Silk Composite-Based Multifunctional Pellets for Controlled Release

Abstract

Chronic wounds present significant clinical challenges due to the high risk of infections and persistent inflammation. While personalized treatments in point-of-care settings are crucial, they are limited by the complex fabrication techniques of the existing products. The calcium sulfate hemihydrate (CSH)-based drug delivery platform enables rapid fabrication but lacks antioxidant and antibacterial properties, essential to promote healing. To develop a multifunctional platform, a tannic acid (TA)-silk fibroin (SF) complex is engineered and incorporated as an additive in CSH cement. This cement is then cast into pellets to create silk/bioceramic-based composite drug delivery systems, designed for point-of-care use. Compared to neat CSH pellets, the composite pellets exhibit a 7.5-fold increase in antioxidant activity and prolonged antibacterial efficacy (up to 13 d). Moreover, the subcutaneous implantation of the pellets shows no hallmarks of local or systemic toxicity in a rodent model. The pellets are optimized in composition and fabrication to ease market translation. Clinically, the pellets have the potential to be further developed into products to place on wound beds or fill into bone cavities that are designed to deliver the intended therapeutic effect. The developed multifunctional system proves to be a promising solution for personalized treatment in point-of-care settings.