Conventional synthetic vascular grafts are associated with significant failure rates due to their mismatched mechanical properties with the native vessel and poor regenerative potential.Though different tissue enginee...Conventional synthetic vascular grafts are associated with significant failure rates due to their mismatched mechanical properties with the native vessel and poor regenerative potential.Though different tissue engineering approaches have been used to improve the biocompatibility of synthetic vascular grafts,it is still crucial to develop a new generation of synthetic grafts that can match the dynamics of native vessel and direct the host response to achieve robust vascular regeneration.The size of pores within implanted biomaterials has shown significant effects on macrophage polarization,which has been further confirmed as necessary for efficient vascular formation and remodeling.Here,we developed biodegradable,autoclavable synthetic vascular grafts from a new polyurethane elastomer and tailored the grafts’interconnected pore sizes to promote macrophage populations with a pro-regenerative phenotype and improve vascular regeneration and patency rate.The synthetic vascular grafts showed similar mechanical properties to native blood vessels,encouraged macrophage populations with varying M2 to M1 phenotypic expression,and maintained patency and vascular regeneration in a one-month rat carotid interposition model and in a four-month rat aortic interposition model.This innovative bioactive synthetic vascular graft holds promise to treat clinical vascular diseases.展开更多
The objective of this work was to fabricate a rigid,resorbable and osteoconductive scaffold by mimicking the hierarchical structure of the cortical bone.Aligned peptide-functionalize nanofiber microsheets were generat...The objective of this work was to fabricate a rigid,resorbable and osteoconductive scaffold by mimicking the hierarchical structure of the cortical bone.Aligned peptide-functionalize nanofiber microsheets were generated with calcium phosphate(CaP)content similar to that of the natural cortical bone.Next,the CaP-rich fibrous microsheets were wrapped around a microneedle to form a laminated microtube mimicking the structure of an osteon.Then,a set of the osteon-mimetic microtubes were assembled around a solid rod and the assembly was annealed to fuse the microtubes and form a shell.Next,an array of circular microholes were drilled on the outer surface of the shell to generate a cortical bone-like scaffold with an interconnected network of Haversian-and Volkmann-like microcanals.The CaP content,porosity and density of the bone-mimetic microsheets were 240 wt%,8%and 1.9 g/ml,respectively,which were close to that of natural cortical bone.The interconnected network of microcanals in the fused microtubes increased permeability of a model protein in the scaffold.The cortical scaffold induced osteogenesis and vasculogenesis in the absence of bone morphogenetic proteins upon seeding with human mesenchymal stem cells and endothelial colony-forming cells.The localized and timed-release of morphogenetic factors significantly increased the extent of osteogenic and vasculogenic differentiation of human mesenchymal stem cells and endothelial colony-forming cells in the cortical scaffold.The cortical bonemimetic nature of the cellular construct provided balanced rigidity,resorption rate,osteoconductivity and nutrient diffusivity to support vascularization and osteogenesis.展开更多
基金support from NIH grants R01AR057837,U01AR069395,R01AR072613,R01AR074458 from NIAMS,and DoD grant W81XWH-20-1-0343,the Stanford Woods Institute for the Environment,and the Tad and Diane Taube Family Foundation.
文摘Conventional synthetic vascular grafts are associated with significant failure rates due to their mismatched mechanical properties with the native vessel and poor regenerative potential.Though different tissue engineering approaches have been used to improve the biocompatibility of synthetic vascular grafts,it is still crucial to develop a new generation of synthetic grafts that can match the dynamics of native vessel and direct the host response to achieve robust vascular regeneration.The size of pores within implanted biomaterials has shown significant effects on macrophage polarization,which has been further confirmed as necessary for efficient vascular formation and remodeling.Here,we developed biodegradable,autoclavable synthetic vascular grafts from a new polyurethane elastomer and tailored the grafts’interconnected pore sizes to promote macrophage populations with a pro-regenerative phenotype and improve vascular regeneration and patency rate.The synthetic vascular grafts showed similar mechanical properties to native blood vessels,encouraged macrophage populations with varying M2 to M1 phenotypic expression,and maintained patency and vascular regeneration in a one-month rat carotid interposition model and in a four-month rat aortic interposition model.This innovative bioactive synthetic vascular graft holds promise to treat clinical vascular diseases.
基金supported by research grants to E.Jabbari from the National Science Foundation under Award Numbers CBET1403545 and IIP150024 and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number AR063745.
文摘The objective of this work was to fabricate a rigid,resorbable and osteoconductive scaffold by mimicking the hierarchical structure of the cortical bone.Aligned peptide-functionalize nanofiber microsheets were generated with calcium phosphate(CaP)content similar to that of the natural cortical bone.Next,the CaP-rich fibrous microsheets were wrapped around a microneedle to form a laminated microtube mimicking the structure of an osteon.Then,a set of the osteon-mimetic microtubes were assembled around a solid rod and the assembly was annealed to fuse the microtubes and form a shell.Next,an array of circular microholes were drilled on the outer surface of the shell to generate a cortical bone-like scaffold with an interconnected network of Haversian-and Volkmann-like microcanals.The CaP content,porosity and density of the bone-mimetic microsheets were 240 wt%,8%and 1.9 g/ml,respectively,which were close to that of natural cortical bone.The interconnected network of microcanals in the fused microtubes increased permeability of a model protein in the scaffold.The cortical scaffold induced osteogenesis and vasculogenesis in the absence of bone morphogenetic proteins upon seeding with human mesenchymal stem cells and endothelial colony-forming cells.The localized and timed-release of morphogenetic factors significantly increased the extent of osteogenic and vasculogenic differentiation of human mesenchymal stem cells and endothelial colony-forming cells in the cortical scaffold.The cortical bonemimetic nature of the cellular construct provided balanced rigidity,resorption rate,osteoconductivity and nutrient diffusivity to support vascularization and osteogenesis.
