Triple PLGA/PCL scaffold modification including silver-impregnation, collagen-coating, and electrospinning significantly improve biocompatibility, antimicrobial, and osteogenic properties for oro-facial tissue regeneration.

Biodegradable synthetic scaffolds hold great promise for oral and craniofacial guided tissue regeneration and bone regeneration. To overcome the limitations of current scaffold materials in terms of osteogenic and antimicrobial properties, we have developed a novel silver-modified/collagen-coated electrospun PLGA/PCL scaffold (PP-pDA-Ag-COL) with improved antimicrobial and osteogenic properties. Our novel scaffold was generated by electrospinning a basic PLGA/PCL matrix, followed by silver nanoparticle (AgNPs) impregnation via in situ reduction and polydopamine coating, and then coated by collagen I. The three intermediate materials involved in the fabrication of our scaffolds, PLGA/PCL (PP), PLGA/PCL-polydopamine (PP-pDA), and PLGA/PCL-polydopamine-Ag (PP-pDA-Ag) were used as control scaffolds. Scanning electron micrographs and mechanical testing indicated that the unique 3-dimensional structures with randomly-oriented nanofibrous electrospun-scaffold architectures, the elasticity modulus and the tensile strength were maintained after modifications. CCK-8 cell proliferation analysis demonstrated that the PP-pDA-Ag-COL scaffold was associated with higher MC3T3 proliferation rates than the three control scaffolds employed. Scanning electron and fluorescence light microscopy illustrated that PP-pDA-Ag-COL scaffolds significantly enhanced MC3T3 cell adhesion compared to the control scaffolds after 12h and 24h culture, in tandem with the highest β1 integrin expression levels, both at the mRNA level and the protein level. ALP activity, BMP2 and RUNX2 expression levels of MC3T3 cells cultured on PP-pDA-Ag-COL scaffolds for 7 and 14 days were also significantly higher when compared to controls (P < 0.001). There was a wider antibacterial zone associated in PP-pDA-Ag-COL and PP-pDA-Ag scaffolds versus control scaffolds (P < 0.05), and bacterial fluorescence was reduced on the Ag-modified scaffolds after 24h inoculation against S. aureus and S. mutans. In a mouse periodontal disease model, the PP-pDA-Ag-COL scaffold enhanced alveolar bone regeneration (31.8%) and was effective for periodontitis treatment. These results demonstrate that our novel PP-pDA-Ag-COL scaffold enhanced biocompatibility, osteogenic and antibacterial properties and has therapeutic potential for alveolar/craniofacial bone regeneration.