Cartilage defect repair and osteoarthritis treatments remain clinical challenges.Microfracture is a commonly used surgical procedure for the treatment of cartilage defects but often leads to fibrocartilage repair.The ...Cartilage defect repair and osteoarthritis treatments remain clinical challenges.Microfracture is a commonly used surgical procedure for the treatment of cartilage defects but often leads to fibrocartilage repair.The aim of this study is to compare the effects of 5 bone morphogenetic proteins(BMPs)on chondrogenic differentiation of human bone marrow mesenchymal stem cells,as well as to investigate the use of the heparin/poly(ethylene arginine aspartate diglyceride(PEAD)coacervate sustained release system to deliver these BMPs for microfracture-mediated cartilage repair.Our results indicate that all 5 human BMPs significantly enhance the chondrogenic differentiation of human bone marrow mesenchymal stem cells(hBMMSCs)with BMPs 2,4 and 9 being more potent than BMP6 or BMP7,as revealed by Alcian blue,SO staining,and immunohistochemistry of COL2.Coacervate-BMPs are biocompatible for both hBMMSCs and rat muscle-derived stem cells(MDSCs)and promote their proliferation.In vivo,sustained release of human BMPs 2,4,6,7,9 with heparin/PEAD coacervate significantly enhances microfracture-mediated cartilage repair in a rat osteochondral defect model,as demon-strated by ICRS macroscopic score,Seller’s histology score,and COL2 staining.These effects are mediated by increasing SOX9 expression in the regenerated cartilage.In conclusion,BMPs 2,4,9 are the most potent BMPS to promote chondrogenic differentiation,while all BMPs enhanced microfracture-mediated cartilage repair when delivered with heparin/PEAD coacervate without a significant difference between the different BMPs.展开更多
Controlled delivery of proteins and other biologics is a growing medium of therapy for diseases previously untreatable.Here we report a self-assembling,tunable vesicle for the controlled delivery of growth factors and...Controlled delivery of proteins and other biologics is a growing medium of therapy for diseases previously untreatable.Here we report a self-assembling,tunable vesicle for the controlled delivery of growth factors and cytokines.Coacervate made of heparin and a biocompatible polycation,PEAD,forms the core of the vesicle;lipids form the membrane of the vesicle.We call this vesicle lipocoacervate(LipCo),which has a high affinity for growth factors and cytokines due to heparin.LipCo is a tunable protein delivery vehicle.The vesicle size is controlled through polymer and salt concentrations.Membrane functionalization enables potential for targeting capabilities with long-term storage through lyophilization.Importantly,the controlled delivery of therapeutics also avoids high toxicity to treated cells in vitro.Here we report on these key principles of LipCo assembly and design.展开更多
基金supported by a Philanthropy gift from the Musculo-skeletal Regeneration Partnership Fund by Mary Sue and Michael Shannon and NIH RO1(R01NR016436)to Dr.Yadong Wang.We Thank Dr.Ehrhart’s lab for providing surgery suite and help with animal pro-tocol.
文摘Cartilage defect repair and osteoarthritis treatments remain clinical challenges.Microfracture is a commonly used surgical procedure for the treatment of cartilage defects but often leads to fibrocartilage repair.The aim of this study is to compare the effects of 5 bone morphogenetic proteins(BMPs)on chondrogenic differentiation of human bone marrow mesenchymal stem cells,as well as to investigate the use of the heparin/poly(ethylene arginine aspartate diglyceride(PEAD)coacervate sustained release system to deliver these BMPs for microfracture-mediated cartilage repair.Our results indicate that all 5 human BMPs significantly enhance the chondrogenic differentiation of human bone marrow mesenchymal stem cells(hBMMSCs)with BMPs 2,4 and 9 being more potent than BMP6 or BMP7,as revealed by Alcian blue,SO staining,and immunohistochemistry of COL2.Coacervate-BMPs are biocompatible for both hBMMSCs and rat muscle-derived stem cells(MDSCs)and promote their proliferation.In vivo,sustained release of human BMPs 2,4,6,7,9 with heparin/PEAD coacervate significantly enhances microfracture-mediated cartilage repair in a rat osteochondral defect model,as demon-strated by ICRS macroscopic score,Seller’s histology score,and COL2 staining.These effects are mediated by increasing SOX9 expression in the regenerated cartilage.In conclusion,BMPs 2,4,9 are the most potent BMPS to promote chondrogenic differentiation,while all BMPs enhanced microfracture-mediated cartilage repair when delivered with heparin/PEAD coacervate without a significant difference between the different BMPs.
文摘Controlled delivery of proteins and other biologics is a growing medium of therapy for diseases previously untreatable.Here we report a self-assembling,tunable vesicle for the controlled delivery of growth factors and cytokines.Coacervate made of heparin and a biocompatible polycation,PEAD,forms the core of the vesicle;lipids form the membrane of the vesicle.We call this vesicle lipocoacervate(LipCo),which has a high affinity for growth factors and cytokines due to heparin.LipCo is a tunable protein delivery vehicle.The vesicle size is controlled through polymer and salt concentrations.Membrane functionalization enables potential for targeting capabilities with long-term storage through lyophilization.Importantly,the controlled delivery of therapeutics also avoids high toxicity to treated cells in vitro.Here we report on these key principles of LipCo assembly and design.
