Poly lactic‐co‐glycolic acid scaffold loaded with plasmid DNA encoding fibroblast growth factor‐2 promotes periodontal ligament regeneration of replanted teeth

Abstract

ObjectiveThis 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.BackgroundGrowth 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.MethodsIn 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.ResultsThe 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 123 ng pFGF‐2 over 21 days 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.ConclusionsThe 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.

Elements of 3D Bioprinting in Periodontal Regeneration: Frontiers and Prospects

“…In the dog periodontal defect model, researchers placed PLGA and PLGA/FGF-2 scaffolds made by electrospinning and the formation of organized periodontal ligament-like tissue was observed. Meanwhile, in vitro, the PLGA/FGF-2 scaffolds can promote the proliferation of PDLSCs [60].…”

“…Cell electrospinning receives much attentions as it can fabricate biomimicry scaffolds [76]. Electrospinning fabricated PLGA scaffolds loaded with FGF-2 could release FGF-2 continuously within 21 days and promote the proliferation of PDLSCs [60]. Based on the different principles of various 3D bioprinting techniques, strength and limitations are list as follows [73,77,78].…”

“…The oral and maxillofacial region has been considered as a rich source of adult stem cells. Several studies and animal trials have proven that stem cells can perform a promising role in periodontal regeneration [20,24,35,38,47,60]. Due to individual heterogeneity, the reaction to implantation and technique sensitivity, the success rate of stem cells is uncertain and the clinical gain of the treatment differs according to different situations.…”

Biodegradable engineered fiber scaffolds fabricated by electrospinning for periodontal tissue regeneration

“…As mentioned above, electrospinning has been used in providing vectors for gene delivery, in which target gene materials can be injected into and around the wound to infect the host cells, enabling them to produce the therapeutic proteins. 170 However, considering that plasmids showed long expression time and uncertain transfection efficiency 160,165 and the expensive price of electrospinning gene loading, this technology has little significance in periodontal clinical application at present.…”

“…The scaffold promoted the proliferation of hPDLCs as expected and increased the expression levels of collagen I and scleraxis, resulting in more regular PDL-like tissues regeneration and less of root surface resorption. 165 Others such as platelet-derived growth factor (PDGF), 166 human epidermal growth factor (hEGF) 167 can also be incorporated into nanofibers for tissue regeneration. Besides, dual growth factor loaded scaffold which could differentially release growth factors were also fabricated to promote neovascularisation and new bone formation.…”