Injectable chitosan-based thermosensitive hydrogel loaded with adipose-derived mesenchymal stem cells promotes pressure ulcer healing

Abstract

Pressure ulcers, resulting from prolonged external pressure or shear forces on skin and underlying tissues over bony prominences, lead to tissue ischemia and impaired lymphatic drainage. Without timely intervention, these wounds can progress to severe complications including cellulitis, chronic infections, and osteomyelitis. In this study, we developed a chitosan/sodium β-glycerophosphate/gelatin (CS/β-GP/GEL) thermosensitive hydrogel system to enhance the therapeutic efficacy of adipose-derived mesenchymal stem cells (ADSCs) in pressure ulcer healing. The incorporation of gelatin addresses the limitations of conventional CS/β-GP hydrogels, such as low mechanical strength and poor biocompatibility. The optimized CS/β-GP/GEL hydrogel exhibits good injectability, suitable gel formation time and pH, facilitating efficient ADSCs encapsulation. Furthermore, the hydrogel demonstrates good water absorption capacity, degradability, and rheological properties, making it suitable for biomedical applications. In vitro studies confirmed the hydrogel's high cytocompatibility, supporting ADSCs viability and proliferation. Additionally, the CS/β-GP/GEL@ADSC composite demonstrated pro-angiogenic properties, suppressed reactive oxygen species-mediated apoptosis, and facilitated the accumulation of M2-type macrophages. In vivo evaluations revealed that the CS/β-GP/GEL@ADSC composite had high histocompatibility and accelerated pressure ulcer healing in a rat model, mediated through enhanced angiogenesis, M2-dominant macrophage polarization, and improved extracellular matrix remodeling. These findings highlight the potential of CS/β-GP/GEL@ADSC as a promising therapeutic strategy for pressure ulcer management.