Engineering antibacterial shrinkage‐free trinary PLGA‐based  GBR membrane for bone regeneration

Abstract

The purpose of this study was preparation of a multilayer electrospun poly (lactic‐co‐glycolic acid) (PLGA)‐based guided bone regeneration (GBR) membrane with controlled shrinkage behavior and alveolar bone regeneration property. First, PLGA copolymer, and zinc‐doped hydroxyapatite (Zn‐HAp) particles were prepared and characterized using fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), proton nuclear magnetic resonance, and X‐ray diffraction analysis. Since the electrospun PLGA scaffolds showed about 80% shrinkage at physiological conditions (phosphate‐buffered saline, 37°C), the effect of factors such as fiber‐alignment, and additives including natural polymers such as gelatin and chitosan, and Zn‐HAp particles; as well as solution preparation method was investigated on the shrinkage ratio. The results showed that it is possible to eliminate the shrinkage of the scaffold in the physiological environment through appropriate design of a tri‐layer PLGA‐CHI/PLGA‐Gel/PLGA‐Gel‐ZnHAp membrane. The designed tri‐layer membrane demonstrated a bubble point smaller than 7 μm, and improved mechanical properties compared with the individual sub‐layer scaffolds. Additionally, it exhibited enhanced antibacterial activity when compared with a similar three‐layer membrane in which HAp was used instead of Zn‐HAp. This observation suggests a synergistic antibacterial effect resulting from the presence of both zinc ions in Zn‐HAp and chitosan . Osteogenic differentiation of adipose‐derived mesenchymal stem cells cultured on the optimal multilayer composite scaffold, was investigated using alkaline phosphatase and Alizarin red staining assays, and the results suggested that the scaffold could support osteogenic differentiation of the stem cells. The designed membrane was implanted in critical size (1 cm) mandibular defects in dogs, and bone regeneration was monitored by computed tomography. Defects treated with the GBR membrane, and the control group showed 69.31% and 44.63%, newly mineralized tissue, respectively, after 8 weeks post implantation. Based on our results, the engineered 3‐layer scaffold is a promising candidate as a GBR membrane for periodontal applications.

Recent trends in bone tissue engineering: a review of materials, methods, and structures

“…Alizarin red staining and ALP assays showed the osteogenic differentiation of AT-MSCs on composite scaffolds. Additionally, using these composites, successful bone regeneration was observed in critical-sized mandibular defects in dogs in in-vivo tests [205]. In 3D-printed high-ceramic content composites of PCL and HAp, alkali surface modification was utilized to enhance the surface hydrophilicity of the PCL/hyaluronic acid scaffold, and regulate the immune responses.…”