Simultaneous regeneration of epithelial and bone tissue using a multifunctional film with leaf-stacked structures and growth factors

Although guided bone regeneration (GBR) membranes are frequently utilized in oral-maxillofacial surgery, there continues to be a demand for membranes that can concurrently facilitate epithelial sealing and bone regeneration. In this work, a multilayered polycaprolactone (PCL) film, incorporating a central dense barrier layer and leaf-stacked structure layers on both surfaces for cell/tissue adhesion and bioactive molecule loading (MFLSS), was produced <i>via</i> a heating-cooling method using tetraglycol. Platelet-derived growth factor-BB (PDGF-BB) and bone morphogenetic protein-2 (BMP-2) were incorporated into the porous leaf-stacked layers on each side to promote epithelial and bone tissue regeneration, respectively. The PDGF-BB and BMP-2 embedded in the leaf-stacked layers were released in a sustained manner at therapeutic concentrations for 15 and 17 days, respectively. <i>In vitro</i> and <i>in vivo</i> assays indicated that the PDGF-BB-loaded layer significantly improves cell/tissue adhesion as well as cell migration, while the BMP-2-immobilized layer effectively induces osteogenic differentiation and bone formation. Collectively, these findings indicate that the multifunctional film serves as a promising GBR membrane by consistently sealing the defect site and accelerating bone healing.