Interaction of Biodegradable Recombinant Honeybee Silk Films With Acute Wound Healing Processes In Vivo

Advanced wound care increasingly demands materials that can both integrate safely with tissue and support next-generation programmable functions. Recombinant protein biomaterials offer unique opportunities for designing adaptive wound dressings; however, their inherent susceptibility to host proteases presents a critical challenge, as protein-based materials may act as competitive substrates that alter proteolytic flux and potentially impede healing. Here, recombinant honeybee silk (F1-4) films were evaluated for protease susceptibility and biocompatibility, and wound-healing effects were assessed in a preclinical murine excisional wound model. The material was well tolerated, with no adverse events and no detrimental impact on final wound closure or early scar formation. Subtle, transient effects were observed during the inflammatory and proliferative phases, including modestly slower wound closure between days 7-13 and thinner epidermal coverage at day 14, with histological differences most pronounced at day 7. While recombinant honeybee silk was susceptible to host-relevant proteases in vitro, protease activity was not directly measured in wound tissue or exudate. Therefore, the observed transient differences in healing are consistent with, but do not establish, the hypothesis that the material may act as a modest competitive substrate during the proliferative phase. Importantly, this did not impair overall healing outcomes. Together, these results establish foundational safety evidence and highlight recombinant honeybee silk as a promising platform for engineering advanced, responsive healthcare materials for clinical wound management.