RESUMO
The objective of this study was to fabricate and characterize chitosan combined with different amounts of simvastatin-loaded nanoparticles and to investigate their potential for guided bone regeneration in vitro and in vivo. Different SIM-CSN formulations were combined into a chitosan scaffold (SIM-CSNs-S), and the morphology, simvastatin release profile, and effect on cell proliferation and differentiation were investigated. For in vivo experiments, ectopic osteogenesis and the critical-size cranial defect model in SD rats were chosen to evaluate bone regeneration potential. All three SIM-CSNs-S formulations had a porous structure and exhibited sustained simvastatin release. CSNs-S showed excellent degradation and biocompatibility characteristics. The 4 mg SIM-CSNs-S formulation stimulated higher BMSC ALP activity levels, demonstrated significantly earlier collagen enhancement, and led to faster bone regeneration than the other formulations. SIM-CSNs-S should have a significant effect on bone regeneration.
Assuntos
Regeneração Óssea/efeitos dos fármacos , Quitosana/química , Regeneração Tecidual Guiada/métodos , Nanopartículas/química , Nanopartículas/metabolismo , Sinvastatina/farmacocinética , Alicerces Teciduais/química , Animais , Osso e Ossos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/metabolismo , Preparações de Ação Retardada , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Composição de Medicamentos , Masculino , Teste de Materiais , Microesferas , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Ratos , Ratos Sprague-Dawley , Sinvastatina/administração & dosagem , Propriedades de Superfície , Engenharia Tecidual/métodosRESUMO
This study aimed to develop of a rapid and effective method to occlude dentinal tubules using carboxymethyl chitosan and lysozyme (CMC/LYZ) nanogels with encapsulated amorphous calcium phosphate (ACP) based on the transformation of ACP to HAP. In this work, CMC/LYZ was used to stabilize ACP and form CMC/LYZ-ACP nanogels, and then the nanogel-encapsulated ACP was applied to exposed dentinal tubule surfaces. The morphology of the nanogels was examined by transmission electron microscopy (TEM). Distribution and quantity of elements in CMC/LYZ-ACP nanogels were determined by element mapping and energy dispersive X-Ray spectroscopy (EDX). Scanning electron microscopy (SEM) images, XRD measurements and nanoindentation were applied to check the efficacy of tubular occlusion. TEM revealed that CMC/LYZ-ACP nanogels were spherical dense gel particles with size approximately 50-500 nm. Element mapping and EDX indicated that C, N, O, Ca, P, and S in the microspheres are thoroughly represented. SEM images shows that the thickness of the coating layer was approximately 1-2 µm and the depth to which the mineralized substance enters the dentinal tubule was approximately 4-8 µm. XRD measurements and nanoindentation indicated that the occluding mineralized substance observed were similar to nature dentin. CMC can form spherical dense nanogels loaded with ACP under the participation of lysozyme. The CMC/LYZ-ACP nanogels could increase the dentinal tubule occluding effectiveness. These results indicated that finding and developing novel nanomaterials of CMC/LYZ-ACP would be an effective strategy for the treatment of dentin hypersensitivity.