RESUMO
The recent development of nanobiomaterials has shed some light on the field of periodontal tissue regeneration. Laponite (LAP), an artificially synthesized two-dimensional (2D) disk-shaped nanosilicate, has garnered substantial attention in regenerative biomedical applications owing to its distinctive structure, exceptional biocompatibility and bioactivity. This study endeavors to comprehensively evaluate the influence of LAP on periodontal regeneration. The effects of LAP on periodontal ligament cells (PDLCs) on osteogenesis, cementogenesis and angiogenesis were systematically assessed, and the potential mechanism was explored through RNA sequencing. The results indicated that LAP improved osteogenic and cementogenic differentiation of PDLCs, the regulatory effects of LAP on PDLCs were closely correlated with activation of PI3K-AKT signaling pathway. Moreover, LAP enhanced angiogenesis indirectly via manipulating paracrine of PDLCs. Then, LAP was implanted into rat periodontal defect to confirm its regenerative potential. Both micro-CT and histological analysis indicated that LAP could facilitate periodontal tissue regeneration in vivo. These findings provide insights into the bioactivity and underlying mechanism of LAP on PDLCs, highlighting it might be a potential therapeutic option in periodontal therapy.
Assuntos
Diferenciação Celular , Osteogênese , Ligamento Periodontal , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Regeneração , Transdução de Sinais , Silicatos , Ligamento Periodontal/citologia , Ligamento Periodontal/metabolismo , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ratos , Osteogênese/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Silicatos/farmacologia , Silicatos/química , Humanos , Diferenciação Celular/efeitos dos fármacos , Masculino , Células Cultivadas , CementogêneseRESUMO
Although various new biomaterials have enriched the methods for periodontal regeneration, their efficacy is still controversial, and the regeneration of damaged support tissue in the periodontium remains challenging. Laponite (LAP) nanosilicate is a layered two-dimensional nanoscale, ultrathin nanomaterial with a unique structure and brilliant biocompatibility and bioactivity. This study aimed to investigate the effects of nanosilicate-incorporated PCL (PCL/LAP) nanofibrous membranes on periodontal ligament cells (PDLCs) in vitro and periodontal regeneration in vivo. A PCL/LAP nanofibrous membrane was fabricated by an electrospinning method. The characterization of PCL/LAP nanofibrous membrane were determined by scanning electron microscopy (SEM), energy dispersive spectrum of X-ray (EDS), inductively coupled plasma mass spectrometry (ICP-MS) and tensile test. The proliferation and osteogenic differentiation of PDLCs on the PCL/LAP nanofibrous membrane were evaluated. A PDLCs and macrophage coculture system was used to explore the immunomodulatory effects of the PCL/LAP nanofibrous membrane. PCL/LAP nanofibrous membrane was implanted into rat calvarial and periodontal defects, and the regenerative potential was evaluated by microcomputed topography (micro-CT) and histological analysis. The PCL/LAP nanofibrous membrane showed good biocompatibility and bioactivity. It enhanced the proliferation and osteogenic differentiation of PDLCs. The PCL/LAP nanofibrous membrane also stimulated anti-inflammatory and pro-remodeling N2 neutrophil formation, regulated inflammatory responses and induced M2 macrophage polarization by orchestrating the immunomodulatory effects of PDLCs. The PCL/LAP nanofibrous membrane promoted rat calvarial defect repair and periodontal regeneration in vivo. LAP nanosilicate-incorporated PCL membrane is capable of mediating osteogenesis and immunomodulation of PDLCs in vitro and accelerating periodontal regeneration in vivo. It could be a promising biomaterial for periodontal regeneration therapy.
Assuntos
Nanofibras , Ligamento Periodontal , Ratos , Animais , Osteogênese , Materiais Biocompatíveis/farmacologia , Diferenciação Celular , Imunomodulação , Regeneração , Alicerces Teciduais/químicaRESUMO
Critical oral-maxillofacial bone defects, damaged by trauma and tumors, not only affect the physiological functions and mental health of patients but are also highly challenging to reconstruct. Personalized biomaterials customized by 3D printing technology have the potential to match oral-maxillofacial bone repair and regeneration requirements. Laponite (LAP) nanosilicates have been added to biomaterials to achieve biofunctional modification owing to their excellent biocompatibility and bioactivity. Herein, porous nanosilicate-functionalized polycaprolactone (PCL/LAP) was fabricated by 3D printing technology, and its bioactivities in bone regeneration were investigated in vitro and in vivo. In vitro experiments demonstrated that PCL/LAP exhibited good cytocompatibility and enhanced the viability of bone marrow mesenchymal stem cells (BMSCs). PCL/LAP functioned to stimulate osteogenic differentiation of BMSCs at the mRNA and protein levels and elevated angiogenic gene expression and cytokine secretion. Moreover, BMSCs cultured on PCL/LAP promoted the angiogenesis potential of endothelial cells by angiogenic cytokine secretion. Then, PCL/LAP scaffolds were implanted into the calvarial defect model. Toxicological safety of PCL/LAP was confirmed, and significant enhancement of vascularized bone formation was observed. Taken together, 3D-printed PCL/LAP scaffolds with brilliant osteogenesis to enhance bone regeneration could be envisaged as an outstanding bone substitute for a promising change in oral-maxillofacial bone defect reconstruction.