[ Objective] To prepare recombinant type 1 pilus vaccine of avian Escherichia coil and to detect its immunogenicity in chickens. [Meth- od] The type 1 pilus was respectively isolated from the recombinant bacteria CZYR...[ Objective] To prepare recombinant type 1 pilus vaccine of avian Escherichia coil and to detect its immunogenicity in chickens. [Meth- od] The type 1 pilus was respectively isolated from the recombinant bacteria CZYR10 strain and wild avian Eschedchia co/i YR（ O18 ） strain and used to prepare oil-emulsified vaccine. The immunogenicity of the developed vaccine was detected in chickens using the challenge test. [ Result] The recombinant type 1 pilus protein had immunoprotective efficacy. The recombinant type 1 pilus protein had weaker protective efficacy than the isolated type 1 pilus protein, but the difference was not significant. [ Conclusion] The study provides a reference for immunization and control of chicken colibacillosis.展开更多
BACKGROUND:The study aimed to compare the therapeutic effect of recombinant tissue plasminogen activator(rt-PA) on the onset of acute cerebral infarction(ACI) at different time points of the first 6 hours.METHODS:A re...BACKGROUND:The study aimed to compare the therapeutic effect of recombinant tissue plasminogen activator(rt-PA) on the onset of acute cerebral infarction(ACI) at different time points of the first 6 hours.METHODS:A retrospective analysis was conducted in 74 patients who received rt-PA thrombolysis treatment within 4.5 hours after ACI and another 15 patients who received rt-PA thrombolysis treatment between 4.5-6 hours after ACI.RESULTS:National Institute of Health Stroke Scale(NIHSS) scores were statistically decreased in both groups(P>0.05) at 24 hours and 7 days after ACI.There was no significant difference in modified ranking scores and mortality at 90 days after the treatment between the two groups(P>0.05).CONCLUSIONS:The therapeutic effect and mortality of rt-PA treatment in patients with ACI between 4.5-6 hours after the onset of the disease were similar to those in patients who received rtPA within 4.5 hours after the onset of this disease.Therefore,intravenous thrombolytic therapy for ACI within 4.5-6 hours after ACI was effective and safe.展开更多
Mid-facial depression is a key sign of facial aging,primarily caused by the loss of collagen leading to depletion of the extracellular matrix(ECM).However,the existing fillers for soft tissue augmentation have shown c...Mid-facial depression is a key sign of facial aging,primarily caused by the loss of collagen leading to depletion of the extracellular matrix(ECM).However,the existing fillers for soft tissue augmentation have shown certain limitations in repairing mid-facial depression.Therefore,we herein report the development of a novel recombinant humanized type Ⅲ collagen gel(C3Gel)through rational design and modification of a commercially available recombinant typeⅢhumanized collagen lyophilized fiber product.Both biological activity and tissue repair mechanisms of C3Gel were systematically evaluated in vitro and in vivo.C3Gel formed a dense fibrous structure around cells,significantly improving the ECM environment and providing strong support for cells,thereby promoting cell adhesion,migration,and proliferation.After injection of C3Gel into the dorsal region of rats,we observed a significant increase in the expression of type I collagen and elastin that improved tissue mechanical properties and elasticity.High-throughput RNA sequencing analysis revealed that C3Gel activated the integrin signaling pathway to improve binding between cells and ECM,resulting in the increased expression of downstream genes by activating the PI3KAkt pathway which promoted the production of ECM components,such as collagen and laminin.At the same time,the expression of matrix metalloproteinases was inhibited to maintain ECM stability.Moreover,C3Gel is not carcinogenic in mice.Therefore,C3Gel demonstrates excellent biocompatibility and significant tissue repair ability,offering a safe,efficient,and long-term stable solution for mid-facial soft tissue augmentation,while providing new insights for other applications in regenerative medicine.展开更多
Scar formation can be effectively prevented when the proportion of collagen type Ⅰ(Col Ⅰ)/type Ⅲ(Col Ⅲ)is reduced.Unlike Col Ⅲ,recombinant human collagen type Ⅲ chain(RHC Ⅲ chain)does not possess a triple helic...Scar formation can be effectively prevented when the proportion of collagen type Ⅰ(Col Ⅰ)/type Ⅲ(Col Ⅲ)is reduced.Unlike Col Ⅲ,recombinant human collagen type Ⅲ chain(RHC Ⅲ chain)does not possess a triple helical structure.This study aimed to elucidate the capacity of fibroblasts to uptake RHC Ⅲ chain,reduce the Col Ⅰ/Col Ⅲ ratio and determine its effects on wound healing and scar.RHC Ⅲ chain demonstrates qualified cell compatibility.In cell experiments,immunofluorescence and western blot(WB)analyses revealed an increase in the polyhistidine tag level,indicating that RHC Ⅲ chain in internalized by these cells.Transmission electron microscopy showed increased intracellular phagocytic activity,indicating that RHC Ⅲ chain enters fibroblasts by endocytosis.The immunofluorescence and WB showed that Col Ⅲ synthesis enhanced,and Col Ⅰ/Col Ⅲ ratio reduced.However,the polyhistidine tag disappeared with time,indicating that RHC Ⅲ chain degraded within cells and then synthesized into Col Ⅲ.The content of newly synthesized Col Ⅲ increases,but real-time fluorescence quantitative showed a decrease in Col Ⅲ related gene content suggests the formation of negative feedback.However,due to the sufficient raw materials,the amount of Col Ⅲ synthesis is still increasing,leading to the reduction of the ratio of type Ⅰ collagen/type Ⅲ collagen,which beneficial to wound healing and reduce scar hyperplasia.In animal experiments,the SD rat full-thickness skin defect model of wound suggests that RHC Ⅲ chain also takes effect through endocytosis and ultimately promotes wound healing.The rabbit ear scar model suggests that RHC Ⅲ chain inhibits scar proliferation by reducing the ratio of Col Ⅰ/Col Ⅲ.In summary,RHC Ⅲ chain was endocytosed by fibroblasts to promote native Col Ⅲ synthesis,as well as promote wound healing and reduce scar hyperplasia.展开更多
Effective treatment of rheumatoid arthritis can be mediated by native chicken type II collagen(n CCII), recombinant peptide containing n CCII tolerogenic epitopes(CTEs), or a therapeutic DNA vaccine encoding the full-...Effective treatment of rheumatoid arthritis can be mediated by native chicken type II collagen(n CCII), recombinant peptide containing n CCII tolerogenic epitopes(CTEs), or a therapeutic DNA vaccine encoding the full-length CCOL2 A1 c DNA. As recombinant CCII(r CCII) might avoid potential pathogenic virus contamination during n CCII preparation or chromosomal integration and oncogene activation associated with DNA vaccines, here we evaluated the importance of propeptide and telopeptide domains on r CCII triple helix molecular assembly. We constructed p C-and p N-procollagen(without N-or Cpropeptides, respectively) as well as CTEs located in the triple helical domain lacking both propeptides and telopeptides, and expressed these in yeast Pichia pastoris host strain GS115(his4, Mut+) simultaneously with recombinant chicken prolyl-4-hydroxylase α and β subunits. Both p C-and p N-procollagen monomers accumulated inside P. pastoris cells, whereas CTE was assembled into homotrimers with stable conformation and secreted into the supernatants, suggesting that the large molecular weight p C-or p N-procollagens were retained within the endoplasmic reticulum whereas the smaller CTEs proceeded through the secretory pathway. Furthermore, resulting recombinant chicken type II collagen p Cα1(II) can induce collagen-induced arthritis(CIA) rat model, which seems to be as effective as the current standard n CCII. Notably, protease digestion assays showed that r CCII could assemble in the absence of C-and N-propeptides or telopeptides. These findings provide new insights into the minimal structural requirements for r CCII expression and folding.展开更多
Collagen, recognized as the primary structural component of human skin, is essential for preserving dermal integrity and function. Its progressive depletion has been closely associated with structural deterioration of...Collagen, recognized as the primary structural component of human skin, is essential for preserving dermal integrity and function. Its progressive depletion has been closely associated with structural deterioration of the dermis and the visible signs of skin aging. Among current therapeutic strategies, the injection of exogenous collagen has been established as an effective method for alleviating aging-related skin changes. In the present study, a comprehensive evaluation was conducted to assess the injectability, cellular interactions, and photoaging repair efficacy of recombinant human collagen type III(RHC). The RHC solution was found to demonstrate favorable injectability and support the adhesion and chemotactic behavior of L929 cells, while also upregulating the expression of type I and type III collagen. In co-culture systems with lipopolysaccharide-stimulated macrophages, RHC treatment suppressed macrophage proliferation and reduced the production of proinflammatory cytokines, suggesting notable immunomodulatory properties. Upon intradermal injection of RHC into photoaged rat skin, an increased density of dermal collagen fibers was observed, accompanied by a more organized and uniform fiber arrangement. Additionally, hydroxyproline content and the expressions of collagen I and III were markedly elevated in the RHC group compared with the control and hyaluronic acid groups. Collectively, these findings suggest that RHC holds considerable promise as a therapeutic agent for both medical and cosmetic purposes targeting the restoration and maintenance of youthful skin characteristics.展开更多
Anti-inflammation and anti-coagulation are the primary requirements for cardiovascular stents and also the widely accepted trajectory for multi-functional modification.In this work,we proposed an extracellular matrix(...Anti-inflammation and anti-coagulation are the primary requirements for cardiovascular stents and also the widely accepted trajectory for multi-functional modification.In this work,we proposed an extracellular matrix(ECM)-mimetic coating for cardiovascular stents with the amplified functionalization of recombinant humanized collagen type III(rhCOL III),where the biomimetics were driven by structure mimicry and component/function mimicry.Briefly,the structure-mimic was constructed by the formation of a nanofiber(NF)structure via the polymerization of polysiloxane with a further introduction of amine groups as the nanofibrous layer.The fiber network could function as a three-dimensional reservoir to support the amplified immobilization of rhCoL III.The rhCOL III was tailored for anti-coagulant,anti-inflammatory and endothelialization promotion properties,which endows the ECM-mimetic coating with desired surface functionalities.Stent implantation in the abdominal aorta of rabbits was conducted to validate the in vivo re-endothelialization of the ECM-mimetic coating.The mild inflammatory responses,anti-thrombotic property,promotion of endothelialization and suppression of excessive neointimal hyperplasia confirmed that the ECM-mimetic coating provided a promising approach for the modification of vascular implants.展开更多
Bioprosthetic heart valve(BHV)replacement has been the predo-minant treatment for severe heart valve diseases over decades.Most clinically available BHVs are crosslinked by glutaraldehyde(GLUT),while the high toxicity...Bioprosthetic heart valve(BHV)replacement has been the predo-minant treatment for severe heart valve diseases over decades.Most clinically available BHVs are crosslinked by glutaraldehyde(GLUT),while the high toxicity of residual GLUT could initiate calcification,severe thrombosis,and delayed endothelializa-tion.Here,we construed a mechanically integrating robust hydrogel-tissue hybrid to improve the performance of BHVs.In particular,recombinant humanized coilagen type Ⅲ(rhCOLⅢ),which was precisely customized with anti-coagulant and pro-endothelialization bioactivity,was first incorporated into the polyvinyl alcohol(PVA)-based hydrogel via hydrogen bond interactions.Then,tannic acid was introduced to enhance the mechanicalperfo of PVA-based hvdrogel and interfacial bonding between the hydrogel layer and bio-derived tissue due to the strong affinity for a wide range of substrates.In vitro and in vivo experimental results confirmed that the GLUT-crosslinked BHVs modified by the robust PVA-based hydrogel embedded rhCOLII and TA possessed long-term anti-coagulant,accelerated endothelialization,mild inflammatory response and anti-calcification properties.Therefore,our mechanically integrating robust hydrogel-tissue hybrid strategy showed the potential to enhance the service function and prolong the service life of the BHVs after implantation.展开更多
Background Spinal cord injury （SCI） is a serious neurological injury that often leads to permanent disabilities for the victims. The aim of this study was to determine the effects of glial-derived neurotrophic fact...Background Spinal cord injury （SCI） is a serious neurological injury that often leads to permanent disabilities for the victims. The aim of this study was to determine the effects of glial-derived neurotrophic factor （GDNF） mediated by recombinant adeno-associated virus type 2 （rAAV2） alone or in combination with early rehabilitation training on SCI. Methods SCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats. Then besides the sham operation group, the SCI rats were randomly divided into four groups： natural healing group, gene therapy group, rehabilitation training group, and combination therapy group （gene therapy in combination with rehabilitation training）. Motor dysfunction, protein expression of GDNF, edema formation, and cell injury were examined 7, 14, and 21 days after trauma. Results The topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF, especially after the 14th day, and could protect the motor neuron cells. Early rehabilitative treatment resulted in significantly improved motor function, reduced edema formation, and protected the cells from injury, especially after the 7th and 14th days, and increased the GDNF expression in the damaged area, which was most evident after Day 14. The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days. Conclusion These observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.展开更多
The objective of regenerative wound healing dressings is to accelerate skin tissue regeneration and restore normal physiological function at wound sites.Achieving this goal requires biomaterials capable of repairing d...The objective of regenerative wound healing dressings is to accelerate skin tissue regeneration and restore normal physiological function at wound sites.Achieving this goal requires biomaterials capable of repairing distinct phases of wound healing in a way that balanc es material function,degradation,safety,and tissue growth.In this study,we introduced a novel dual-stage wound dressing system comprising methacrylic anhydride-modified recombinant humanized type Ⅲ collagen(rhCol Ⅲ-MA) and methacrylic anhydride-modified dopamine(DMA)(RMDM),which was synthesized through free radical polymerization and π-π stacking.Within this system,RMDM was formulated into two forms with identic al compositions:hydrogel and sponge,tailored for application across various stages of wound repair.These materials displayed favorable hemocompatibility,biocompatibility,antioxidant properties,and angiogenic potential in vitro.Moreover,the in vivo experiments also demonstrated that sponges could rapidly stop the bleeding of wounds in mouse tail amputation and liver incision models.Notably,the sponge/gel(S/G) system accelerated wound healing compared to individual sponge and gel treatments in a rat full-thickness skin wound model,underscoring the synergistic benefits of combining sponge and gel materials for wound repair at different stages.Therefo re,this research provides valuable insights into designing advanced biomaterials that can be tailored to specific stages of wound healing,which may have significant potential for biomedical applications.展开更多
基金funded by the Natural Science Foundation of Jiangsu Province ( BK2008059)
文摘[ Objective] To prepare recombinant type 1 pilus vaccine of avian Escherichia coil and to detect its immunogenicity in chickens. [Meth- od] The type 1 pilus was respectively isolated from the recombinant bacteria CZYR10 strain and wild avian Eschedchia co/i YR（ O18 ） strain and used to prepare oil-emulsified vaccine. The immunogenicity of the developed vaccine was detected in chickens using the challenge test. [ Result] The recombinant type 1 pilus protein had immunoprotective efficacy. The recombinant type 1 pilus protein had weaker protective efficacy than the isolated type 1 pilus protein, but the difference was not significant. [ Conclusion] The study provides a reference for immunization and control of chicken colibacillosis.
基金supported by a grant from Shanghai Municipal Health Bureau(GWDTR201219)
文摘BACKGROUND:The study aimed to compare the therapeutic effect of recombinant tissue plasminogen activator(rt-PA) on the onset of acute cerebral infarction(ACI) at different time points of the first 6 hours.METHODS:A retrospective analysis was conducted in 74 patients who received rt-PA thrombolysis treatment within 4.5 hours after ACI and another 15 patients who received rt-PA thrombolysis treatment between 4.5-6 hours after ACI.RESULTS:National Institute of Health Stroke Scale(NIHSS) scores were statistically decreased in both groups(P>0.05) at 24 hours and 7 days after ACI.There was no significant difference in modified ranking scores and mortality at 90 days after the treatment between the two groups(P>0.05).CONCLUSIONS:The therapeutic effect and mortality of rt-PA treatment in patients with ACI between 4.5-6 hours after the onset of the disease were similar to those in patients who received rtPA within 4.5 hours after the onset of this disease.Therefore,intravenous thrombolytic therapy for ACI within 4.5-6 hours after ACI was effective and safe.
基金financially supported by the Taiyuan’s“Open bidding for selecting the best candidates”Program(2024TYJB0149 to Y.Z.)Beijing Natural Science Foundation(JQ24056 to Y.Z.).
文摘Mid-facial depression is a key sign of facial aging,primarily caused by the loss of collagen leading to depletion of the extracellular matrix(ECM).However,the existing fillers for soft tissue augmentation have shown certain limitations in repairing mid-facial depression.Therefore,we herein report the development of a novel recombinant humanized type Ⅲ collagen gel(C3Gel)through rational design and modification of a commercially available recombinant typeⅢhumanized collagen lyophilized fiber product.Both biological activity and tissue repair mechanisms of C3Gel were systematically evaluated in vitro and in vivo.C3Gel formed a dense fibrous structure around cells,significantly improving the ECM environment and providing strong support for cells,thereby promoting cell adhesion,migration,and proliferation.After injection of C3Gel into the dorsal region of rats,we observed a significant increase in the expression of type I collagen and elastin that improved tissue mechanical properties and elasticity.High-throughput RNA sequencing analysis revealed that C3Gel activated the integrin signaling pathway to improve binding between cells and ECM,resulting in the increased expression of downstream genes by activating the PI3KAkt pathway which promoted the production of ECM components,such as collagen and laminin.At the same time,the expression of matrix metalloproteinases was inhibited to maintain ECM stability.Moreover,C3Gel is not carcinogenic in mice.Therefore,C3Gel demonstrates excellent biocompatibility and significant tissue repair ability,offering a safe,efficient,and long-term stable solution for mid-facial soft tissue augmentation,while providing new insights for other applications in regenerative medicine.
基金supported by the Science and Technology Action Innovation Plan of Shanghai[23QB1401000,24S11901800]the Young Innovative Talents Project of Zhejiang Health Science and Technology Plan[2022RC237]+3 种基金Medical and Health Science and Technology Project of Hangzhou[B20200432]Special Policy for Shanghai University Science and Technology Park-Science and Technology Innovation Special Fund[2021-HSD-8-1-004]Epidemic-related projects of the Special Policy for Science and Technology Park Around Shanghai UniversitySpecial Fund for Promoting High-Quality Development in Shanghai-Key Fields of Industrial Strategy Technology Research-Biomedical Special Topic[SY2022008].
文摘Scar formation can be effectively prevented when the proportion of collagen type Ⅰ(Col Ⅰ)/type Ⅲ(Col Ⅲ)is reduced.Unlike Col Ⅲ,recombinant human collagen type Ⅲ chain(RHC Ⅲ chain)does not possess a triple helical structure.This study aimed to elucidate the capacity of fibroblasts to uptake RHC Ⅲ chain,reduce the Col Ⅰ/Col Ⅲ ratio and determine its effects on wound healing and scar.RHC Ⅲ chain demonstrates qualified cell compatibility.In cell experiments,immunofluorescence and western blot(WB)analyses revealed an increase in the polyhistidine tag level,indicating that RHC Ⅲ chain in internalized by these cells.Transmission electron microscopy showed increased intracellular phagocytic activity,indicating that RHC Ⅲ chain enters fibroblasts by endocytosis.The immunofluorescence and WB showed that Col Ⅲ synthesis enhanced,and Col Ⅰ/Col Ⅲ ratio reduced.However,the polyhistidine tag disappeared with time,indicating that RHC Ⅲ chain degraded within cells and then synthesized into Col Ⅲ.The content of newly synthesized Col Ⅲ increases,but real-time fluorescence quantitative showed a decrease in Col Ⅲ related gene content suggests the formation of negative feedback.However,due to the sufficient raw materials,the amount of Col Ⅲ synthesis is still increasing,leading to the reduction of the ratio of type Ⅰ collagen/type Ⅲ collagen,which beneficial to wound healing and reduce scar hyperplasia.In animal experiments,the SD rat full-thickness skin defect model of wound suggests that RHC Ⅲ chain also takes effect through endocytosis and ultimately promotes wound healing.The rabbit ear scar model suggests that RHC Ⅲ chain inhibits scar proliferation by reducing the ratio of Col Ⅰ/Col Ⅲ.In summary,RHC Ⅲ chain was endocytosed by fibroblasts to promote native Col Ⅲ synthesis,as well as promote wound healing and reduce scar hyperplasia.
文摘Effective treatment of rheumatoid arthritis can be mediated by native chicken type II collagen(n CCII), recombinant peptide containing n CCII tolerogenic epitopes(CTEs), or a therapeutic DNA vaccine encoding the full-length CCOL2 A1 c DNA. As recombinant CCII(r CCII) might avoid potential pathogenic virus contamination during n CCII preparation or chromosomal integration and oncogene activation associated with DNA vaccines, here we evaluated the importance of propeptide and telopeptide domains on r CCII triple helix molecular assembly. We constructed p C-and p N-procollagen(without N-or Cpropeptides, respectively) as well as CTEs located in the triple helical domain lacking both propeptides and telopeptides, and expressed these in yeast Pichia pastoris host strain GS115(his4, Mut+) simultaneously with recombinant chicken prolyl-4-hydroxylase α and β subunits. Both p C-and p N-procollagen monomers accumulated inside P. pastoris cells, whereas CTE was assembled into homotrimers with stable conformation and secreted into the supernatants, suggesting that the large molecular weight p C-or p N-procollagens were retained within the endoplasmic reticulum whereas the smaller CTEs proceeded through the secretory pathway. Furthermore, resulting recombinant chicken type II collagen p Cα1(II) can induce collagen-induced arthritis(CIA) rat model, which seems to be as effective as the current standard n CCII. Notably, protease digestion assays showed that r CCII could assemble in the absence of C-and N-propeptides or telopeptides. These findings provide new insights into the minimal structural requirements for r CCII expression and folding.
基金supported by National Key R&D Program of China(Grant No.2022YFC2401800)National Natural Science Foundation of China(Grant No.32301116)Sichuan Science and Technology Program(Grant No.2023 NSFSC0996).
文摘Collagen, recognized as the primary structural component of human skin, is essential for preserving dermal integrity and function. Its progressive depletion has been closely associated with structural deterioration of the dermis and the visible signs of skin aging. Among current therapeutic strategies, the injection of exogenous collagen has been established as an effective method for alleviating aging-related skin changes. In the present study, a comprehensive evaluation was conducted to assess the injectability, cellular interactions, and photoaging repair efficacy of recombinant human collagen type III(RHC). The RHC solution was found to demonstrate favorable injectability and support the adhesion and chemotactic behavior of L929 cells, while also upregulating the expression of type I and type III collagen. In co-culture systems with lipopolysaccharide-stimulated macrophages, RHC treatment suppressed macrophage proliferation and reduced the production of proinflammatory cytokines, suggesting notable immunomodulatory properties. Upon intradermal injection of RHC into photoaged rat skin, an increased density of dermal collagen fibers was observed, accompanied by a more organized and uniform fiber arrangement. Additionally, hydroxyproline content and the expressions of collagen I and III were markedly elevated in the RHC group compared with the control and hyaluronic acid groups. Collectively, these findings suggest that RHC holds considerable promise as a therapeutic agent for both medical and cosmetic purposes targeting the restoration and maintenance of youthful skin characteristics.
基金supported by the National Natural Science Foundation of China(32101107)CAMS Innovation Fund for Medical Sciences(2021-I2M-5-013).
文摘Anti-inflammation and anti-coagulation are the primary requirements for cardiovascular stents and also the widely accepted trajectory for multi-functional modification.In this work,we proposed an extracellular matrix(ECM)-mimetic coating for cardiovascular stents with the amplified functionalization of recombinant humanized collagen type III(rhCOL III),where the biomimetics were driven by structure mimicry and component/function mimicry.Briefly,the structure-mimic was constructed by the formation of a nanofiber(NF)structure via the polymerization of polysiloxane with a further introduction of amine groups as the nanofibrous layer.The fiber network could function as a three-dimensional reservoir to support the amplified immobilization of rhCoL III.The rhCOL III was tailored for anti-coagulant,anti-inflammatory and endothelialization promotion properties,which endows the ECM-mimetic coating with desired surface functionalities.Stent implantation in the abdominal aorta of rabbits was conducted to validate the in vivo re-endothelialization of the ECM-mimetic coating.The mild inflammatory responses,anti-thrombotic property,promotion of endothelialization and suppression of excessive neointimal hyperplasia confirmed that the ECM-mimetic coating provided a promising approach for the modification of vascular implants.
基金supported by National Key Research and Development Programs(2022YFB3807303 and 2022YFB3807305),National Natural Science Foundation of China(32101107)and CAMS InnovationFundforMedical Sciences(2021-12M-5-013)。
文摘Bioprosthetic heart valve(BHV)replacement has been the predo-minant treatment for severe heart valve diseases over decades.Most clinically available BHVs are crosslinked by glutaraldehyde(GLUT),while the high toxicity of residual GLUT could initiate calcification,severe thrombosis,and delayed endothelializa-tion.Here,we construed a mechanically integrating robust hydrogel-tissue hybrid to improve the performance of BHVs.In particular,recombinant humanized coilagen type Ⅲ(rhCOLⅢ),which was precisely customized with anti-coagulant and pro-endothelialization bioactivity,was first incorporated into the polyvinyl alcohol(PVA)-based hydrogel via hydrogen bond interactions.Then,tannic acid was introduced to enhance the mechanicalperfo of PVA-based hvdrogel and interfacial bonding between the hydrogel layer and bio-derived tissue due to the strong affinity for a wide range of substrates.In vitro and in vivo experimental results confirmed that the GLUT-crosslinked BHVs modified by the robust PVA-based hydrogel embedded rhCOLII and TA possessed long-term anti-coagulant,accelerated endothelialization,mild inflammatory response and anti-calcification properties.Therefore,our mechanically integrating robust hydrogel-tissue hybrid strategy showed the potential to enhance the service function and prolong the service life of the BHVs after implantation.
基金The study was supported by the National Natural Science Foundation of China （No. 30970880）, the Natural Science Foundation of the Jiangsu Province （No. BK20130342）, and the Jiangsu Planned Projects for Postdoctoral Research Funds （No. 1301069C）.
文摘Background Spinal cord injury （SCI） is a serious neurological injury that often leads to permanent disabilities for the victims. The aim of this study was to determine the effects of glial-derived neurotrophic factor （GDNF） mediated by recombinant adeno-associated virus type 2 （rAAV2） alone or in combination with early rehabilitation training on SCI. Methods SCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats. Then besides the sham operation group, the SCI rats were randomly divided into four groups： natural healing group, gene therapy group, rehabilitation training group, and combination therapy group （gene therapy in combination with rehabilitation training）. Motor dysfunction, protein expression of GDNF, edema formation, and cell injury were examined 7, 14, and 21 days after trauma. Results The topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF, especially after the 14th day, and could protect the motor neuron cells. Early rehabilitative treatment resulted in significantly improved motor function, reduced edema formation, and protected the cells from injury, especially after the 7th and 14th days, and increased the GDNF expression in the damaged area, which was most evident after Day 14. The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days. Conclusion These observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.
基金supported by National Key R&D Program of China(Grant No.2022YFC2401800)National Natural Science Foundation of China(Grant No.32301116)Sichuan Science and Technology Program(Grant No.2023NSFSC0996)
文摘The objective of regenerative wound healing dressings is to accelerate skin tissue regeneration and restore normal physiological function at wound sites.Achieving this goal requires biomaterials capable of repairing distinct phases of wound healing in a way that balanc es material function,degradation,safety,and tissue growth.In this study,we introduced a novel dual-stage wound dressing system comprising methacrylic anhydride-modified recombinant humanized type Ⅲ collagen(rhCol Ⅲ-MA) and methacrylic anhydride-modified dopamine(DMA)(RMDM),which was synthesized through free radical polymerization and π-π stacking.Within this system,RMDM was formulated into two forms with identic al compositions:hydrogel and sponge,tailored for application across various stages of wound repair.These materials displayed favorable hemocompatibility,biocompatibility,antioxidant properties,and angiogenic potential in vitro.Moreover,the in vivo experiments also demonstrated that sponges could rapidly stop the bleeding of wounds in mouse tail amputation and liver incision models.Notably,the sponge/gel(S/G) system accelerated wound healing compared to individual sponge and gel treatments in a rat full-thickness skin wound model,underscoring the synergistic benefits of combining sponge and gel materials for wound repair at different stages.Therefo re,this research provides valuable insights into designing advanced biomaterials that can be tailored to specific stages of wound healing,which may have significant potential for biomedical applications.
