Platelet-rich plasma-loaded bioactive chitosan@sodium alginate@gelatin shell-core fibrous hydrogels with enhanced sustained release of growth factors for diabetic foot ulcer healing

The ability of autologous platelet-rich plasma (PRP) gel to promote rapid wound healing without immunological rejection has opened new avenues for the treatment of diabetic foot wounds. However, PRP gel still suffers from the quick release of growth factors (GFs) and requires frequent administration, thus resulting in decreased wound healing efficiency, higher cost as well as greater pain and suffering for the patients. In this study, the flow-assisted dynamic physical cross-linked coaxial microfluidic three-dimensional (3D) bio-printing technology, combined with the calcium ion chemical dual cross-linking method was developed to design PRP-loaded bioactive multi-layer shell-core fibrous hydrogels. The prepared hydrogels exhibited outstanding water absorption-retention capacity, good biocompatibility as well as a broad-spectrum antibacterial effect. Compared with clinical PRP gel, these bioactive fibrous hydrogels displayed a sustained release of GFs, reducing the administration frequency by 33 % availably during the wound treatment, but more prominent therapeutic effects such as effective reduced inflammation, in addition to promoting the growth of granulation tissue and angiogenesis, the formation of high-density hair follicles, and the generation of regular ordered and high-density collagen fiber network, which suggested great promise as exceptional candidates for treatment of diabetic foot ulcer in clinical settings.