Methacrylated gelatin shape-memorable cryogel subcutaneously delivers EPCs and aFGF for improved pressure ulcer repair in diabetic rat model

Pressure ulcer (PU) in patients with diabetes mellitus (DM) is still a clinical intractable issue due to the complicated physiological characteristics by the prolonged high glucose level and impaired angiogenesis. The PU treatment includes surgical debridement, stem cell therapy and growth factors, leading to high cost and repeated professional involvement. Developing effective wound dressing combining the therapeutic cells and growth factors has become highly demanded. Herein, we reported the direct subcutaneous administration of endothelial progenitor cells (EPCs) and acid fibroblast growth factor (aFGF) with a shape-memorable methacrylated gelatin cryogel (EPCs/aFGF@GelMA) for the therapy of PU in rats with DM. This EPCs/aFGF@GelMA cryogel system presented microporous structure, elastic mechanical strength and enhanced cell migration property with controlled release of aFGF. Moreover, compared with EPCs/aFGF and GelMA alone, in vivo results showed that this EPCs/aFGF@GelMA system exhibited accelerated wound closure rate, enhanced granulation formation, collagen deposition as well as re-epithelization. Importantly, we found that the excellent positive performance of EPCs/aFGF@GelMA is due to its up-regulation of HIF-a upon the wound site, modulating the microenvironment of wound site to initiate the impaired local angiogenesis. Collectively, this hybrid gelatin cryogels show great promise for biomedical applications, especially in tissue engineering and regenerative medicine.

Automated summary

This study reported the use of a shape-memorable methacrylated gelatin cryogel for the direct subcutaneous administration of endothelial progenitor cells (EPCs) and acid fibroblast growth factor (aFGF) for the treatment of pressure ulcers in diabetic rats. The cryogel system had a microporous structure, elastic mechanical strength, enhanced cell migration property, and controlled release of aFGF. In vivo results showed that the cryogel system accelerated wound closure rate, enhanced granulation formation, collagen deposition, and re-epithelization. The excellent performance of the cryogel system was attributed to its up-regulation of HIF-a, which modulated the impaired local angiogenesis. This hybrid gelatin cryogels hold great promise for biomedical applications, particularly in tissue engineering and regenerative medicine.