Time-programmed Release of Curcumin and Zn2+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 Zn2+ 2 + on the surface of the PET grafts (Cur@Zn2+@PET) 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 Zn2+ 2 + from the Cur@Zn2+@PET 2 + @PET followed a time-programmed pattern in vitro. Specifically, cellular assays revealed that Cur@Zn2+@PET 2 + @PET initially released Cur during the inflammatory phase, thereby markedly inhibit the expression of inflammatory cytokines TNF-a and IL-1(3. Meanwhile, a significant release of Zn2+ 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@Zn2+@PET 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@Zn2+@PET 2 + @PET characterized by its time-programmed release patterns hold considerable promise for improving graft-host integration for sports-related injuries.