Effect Of Liquid Crystal-modified Mesoporous Silica Nanoparticles On Angiogenesis Of Human Umbilical Vein Endothelial Cells

BackgroundThe healing of oral and maxillofacial soft tissue defects caused by trauma,surgery,and inflammation is still a major clinical challenge due to the interference of infection and impaired angiogenesis.Especially in the healing of chronic wounds or deep skin defects,the promotion of microvascular formation is crucial as it will provide oxygen and nutrients to the damaged tissue and relieve uncontrollable inflammation.However,inadequate induction of angiogenesis is a major limitation of existing wound dressings in tissue engineering.As a novel biomaterial,cholesteric phase liquid crystal has excellent biocompatibility and promotes endothelial cell ring formation,which is expected to promote the angiogenesis process.Thus,in this study,Liquid Crystal-Mesoporous silica nanoparticles(LC-MSN)were prepared and evaluated for biocompatibility and angiogenesis activity.In addition,a novel multifunctional gel of Chitosan/Liquid Crystal-Mesoporous silica nanoparticles(CS/LC-MSN)was developed by loading LC-MSN into chitosan,and its ability to promote tissue repair and regeneration was evaluated.ObjectiveLC-MSN and CS/LC-MSN gel were prepared to investigate their effects on the activity and angiogenic ability of human umbilical vein endothelial cells(HUVECs)in vitro,and then to verify their effects on the healing of skin defects in vivo.MethodFirstly,LC and MSN based composite were synthesized by ontology polymerization method,and the liquid crystal morphology and properties were examined by systematic characterization assays including transmission electron microscopy,scanning electron microscopy,attenuated total reflectance-fourier transformation infrared,dynamic light scattering,and polarizing optical microscopy.To verify biocompatibility of LC-MSN composite,cell proliferation,live/dead staining assay,wound scratch testing,and cell morphology assay of HUVECs were performed.Next,angiogenesis activity was first investigated by tube formation assay,qRT-PCR and Western blot in vitro.Eventually,CS/LC-MSN gel was fabricated and full-thickness skin defects in rats were developed.The wound closure percentage,H&E staining,Masson’s trichrome staining and immunohistochemistry were performed to assess the healing-promoting and vascularizing abilities of this composite gel in vivo.Results1.Cholesteric phase liquid crystal and mesoporous silica nanoparticles were successfully prepared,and then LC-MSN system with liquid crystal properties were synthesized.2.A certain concentration of LC-MSN showed good cytocompatibility and promoted cell spreading and migration.3.LC-MSN at a concentration of 18.8 μg/mL not only promoted the formation of tube in HUVECs,but also increased the expression of angiogenesis-related genes and proteins.4.CS/LC-MSN gel improved wound repair by alleviating inflammation and promoting the process of re-epithelialization,collagen deposition as well as angiogenesis.ConclusionCS/LC-MSN gel provides both biological activity of LC-MSN and mechanical advantages of hydrogel,with good biocompatibility and pro-vascularization activity.Thus,it is expected to be a promising biomedical dressing.