Silk Composite-based Multifunctional Pellets for Controlled Drug Release toward Advanced Wound Care

Chronic wounds pose a significant challenge in clinical settings due to their high risk of infections (by a mixed population of bacterial strains) and persistent inflammation. In this scenario, personalized treatment options are crucial but are limited by the complex fabrication techniques of the existing products. To this end, calcium sulfate hemihydrate (CSH)-based cement offers rapid fabrication but lacks other essential properties for promoting healing. To overcome this, herein tannic acid (TA) was added to create a multifunctional drug delivery platform. Nonetheless, direct loading of TA led to burst release, rendering it inefficient for long-term applications. Therefore, we aimed to engineer a complex of TA with silk fibroin (SF) to achieve sustained release. In this study, a multifunctional silk/bioceramic composite-based cement was developed, intended for use in point-of-care settings. The cement was cast into pellets for further evaluation. Compared to neat pellets, the composite pellets exhibited a 7.5-fold increase in antioxidant activity and prolonged antibacterial efficacy (up to 13 days). Moreover, the implantation of the pellets showed no hallmarks of local or systemic toxicity in a rodent model. The developed multifunctional composite cement proves to be a promising solution for the personalized treatment of chronic wounds designed for application in point-of-care settings.