RESUMO
The continuous stimulation of periodontitis leads to a decrease in the number of stem cells within the lesion area and significantly impairing their regenerative capacity. Therefore, it is crucial to promote stem cell homing and regulate the local immune microenvironment to suppress inflammation for the regeneration of periodontitis-related tissue defects. Here, we fabricated a novel multifunctional bilayer nanofibrous membrane using electrospinning technology. The dense poly(caprolactone) (PCL) nanofibers served as the barrier layer to resist epithelial invasion, while the polyvinyl alcohol/chitooligosaccharides (PVA/COS) composite nanofiber membrane loaded with calcium beta-hydroxy-beta-methylbutyrate (HMB-Ca) acted as the functional layer. Material characterization tests revealed that the bilayer nanofibrous membrane presented desirable mechanical strength, stability, and excellent cytocompatibility. In vitro, PCL@PVA/COS/HMB-Ca (P@PCH) can not only directly promote rBMSCs migration and differentiation, but also induce macrophage toward pro-healing (M2) phenotype-polarization with increasing the secretion of anti-inflammatory and pro-healing cytokines, thus providing a favorable osteoimmune environment for stem cells recruitment and osteogenic differentiation. In vivo, the P@PCH membrane effectively recruited host MSCs to the defect area, alleviated inflammatory infiltration, and accelerated bone defects repair. Collectively, our data indicated that the P@PCH nanocomposite membrane might be a promising biomaterial candidate for guided tissue regeneration in periodontal applications.
Assuntos
Macrófagos , Células-Tronco Mesenquimais , Nanofibras , Nanofibras/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Animais , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Diferenciação Celular/efeitos dos fármacos , Poliésteres/química , Periodontite/terapia , Periodontite/tratamento farmacológico , Membranas Artificiais , Regeneração/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Alicerces Teciduais/química , Camundongos , Ratos , Humanos , Álcool de Polivinil/químicaRESUMO
A series of novel azoles (a-v), which are analogues of fluconazole, have been designed and synthesized as potential antifungal agents by the click reaction. The click reaction approach toward the synthesis of novel 1,2,3-triazolyl linked triazole antifungal derivatives a-v was achieved by Cu(I)-catalyzed 1,3-dipolar cycloaddition of propargylated intermediate 5 with substituted azidomethyl benzene. In addition, the target compounds tested can increase antifungal activity.
Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Triazóis/síntese química , Triazóis/farmacologia , Inibidores de 14-alfa Desmetilase/síntese química , Inibidores de 14-alfa Desmetilase/farmacologia , Catálise , Cobre , Fungos/efeitos dos fármacos , Fungos/enzimologia , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Espectrofotometria Infravermelho , Relação Estrutura-AtividadeRESUMO
A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanols (1a-v, 2a-w), which are analogues of fluconazole, have been designed and synthesized as the potential antifungal agents by the click reaction. Click reaction approach toward the synthesis of two sets of novel 1,2,3-triazolyl linked triazole antifungal derivatives 1a-v, 2a-w was achieved by Cu(I)-catalyzed 1,3-dipolar cycloaddition of propargylated intermediate 8 with substituted azidomethyl benzene. The 1,2,3-triazolyl group was inserted into the side chain of the target molecule which can increase the antifungal activity of compounds.
