Functionally graded membranes (FGM) with regenerative signals and nanofibrous topography mimicking the native extracellular matrix have been shown to improve the outcome of alveolar ridge regeneration (ARR). This study developed a novel FGM with doxycycline-enamel matrix derivative (EMD) nanofibrous composites deposition to coordinate anti-inflammation and differentiation signals, thus facilitating ARR. Doxycycline-loaded PDLLA nanofibers (PD), EMD-loaded chitosan nanospheres (CE), and CE-embedded PD (CE-PD) were fabricated by electrospinning, deposited on the surfaces of barrier membrane to develop a FGM, and the efficacy was validated by delivering the FGM to regenerate experimental alveolar ridge defects in rats. Results revealed that PD had potent antibacterial capability, and CE-PD allowed sustained release of EMD to promote osteogenesis in vitro. In the alveolar ridge defects, FGM with PD on the outer surface downregulated MMP-8, and wound dehiscence was further reduced with Cbfa1 upregulation in those treated by FGM with CE-PD on the inner surface at 1 week. FGM with CE-PD revealed significantly greater new bone formation and defect fill at 4 weeks. In conclusion, FGM with PD reduced early tissue breakdown and with CE-PD nanofibrous composites accelerated wound healing and facilitated osteogenesis, and thus could be an advantageous strategy for ARR.
Keywords: Alveolar ridge augmentation; Doxycycline; Enamel matrix proteins; Nanocomposites; Tissue engineering.
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