Fast-gelling gellan gum-based microparticulate powder for the treatment of complex cutaneous wounds

Hard-to-heal complex wounds remain a clinical challenge due to the involvement of multiple tissue types and limited accessibility. In this study, gellan gum (GG)-based dry microparticulate powders were synthesized via spray-drying, incorporating hyaluronic acid (HA) to promote skin healing or hydroxyapatite (HAp) to support bone repair, for the targeted treatment of complex wounds involving both soft tissue and bone. The microparticles, with an average size of 2-3 μm, rapidly formed gel-like structures upon hydration, retaining up to 20 % of their original mass. Injectable formulations developed by loading GG-based microparticles in a GG vehicle solution enabled extrusion through 18G and 25G needles, with the added benefit of ionic crosslinking for enhanced retention at the wound site, such as in interdigital spaces. Degradation studies under pH conditions mimicking different healing stages showed progressive release of calcium and phosphate ions from HAp-containing formulations, along with basification of the medium. These degradation by-products may have beneficial effects on skin and bone healing, as supported by the positive effect of microparticles on the viability and proliferation of human osteoblast, dermal fibroblast and keratinocyte cell lines. Our findings suggest that off-the-shelf, fast-gelling GG-based microparticulate powders possess features suitable for cutaneous wound treatment. Furthermore, the combined use of GG-HA and GG-HAp microparticles offers a promising dual strategy for addressing both skin and bone repair in complex wounds.