivery System for Adipose-Derived Stem Cells for Osteoarthritis Treatment

Purpose: To improve the efficacy of stem cell therapy in treating osteoarthritis, we developed a cell-protective and cell-supporting injectable delivery system that can enhance cell retention and cellular functionalities within the target site. Methods: Adipose-derived stem cells (ADSCs) were encapsulated in semi-interpenetrating network (semi-IPN) hydrogels, composed of type I collagen with varying concentrations of collagen (3, 5, and 7 mg/mL) and low molecular weight hyaluronic acid (HA) (5 mg/mL). The hydrogels were analysed for their viscoelasticity, flow behaviour, enzymatic degradation, equilibrium water content, shrinkage, and cell encapsulation potentials. In vitro studies were performed to evaluate viability, proliferation, metabolic activity, morphology, stemness, and cytoskeletal development of the ADSCs within the hydrogels. Results: The in vitro studies showed that among other compositions, Col 5/HA 5 demonstrated better cell proliferation than Col 3/HA 5 and maintained elongated stem cell morphology compared to Col 7/HA 5. To further evaluate the effectiveness of these hydrogels with and without ADSCs in slowing down cartilage degeneration, in vivo studies were performed with Col 5/HA 5 for the treatment of rat knee OA. The reports demonstrated significant attenuation of OA related joint inflammation and cartilage degeneration using Col 5/HA 5 hydrogels. Conclusion: These results confirmed that semi-IPN type I collagen-HA hydrogel can be used as a potential candidate to improve the rate of clinical translation for stem cell therapies to treat OA. Lay Summary: In this study, an injectable delivery system that can enhance cell retention and cellular functionalities within a target site was developed to improve the efficacy of stem cell therapy in treating osteoarthritis. Adipose-derived stem cells (ADSCs) were enfolded in hydrogels, that composed of type I collagen with different concentrations of collagen (3, 5, and 7 mg/mL) and low molecular weight hyaluronic acid (HA) (5 mg/mL). The hydrogels were analysed for their physical, chemical, biological potentials, to support the development of ADSCs within the hydrogels. Findings from the in vitro studies indicated that the compositions, Col 5/HA 5 demonstrated better cell proliferation than Col 3/HA 5 and maintained elongated stem cell morphology compared to Col 7/HA 5. Furthermore, the in vivo studies demonstrated significant reduction of OA related joint inflammation and cartilage degeneration using Col 5/HA 5 hydrogels. In conclusion, these results confirmed that semi-IPN type I collagen-HA hydrogel can be used as a potential candidate to improve the rate of clinical translation for stem cell therapies of treat OA. Graphical Abstract: (Figure presented.)