Enhancing Periodontal Ligament Regeneration via PDLSC Delivery Using Electrospun PCL/Collagen/ Cellulose Acetate Scaffolds and Collagen Hydrogel Incorporated with Curcumin-Loaded ZIF-8 Nanoparticles

Abstract

Background: Regenerating periodontal ligament (PDL) tissue is a vital challenge in dentistry that aims to restore periodontal function and aesthetics. This study explores a tissue engineering strategy that combines polycaprolactone (PCL)/collagen/cellulose acetate electrospun scaffolds with collagen hydrogels to deliver curcumin-loaded ZIF-8 nanoparticles fand periodontal ligament stem cells (PDLSCs). Methods: Scaffolds were fabricated via electrospinningand collagen hydrogels incorporated PDLSCs and curcumin-loaded ZIF-8 nanoparticles (CURZIF-8) were developed using cross-linking. In vitro assays evaluated biocompatibility, anti-inflammatory, and antioxidative properties. In vivo efficacy was assessed in a rat PDL injury model using histological and ELISA analyses examining tissue regeneration and inflammatory cytokine modulation. Results: In vitro studies demonstrated that the scaffolds effectively supported PDLSC viability and migration. CURZIF-8 hydrogels enhanced anti-inflammatory and antioxidative activities. In vivo study showed that the combined scaffold-hydrogel system significantly promoted PDL regeneration. Tissue levels of bFGF, HGF, and TGF-β that are crucial for tissue repair, angiogenesis, and cell proliferation were evaluated. Whereas, pro-inflammatory cytokines TNF-α and IL-6=were downregulated. Histological analysis confirmed the formation of organized PDL structures and improved bone-cementum integration that arekey indicators of successful periodontal regeneration. Conclusion: The developed scaffold-hydrogel system facilitates PDL regeneration by modulating inflammation and promoting pro-healing factor expression. This approach shows promise for advancing periodontal tissue engineering and warrants further investigation in clinical settings.