Time-programmed release of curcumin and Zn 2+ from multi-layered RSF coating modified PET graft for improvement of graft-host integration.

Artificial graft serves as the primary grafts used in the clinical management of sports-related injuries. Until now, optimizing its graft-host integration remains a great challenge due to the excessive inflammatory response during the inflammatory phase, coupled with an absence of tissue-inductive capacity during the regeneration phase. Here, a multi-layered regenerated silk fibroin (RSF) coating loaded with curcumin (Cur) and Zn ²⁺ on the surface of the PET grafts (Cur@Zn ²⁺ @PET) was designed and fabricated for providing time-matched regulation specifically tailored to address issues arising at both inflammatory and regeneration phases, respectively. The release of Cur and Zn ²⁺ from the Cur@Zn ²⁺ @PET followed a time-programmed pattern in vitro. Specifically, cellular assays revealed that Cur@Zn ²⁺ @PET initially released Cur during the inflammatory phase, thereby markedly inhibit the expression of inflammatory cytokines TNF-a and IL-1β. Meanwhile, a significant release of Zn ²⁺ was major part during the regeneration phase, serving to induce the osteogenic differentiation of rBMSC. Furthermore, rat model of anterior cruciate ligament reconstruction (ACLR) showed that through time-programmed drug release, Cur@Zn ²⁺ @PET could suppress the formation of fibrous interface (FI) caused by inflammatory response, combined with significant new bone (NB) formation during regeneration phase. Consequently, the implementation of the Cur@Zn ²⁺ @PET characterized by its time-programmed release patterns hold considerable promise for improving graft-host integration for sports-related injuries.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)