Stable integration of hydrogel implants with host tissues is of critical importance to cartilage tissue engineering.Designing and fabricating hydrogels with high adhesive strength,stability and regeneration potential ...Stable integration of hydrogel implants with host tissues is of critical importance to cartilage tissue engineering.Designing and fabricating hydrogels with high adhesive strength,stability and regeneration potential are major challenges to be overcome.This study fabricated injectable adhesive hyaluronic acid(HA)hydrogel modified by aldehyde groups and methacrylate(AHAMA)on the polysaccharide backbone with multiple anchoring mechanisms(amide bond through the dynamic Schiff base reaction,hydrogen bond and physical interpenetration).AHAMA hydrogel exhibited significantly improved durability and stability within a humid environment(at least 7 days),together with higher adhesive strength(43 KPa to skin and 52 KPa to glass),as compared to commercial fibrin glue(nearly 10 KPa)and HAMA hydrogel(nearly 20 KPa).The results showed that AHAMA hydrogel was biocompatible and could be easily and rapidly prepared in situ.In vitro cell culture experiments showed that AHAMA hydrogel could enhance proliferation(1.2-folds after 3 days)and migration(1.5-folds after 12 h)of bone marrow stem cells(BMSCs),as compared to cells cultured in a culture dish.Furthermore,in a rat osteochondral defect model,implanted AHAMA hydrogel significantly promoted integration between neo-cartilage and host tissues,and significantly improved cartilage regeneration(modified O’Driscoll histological scores of 16.0±4.1 and 18.3±4.6 after 4 and 12-weeks of post-implantation in AHAMA groups respectively,12.0±2.7 and 12.2±2.8 respectively in HAMA groups,9.8±2.4 and 11.5±2.1 respectively in untreated groups).Hence,AHAMA hydrogel is a promising adhesive biomaterial for clinical cartilage regeneration and other biomedical applications.展开更多
Mesenchymal stem cells(MSCs) are important cell sources in cartilage tissue development and homeostasis,and multiple strategies have been developed to improve MSCs chondrogenic differentiation with an aim of promoting...Mesenchymal stem cells(MSCs) are important cell sources in cartilage tissue development and homeostasis,and multiple strategies have been developed to improve MSCs chondrogenic differentiation with an aim of promoting cartilage regeneration.Here we report the effects of combining nanosecond pulsed electric fields(ns PEFs) followed by treatment with ghrelin(a hormone that stimulates release of growth hormone) to regulate chondrogenesis of MSCs.ns PEFs and ghrelin were observed to separately enhance the chondrogenesis of MSCs,and the effects were significantly enhanced when the bioelectric stimulation and hormone were combined,which in turn improved osteochondral tissue repair of these cells within Sprague Dawley rats.We further found that ns PEFs can prime MSCs to be more receptive to subsequent stimuli of differentiation by upregulated Oct4/Nanog and activated JNK signaling pathway.Ghrelin initiated chondrogenic differentiation by activation of ERK1/2 signaling pathway,and RNA-seq results indicated 243 genes were regulated,and JAK-STAT signaling pathway was involved.Interestingly,the sequential order of applying these two stimuli is critical,with ns PEFs pretreatment followed by ghrelin enhanced chondrogenesis of MSCs in vitro and subsequent cartilage regeneration in vivo,but not vice versa.This synergistic prochondrogenic effects provide us new insights and strategies for future cell-based therapies.展开更多
With the interdisciplinary convergence of biology,medicine and materials science,both research and clinical translation of biomaterials are progressing at a rapid pace.However,there is still a huge gap between applied...With the interdisciplinary convergence of biology,medicine and materials science,both research and clinical translation of biomaterials are progressing at a rapid pace.However,there is still a huge gap between applied basic research on biomaterials and their translational products-medical devices,where two significantly different perspectives and mindsets often work independently and non-synergistically,which in turn significantly increases financial costs and research effort.Although this gap is well-known and often criticized in the biopharmaceutical industry,it is gradually widening.In this article,we critically examine the developmental pipeline of biodegradable biomaterials and biomaterial-based medical device products.Then based on clinical needs,market analysis,and relevant regulations,some ideas are proposed to integrate the two different mindsets to guide applied basic research and translation of biomaterial-based products,from the material and technical perspectives.Cartilage repair substitutes are discussed here as an example.Hopefully,this will lay a strong foundation for biomaterial research and clinical translation,while reducing the amount of extra research effort and funding required due to the dissonance between innovative basic research and commercialization pipeline.展开更多
Along with the role transformation of biomaterials from bioinert substitute to regenerative inducer, the biological effect and mechanism of material-organism interaction become more important. Since most of animal tes...Along with the role transformation of biomaterials from bioinert substitute to regenerative inducer, the biological effect and mechanism of material-organism interaction become more important. Since most of animal tests and cellular experiments stay on the phenomenon description instead of mechanism interpretation, the development of proteomics technologies provides a golden opportunity to uncover the molecular interaction mechanism between biomaterial-organism on whole scale. This review summarizes current application of proteomics in biological effect and mechanism study of biomaterials, and discusses the development and challenges for future studies.展开更多
基金This work was supported by the National Natural Science Foundation of China grant(81772334)Peking University Medicine Seed Fund for Interdisciplinary Research(BMU2018ME001).
文摘Stable integration of hydrogel implants with host tissues is of critical importance to cartilage tissue engineering.Designing and fabricating hydrogels with high adhesive strength,stability and regeneration potential are major challenges to be overcome.This study fabricated injectable adhesive hyaluronic acid(HA)hydrogel modified by aldehyde groups and methacrylate(AHAMA)on the polysaccharide backbone with multiple anchoring mechanisms(amide bond through the dynamic Schiff base reaction,hydrogen bond and physical interpenetration).AHAMA hydrogel exhibited significantly improved durability and stability within a humid environment(at least 7 days),together with higher adhesive strength(43 KPa to skin and 52 KPa to glass),as compared to commercial fibrin glue(nearly 10 KPa)and HAMA hydrogel(nearly 20 KPa).The results showed that AHAMA hydrogel was biocompatible and could be easily and rapidly prepared in situ.In vitro cell culture experiments showed that AHAMA hydrogel could enhance proliferation(1.2-folds after 3 days)and migration(1.5-folds after 12 h)of bone marrow stem cells(BMSCs),as compared to cells cultured in a culture dish.Furthermore,in a rat osteochondral defect model,implanted AHAMA hydrogel significantly promoted integration between neo-cartilage and host tissues,and significantly improved cartilage regeneration(modified O’Driscoll histological scores of 16.0±4.1 and 18.3±4.6 after 4 and 12-weeks of post-implantation in AHAMA groups respectively,12.0±2.7 and 12.2±2.8 respectively in HAMA groups,9.8±2.4 and 11.5±2.1 respectively in untreated groups).Hence,AHAMA hydrogel is a promising adhesive biomaterial for clinical cartilage regeneration and other biomedical applications.
基金supported by the National Key Research and Development Program of China (2019YFA0111900)the National Natural Science Foundation of China (81772334)。
文摘Mesenchymal stem cells(MSCs) are important cell sources in cartilage tissue development and homeostasis,and multiple strategies have been developed to improve MSCs chondrogenic differentiation with an aim of promoting cartilage regeneration.Here we report the effects of combining nanosecond pulsed electric fields(ns PEFs) followed by treatment with ghrelin(a hormone that stimulates release of growth hormone) to regulate chondrogenesis of MSCs.ns PEFs and ghrelin were observed to separately enhance the chondrogenesis of MSCs,and the effects were significantly enhanced when the bioelectric stimulation and hormone were combined,which in turn improved osteochondral tissue repair of these cells within Sprague Dawley rats.We further found that ns PEFs can prime MSCs to be more receptive to subsequent stimuli of differentiation by upregulated Oct4/Nanog and activated JNK signaling pathway.Ghrelin initiated chondrogenic differentiation by activation of ERK1/2 signaling pathway,and RNA-seq results indicated 243 genes were regulated,and JAK-STAT signaling pathway was involved.Interestingly,the sequential order of applying these two stimuli is critical,with ns PEFs pretreatment followed by ghrelin enhanced chondrogenesis of MSCs in vitro and subsequent cartilage regeneration in vivo,but not vice versa.This synergistic prochondrogenic effects provide us new insights and strategies for future cell-based therapies.
基金This work was supported by the National Natural Science Foundation of China grant(81772334).
文摘With the interdisciplinary convergence of biology,medicine and materials science,both research and clinical translation of biomaterials are progressing at a rapid pace.However,there is still a huge gap between applied basic research on biomaterials and their translational products-medical devices,where two significantly different perspectives and mindsets often work independently and non-synergistically,which in turn significantly increases financial costs and research effort.Although this gap is well-known and often criticized in the biopharmaceutical industry,it is gradually widening.In this article,we critically examine the developmental pipeline of biodegradable biomaterials and biomaterial-based medical device products.Then based on clinical needs,market analysis,and relevant regulations,some ideas are proposed to integrate the two different mindsets to guide applied basic research and translation of biomaterial-based products,from the material and technical perspectives.Cartilage repair substitutes are discussed here as an example.Hopefully,this will lay a strong foundation for biomaterial research and clinical translation,while reducing the amount of extra research effort and funding required due to the dissonance between innovative basic research and commercialization pipeline.
基金support of Natural Science Foundation of Guangdong Province, China (Nos. 2016A030310245 and 2016A030310244)China Postdoctoral Science Foundation (No. 2016M591017)Key Projects in the National Science &Technology Pillar program during the thirteenth Five-year Plan Period (No. 2016YFC1102800)
文摘Along with the role transformation of biomaterials from bioinert substitute to regenerative inducer, the biological effect and mechanism of material-organism interaction become more important. Since most of animal tests and cellular experiments stay on the phenomenon description instead of mechanism interpretation, the development of proteomics technologies provides a golden opportunity to uncover the molecular interaction mechanism between biomaterial-organism on whole scale. This review summarizes current application of proteomics in biological effect and mechanism study of biomaterials, and discusses the development and challenges for future studies.
