Plasma fibrinogen(F1)and fibronectin(pFN)polymerize to form a fibrin clot that is both a hemostatic and provisional matrix for wound healing.About 90%of plasma F1 has a homodimeric pair ofγchains(γγF1),and 10%has a...Plasma fibrinogen(F1)and fibronectin(pFN)polymerize to form a fibrin clot that is both a hemostatic and provisional matrix for wound healing.About 90%of plasma F1 has a homodimeric pair ofγchains(γγF1),and 10%has a heterodimeric pair ofγand more acidicγ′chains(γγ′F1).We have synthesized a novel fibrin matrix exclusively from a 1:1(molar ratio)complex ofγγ′F1 and pFN in the presence of highly active thrombin and recombinant Factor XIII(rFXIIIa).In this matrix,the fibrin nanofibers were decorated with pFN nanoclusters(termedγγ′F1:pFN fibrin).In contrast,fibrin made from 1:1 mixture ofγγF1 and pFN formed a sporadic distribution of“pFN droplets”(termedγγF1+pFN fibrin).Theγγ′F1:pFN fibrin enhanced the adhesion of primary human umbilical vein endothelium cells(HUVECs)relative to theγγF1+FN fibrin.Three dimensional(3D)culturing showed that theγγ′F1:pFN complex fibrin matrix enhanced the proliferation of both HUVECs and primary human fibroblasts.HUVECs in the 3Dγγ′F1:pFN fibrin exhibited a starkly enhanced vascular morphogenesis while an apoptotic growth profile was observed in theγγF1+pFN fibrin.Relative toγγF1+pFN fibrin,mouse dermal wounds that were sealed byγγ′F1:pFN fibrin exhibited accelerated and enhanced healing.This study suggests that a 3D pFN presentation on a fibrin matrix promotes wound healing.展开更多
Effective therapies are urgently needed to stabilize patients with marginally compressible junctional hemorrhage long enough to get them to the hospital alive.Herein,we report injectable and rapidly expandable cryogel...Effective therapies are urgently needed to stabilize patients with marginally compressible junctional hemorrhage long enough to get them to the hospital alive.Herein,we report injectable and rapidly expandable cryogels consisting of polyacrylamide and thrombin(AT cryogels)created by cryo-polymerization for the efficient management of lethal junctional hemorrhage in swine.The produced cryogels have small pore sizes and highly interconnected porous architecture with robust mechanical strength.The cryogels exhibit rapid shape memory properties and prove to be resilient against fatigue.These cryogels also show high water/blood absorption capacity,fast blood clotting effect,and enhanced adhesion of red blood cells and platelets in vitro.Further,in vivo,hemostatic efficacy tests in a lethal swine junctional hemorrhage model suggest that treatment with AT cryogels,especially AT-2 cryogels,achieves the least blood loss and the highest survival rate(100%)compared to currently employed products such as XStat®and combat gauze.The high hemostatic performance of the cryogels may be attributed to highly interconnected porous architecture with small pore size and the use of thrombin as a pro-coagulant agent.Collectively,injectable and rapidly expandable thrombin-decorated polyacrylamide-based cryogels show significant promise as hemostatic material,offering effective management of marginally compressible junctional hemorrhages in prehospital settings.展开更多
Peripheral arterial disease(PAD)is a progressive atherosclerotic disorder characterized by narrowing and occlusion of arteries supplying the lower extremities.Approximately 200 million people worldwide are affected by...Peripheral arterial disease(PAD)is a progressive atherosclerotic disorder characterized by narrowing and occlusion of arteries supplying the lower extremities.Approximately 200 million people worldwide are affected by PAD.The current standard of operative care is open or endovascular revascularization in which blood flow restoration is the goal.However,many patients are not appropriate candidates for these treatments and are subject to continuous ischemia of their lower limbs.Current research in the therapy of PAD involves developing modalities that induce angiogenesis,but the results of simple cell transplantation or growth factor delivery have been found to be relatively poor mainly due to difficulties in stem cell retention and survival and rapid diffusion and enzymolysis of growth factors following injection of these agents in the affected tissues.Biomaterials,including hydrogels,have the capability to protect stem cells during injection and to support cell survival.Hydrogels can also provide a sustained release of growth factors at the injection site.This review will focus on biomaterial systems currently being investigated as carriers for cell and growth factor delivery,and will also discuss biomaterials as a potential stand-alone method for the treatment of PAD.Finally,the challenges of development and use of biomaterials systems for PAD treatment will be reviewed.展开更多
基金supported by the University of Nebraska Research Initiative 2018–2019(YL and WV)the University of Nebraska-Lincoln start-up(YL)+3 种基金the Nebraska DHHS Stem Cell Grant 2019(YL and WV)the U.S.Army GRANT10824516(WV)the Department of Defense,USA,W81XWH-BAA-11-1(WV)This study was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior–Brasil(CAPES)–Finance Code 88882.434714/2019–01(EPA and LAV)。
文摘Plasma fibrinogen(F1)and fibronectin(pFN)polymerize to form a fibrin clot that is both a hemostatic and provisional matrix for wound healing.About 90%of plasma F1 has a homodimeric pair ofγchains(γγF1),and 10%has a heterodimeric pair ofγand more acidicγ′chains(γγ′F1).We have synthesized a novel fibrin matrix exclusively from a 1:1(molar ratio)complex ofγγ′F1 and pFN in the presence of highly active thrombin and recombinant Factor XIII(rFXIIIa).In this matrix,the fibrin nanofibers were decorated with pFN nanoclusters(termedγγ′F1:pFN fibrin).In contrast,fibrin made from 1:1 mixture ofγγF1 and pFN formed a sporadic distribution of“pFN droplets”(termedγγF1+pFN fibrin).Theγγ′F1:pFN fibrin enhanced the adhesion of primary human umbilical vein endothelium cells(HUVECs)relative to theγγF1+FN fibrin.Three dimensional(3D)culturing showed that theγγ′F1:pFN complex fibrin matrix enhanced the proliferation of both HUVECs and primary human fibroblasts.HUVECs in the 3Dγγ′F1:pFN fibrin exhibited a starkly enhanced vascular morphogenesis while an apoptotic growth profile was observed in theγγF1+pFN fibrin.Relative toγγF1+pFN fibrin,mouse dermal wounds that were sealed byγγ′F1:pFN fibrin exhibited accelerated and enhanced healing.This study suggests that a 3D pFN presentation on a fibrin matrix promotes wound healing.
基金supported by startup funds from the University of Nebraska Medical Center(UNMC)and Congressionally Directed Medical Research Program(CDMRP)/Peer Reviewed Medical Research Program(PRMRP)FY19 W81XWH2010207 to J.X.M.A.C.We thank the Proteomics&Metabolomics Facility(RRID:SCR_021314),Nebraska Center for Biotechnology at the University of Nebraska-Lincoln for the mass spectrometry analysis.The facility and instrumentation are supported by the Nebraska Research Initiative.
文摘Effective therapies are urgently needed to stabilize patients with marginally compressible junctional hemorrhage long enough to get them to the hospital alive.Herein,we report injectable and rapidly expandable cryogels consisting of polyacrylamide and thrombin(AT cryogels)created by cryo-polymerization for the efficient management of lethal junctional hemorrhage in swine.The produced cryogels have small pore sizes and highly interconnected porous architecture with robust mechanical strength.The cryogels exhibit rapid shape memory properties and prove to be resilient against fatigue.These cryogels also show high water/blood absorption capacity,fast blood clotting effect,and enhanced adhesion of red blood cells and platelets in vitro.Further,in vivo,hemostatic efficacy tests in a lethal swine junctional hemorrhage model suggest that treatment with AT cryogels,especially AT-2 cryogels,achieves the least blood loss and the highest survival rate(100%)compared to currently employed products such as XStat®and combat gauze.The high hemostatic performance of the cryogels may be attributed to highly interconnected porous architecture with small pore size and the use of thrombin as a pro-coagulant agent.Collectively,injectable and rapidly expandable thrombin-decorated polyacrylamide-based cryogels show significant promise as hemostatic material,offering effective management of marginally compressible junctional hemorrhages in prehospital settings.
基金supported by funds from University of Nebraska Medical Center,American Heart Association Career Development Award(18CDA34110314)Nebraska Stem Cell Research Project(NE LB606)and R01AG062198+1 种基金support by a grant from the National Institute of General Medical Sciences,1U54GM115458the UNMC Center for Heart and Vascular Research。
文摘Peripheral arterial disease(PAD)is a progressive atherosclerotic disorder characterized by narrowing and occlusion of arteries supplying the lower extremities.Approximately 200 million people worldwide are affected by PAD.The current standard of operative care is open or endovascular revascularization in which blood flow restoration is the goal.However,many patients are not appropriate candidates for these treatments and are subject to continuous ischemia of their lower limbs.Current research in the therapy of PAD involves developing modalities that induce angiogenesis,but the results of simple cell transplantation or growth factor delivery have been found to be relatively poor mainly due to difficulties in stem cell retention and survival and rapid diffusion and enzymolysis of growth factors following injection of these agents in the affected tissues.Biomaterials,including hydrogels,have the capability to protect stem cells during injection and to support cell survival.Hydrogels can also provide a sustained release of growth factors at the injection site.This review will focus on biomaterial systems currently being investigated as carriers for cell and growth factor delivery,and will also discuss biomaterials as a potential stand-alone method for the treatment of PAD.Finally,the challenges of development and use of biomaterials systems for PAD treatment will be reviewed.
