Abstract
This study investigated the effects of poly lactic-co-glycolic acid (PLGA) loaded with plasmid DNA encoding fibroblast growth factor-2 (pFGF-2) on human periodontal ligament cells (hPDLCs) in vitro and evaluated the ability of the PLGA/pFGF-2 scaffold to promote periodontal ligament (PDL) regeneration in a beagle dog teeth avulsion animal model. Growth factor and scaffold play important roles in PDL regeneration. PLGA is a kind of biodegradable and biocompatible polymer that can be used as a carrier to deliver growth factors or genes. FGF-2 can induce potent proliferative responses, promote cell migration and regulate the production of extracellular matrix. Therefore, a gene-activated matrix composed of scaffold and genes is supposed to be a superior approach for promoting tissue regeneration. In this study, PLGA and PLGA/pFGF-2 scaffolds were fabricated using electrospinning. The characterization of scaffolds was shown by scanning electron microscope (SEM) and transmission electron microscope (TEM). dsDNA HS was used to test the plasmid release of PLGA/pFGF-2 scaffold. The viability and proliferation of hPDLCs on the two kinds of scaffolds were evaluated by the CCK-8 assay, and the expression of collagen I and scleraxis were analysed by RT-qPCR. The roots of avulsed teeth were covered by the two types of scaffolds and replanted into the alveolar pockets in beagles. Haematoxylin-eosin and Masson staining were used to evaluate the effects of PLGA/pFGF-2 scaffold on promoting PDL regeneration. The smooth and uniform fibres can be observed in both scaffolds, and the plasmids were randomly distributed in the PLGA/pFGF-2 scaffold. dsDNA HS analysis demonstrated that the PLGA/pFGF-2 scaffold released up to 123ng pFGF-2 over 21days in a sustained manner without any obvious burst release. The PLGA/pFGF-2 scaffold promoted the proliferation of hPDLCs and increased the expression levels of collagen I and scleraxis compared with PLGA scaffold. Animal experiments showed that more regular PDL-like tissues and less root surface resorption occurred in the PLGA/pFGF-2 scaffold group compared with the PLGA scaffold group. The PLGA/pFGF-2 scaffold promoted hPDLCs proliferation and facilitated periodontal ligament-related differentiation. The PLGA/pFGF-2 scaffold possesses excellent biological characteristics and could be used as a promising biomaterial for improving the treatment prognosis of replanted tooth.
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