Vascular grafts must avoid negative inflammatory responses and thrombogenesis to prohibit fibrotic deposition immediately upon implantation and promote the regeneration of small diameter blood vessels(<6 mm inner d...Vascular grafts must avoid negative inflammatory responses and thrombogenesis to prohibit fibrotic deposition immediately upon implantation and promote the regeneration of small diameter blood vessels(<6 mm inner diameter).Here,polyurethane(PU)elastomers incorporating anti-coagulative and anti-inflammatory Gastrodin were fabricated.The films had inter-connected pores with porosities equal to or greater than 86%and pore sizes ranging from 250 to 400μm.Incorporation of Gastrodin into PU films resulted in desirable mechanical properties,hydrophilicity,swelling ratios and degradation rates without collapse.The released Gastrodin maintained bioactivity over 21 days as assessed by its anti-oxidative capability.The Gastrodin/PU had better anti-coagulation response(less observable BSA,fibrinogen and platelet adhesion/activation and suppressed clotting in whole blood).Red blood cell compatibility,measured by hemolysis,was greatly improved with 2Gastrodin/PU compared to other Gastrodin/PU groups.Notably,Gastrodin/PU upregulated anti-oxidant factors Nrf2 and HO-1 expression in H2O2 treated HUVECs,correlated with decreasing pro-inflammatory cytokines TNF-αand IL-1β in RAW 264.7 cells.Upon implantation in a subcutaneous pocket,PU was encapsulated by an obvious fibrous capsule,concurrent with a large amount of inflammatory cell infiltration,while Gastrodin/PU induced a thinner fibrous capsule,especially 2Gastrodin/PU.Further,enhanced adhesion and proliferation of HUVECs seeded onto films in vitro demonstrated that 2Gastrodin/PU could help cell recruitment,as evidenced by rapid host cell infiltration and substantial blood vessel formation in vivo.These results indicate that 2Gastrodin/PU has the potential to facilitate blood vessel regeneration,thus providing new insight into the development of clinically effective vascular grafts.展开更多
The development of functional materials for osteoporosis is ultimately required for bone remodeling.However,grafts were accompanied by increasing pro-inflammatory cytokines that impaired bone formation.In this work,na...The development of functional materials for osteoporosis is ultimately required for bone remodeling.However,grafts were accompanied by increasing pro-inflammatory cytokines that impaired bone formation.In this work,nano-hydroxyapatite(n-HA)/resveratrol(Res)/chitosan(CS)composite microspheres were designed to create a beneficial microenvironment and help improve the osteogenesis by local sustained release of Res.Study of in vitro release confirmed the feasibility of n-HA/Res/CS microspheres for controlled Res release.Notably,microspheres had anti-inflammatory activity evidenced by the decreased expression of pro-inflammatory cytokines TNF-α,IL-1βand iNOS in RAW264.7 cells in a dose dependent manner.Further,enhanced adhesion and proliferation of BMSCs seeded onto microspheres demonstrated that composite microspheres were conducive to cell growth.The ability to enhance osteo-differentiation was supported by up-regulation of Runx2,ALP,Col-1 and OCN,and substantial mineralization in osteogenic medium.When implanted into bone defects in the osteoporotic rat femoral condyles,enhanced entochondrostosis and bone regeneration suggested that the n-HA/Res/CS composite microspheres were more favorable for impaired fracture healing.The results indicated that optimized n-HA/Res/CS composite microspheres could serve as promising multifunctional fillers for osteoporotic bone defect/fracture treatment.展开更多
基金This research was supported by the National Natural Science Foundation of China(81760087/31760292/81860326/81560050)the Department of Science and Technology of Yunnan Province of China(2017FA035/2017FE467(-008)/2018FE001(-137)/2018FE001(-165)/2018FE001(-125)/2018IA048/2019ZF011-2)+1 种基金Major Program of Kunming Science and Technology Innovation Center(2019-1-N-25318000003568)Program for Innovative Research Team(in Science and Technology)in University of Yunnan Province(IRTSTYN).
文摘Vascular grafts must avoid negative inflammatory responses and thrombogenesis to prohibit fibrotic deposition immediately upon implantation and promote the regeneration of small diameter blood vessels(<6 mm inner diameter).Here,polyurethane(PU)elastomers incorporating anti-coagulative and anti-inflammatory Gastrodin were fabricated.The films had inter-connected pores with porosities equal to or greater than 86%and pore sizes ranging from 250 to 400μm.Incorporation of Gastrodin into PU films resulted in desirable mechanical properties,hydrophilicity,swelling ratios and degradation rates without collapse.The released Gastrodin maintained bioactivity over 21 days as assessed by its anti-oxidative capability.The Gastrodin/PU had better anti-coagulation response(less observable BSA,fibrinogen and platelet adhesion/activation and suppressed clotting in whole blood).Red blood cell compatibility,measured by hemolysis,was greatly improved with 2Gastrodin/PU compared to other Gastrodin/PU groups.Notably,Gastrodin/PU upregulated anti-oxidant factors Nrf2 and HO-1 expression in H2O2 treated HUVECs,correlated with decreasing pro-inflammatory cytokines TNF-αand IL-1β in RAW 264.7 cells.Upon implantation in a subcutaneous pocket,PU was encapsulated by an obvious fibrous capsule,concurrent with a large amount of inflammatory cell infiltration,while Gastrodin/PU induced a thinner fibrous capsule,especially 2Gastrodin/PU.Further,enhanced adhesion and proliferation of HUVECs seeded onto films in vitro demonstrated that 2Gastrodin/PU could help cell recruitment,as evidenced by rapid host cell infiltration and substantial blood vessel formation in vivo.These results indicate that 2Gastrodin/PU has the potential to facilitate blood vessel regeneration,thus providing new insight into the development of clinically effective vascular grafts.
基金supported by the National Natural Science Foundation of China(81460173/81860326/81960268)the Department of Science and Technology of Yunnan Province of China(2017FF117(-062)/2018FE001(-137)/2018FE001(-125)/2019ZF011-2).
文摘The development of functional materials for osteoporosis is ultimately required for bone remodeling.However,grafts were accompanied by increasing pro-inflammatory cytokines that impaired bone formation.In this work,nano-hydroxyapatite(n-HA)/resveratrol(Res)/chitosan(CS)composite microspheres were designed to create a beneficial microenvironment and help improve the osteogenesis by local sustained release of Res.Study of in vitro release confirmed the feasibility of n-HA/Res/CS microspheres for controlled Res release.Notably,microspheres had anti-inflammatory activity evidenced by the decreased expression of pro-inflammatory cytokines TNF-α,IL-1βand iNOS in RAW264.7 cells in a dose dependent manner.Further,enhanced adhesion and proliferation of BMSCs seeded onto microspheres demonstrated that composite microspheres were conducive to cell growth.The ability to enhance osteo-differentiation was supported by up-regulation of Runx2,ALP,Col-1 and OCN,and substantial mineralization in osteogenic medium.When implanted into bone defects in the osteoporotic rat femoral condyles,enhanced entochondrostosis and bone regeneration suggested that the n-HA/Res/CS composite microspheres were more favorable for impaired fracture healing.The results indicated that optimized n-HA/Res/CS composite microspheres could serve as promising multifunctional fillers for osteoporotic bone defect/fracture treatment.
