Lithium-sulfur(Li-S) battery is one of the best candidates for the next-generation energy storage system due to its high theoretical capacity(1675 mA h-1),low cost and environment friendliness.However,lithium(Li) dend...Lithium-sulfur(Li-S) battery is one of the best candidates for the next-generation energy storage system due to its high theoretical capacity(1675 mA h-1),low cost and environment friendliness.However,lithium(Li) dendrites formation and polysulfide shuttle effect are two major challenges that limit the commercialization of Li-S batteries.Here we design a facile bifunctional interlayer of gelatin-based fibers(GFs),aiming to protect the Li anode surface from the dendrites growth and also hinder the polysulfide shuttle effect.We reveal that the 3D structural network of GFs layer with abundant polar sites helps to homogenize Li-ion flux,leading to uniform Li-ion deposition.Meanwhile,the polar moieties also immobilize the lithium polysulfides and protect the Li metal from the side-reaction.As a result,the anodeprotected batteries have shown significantly enhanced performance.A high coulombic efficiency of 96% after 160 cycles has been achieved in the Li-Cu half cells.The Li-Li symmetric cells exhibit a prolonged lifespan for 800 h with voltage hysteresis(10 mV).With the as-prepared GFs layer,the Li-S battery shows approximately 14% higher capacity retention than the pristine battery at 0.5 C after 100 cycles.Our work presents that this gelatin-based bi-functional interlayer provides a viable strategy for the manufacturing of advanced Li-S batteries.展开更多
The significance of bioink suitability for the extrusion bioprinting of tissue-like constructs cannot be overemphasized.Gelatin,derived from the hydrolysis of collagen,not only can mimic the extracellular matrix to imm...The significance of bioink suitability for the extrusion bioprinting of tissue-like constructs cannot be overemphasized.Gelatin,derived from the hydrolysis of collagen,not only can mimic the extracellular matrix to immensely support cell function,but also is suitable for extrusion under certain conditions.Thus,gelatin has been recognized as a promising bioink for extrusion bioprinting.However,the development of a gelatin-based bioink with satisfactory printability and bioactivity to fabricate complex tissue-like constructs with the desired physicochemical properties and biofunctions for a specific biomedical application is still in its infancy.Therefore,in this review,we aim to comprehensively summarize the state-of-the-art methods of gelatin-based bioink application for extrusion bioprinting.Wefirstly outline the properties and requirements of gelatin-based bioinks for extrusion bioprinting,highlighting the strategies to overcome their main limitations in terms of printability,structural stability and cell viability.Then,the challenges and prospects are further discussed regarding the development of ideal gelatin-based bioinks for extrusion bioprinting to create complex tissue-like constructs with preferable physicochemical properties and biofunctions.展开更多
Functionalized hydrogels stimulate the migration and morphogenesis of endothelial cells(ECs)and are useful substrates for wound healing.The present study investigates the feasibility of covalent conjugation of taurine...Functionalized hydrogels stimulate the migration and morphogenesis of endothelial cells(ECs)and are useful substrates for wound healing.The present study investigates the feasibility of covalent conjugation of taurine(Tau)on a gelatin-based hydrogel.This hydrogel is expected to maintain positive charged growth factors such as basic fibroblast growth factor(bFGF)and vascular endothelial growth factors(VEGFs)near ECs within the hydrogel microenvironment.The gelatin was conjugated with hydroxyl phenol(Ph)and Tau moieties,and in following that Ph residues were crosslinked through a horseradish peroxidase-catalyzed reaction.The migration characteristics of ECs were analyzed by scratch migration assay and microparticle-based cell migration assay.Cellular morphology and amounts of angiopoietin 1(Ang 1),bFGF,and VEGF proteins were evaluated for encapsulated cells.The potential of synthesized hydrogels in wound healing was assessed by the percentage of reduction from the original wound size and histopathological analyses of rat skin.The incorporated Tau molecules within the hydrogel remained stable through covalent bonds during incubation.During extended incubation,the gelatin-based hydrogel conjugated with Tau improved the migration distance and number of existing migrated ECs.Immobilized Tau within the gelatin-based hydrogel induced high motility of ECs,accompanied by robust cytoskeleton extension and a cell subpopulation that expressed CD44 and CD31 receptors as well as enhancement of Ang 1,bFGF,and VEGF.We found that injectable Gel-Ph-Tau effectively improves wound-healing parameters.展开更多
Articular cartilage injury is a common disease in the field of orthopedics.Because cartilage has poor self-repairing ability,medical intervention is needed.Using melt electro-writing(MEW)technology,tissue engineering ...Articular cartilage injury is a common disease in the field of orthopedics.Because cartilage has poor self-repairing ability,medical intervention is needed.Using melt electro-writing(MEW)technology,tissue engineering scaffolds with high porosity and high precision can be prepared.However,ordinary materials,especially natural polymer materials,are difficult to print.In this study,gelatin was mixed with poly(lactic-co-glycolic acid)to prepare high-concentration and high-viscosity printer ink,which had good printability and formability.A composite scaffold with full-layer TGF-β1 loading mixed with hydroxyapatite was prepared,and the scaffold was implanted at the cartilage injury site;microfracture surgery was conducted to induce the mesenchyme in the bone marrow.Quality stem cells thereby promoted the repair of damaged cartilage.In summary,this study developed a novel printing method,explored the molding conditions based on MEW printing ink,and constructed a bioactive cartilage repair scaffold.The scaffold can use autologous bone marrow mesenchymal stem cells and induce their differentiation to promote cartilage repair.展开更多
Biopolymer microbeads present substantial benefits for cell expansion,tissue engineering,and drug release applications.However,a fabrication system capable of producing homogeneous microspheres with high precision and...Biopolymer microbeads present substantial benefits for cell expansion,tissue engineering,and drug release applications.However,a fabrication system capable of producing homogeneous microspheres with high precision and controllability for cell proliferation,passaging,harvesting and downstream application is limited.Therefore,we developed a co-flow microfluidics-based system for the generation of uniform and size-controllable gelatin-based microcarriers(GMs)for mesenchymal stromal cells(MSCs)expansion and tissue engineering.Our evaluation of GMs revealed superior homogeneity and efficiency of cellular attachment,expansion and harvest,and MSCs expanded on GMs exhibited high viability while retaining differentiation multipotency.Optimization of passaging and harvesting protocols was achieved through the addition of blank GMs and treatment with collagenase,respectively.Furthermore,we demonstrated that MSC-loaded GMs were printable and could serve as building blocks for tissue regeneration scaffolds.These results suggested that our platform held promise for the fabrication of uniform GMs with downstream application of MSC culture,expansion and tissue engineering.展开更多
Degenerative spine pathologies,including intervertebral disc(IVD)degeneration,present a significant healthcare challenge due to their association with chronic pain and disability.This study explores an innovative appr...Degenerative spine pathologies,including intervertebral disc(IVD)degeneration,present a significant healthcare challenge due to their association with chronic pain and disability.This study explores an innovative approach to IVD regeneration utilizing 3D bioprinting technology,specifically visible light-based digital light processing,to fabricate tissue scaffolds that closely mimic the native architecture of the IVD.Utilizing a hybrid bioink composed of gelatin methacrylate(GelMA)and poly(ethylene glycol)diacrylate(PEGDA)at a 10%concentration,we achieved enhanced printing fidelity and mechanical properties suitable for load-bearing applications such as the IVD.Preconditioning rat bone marrow-derived mesenchymal stem cell spheroids with chondrogenic media before incorporating them into the GelMA-PEGDA scaffold further promoted the regenerative capabilities of this system.Our findings demonstrate that this bioprinted scaffold not only supports cell viability and integration but also contributes to the restoration of disc height in a rat caudal disc model without inducing adverse inflammatory responses.The study underscores the potential of combining advanced bioprinting techniques and cell preconditioning strategies to develop effective treatments for IVD degeneration and other musculoskeletal disorders,highlighting the need for further research into the dynamic interplay between cellular migration and the hydrogel matrix.展开更多
Traditional hemostatic materials are difficult to meet the needs of non-compressible bleeding and for coagulopathic patients.In addition,open wounds are susceptible to infection,and then develop into chronic wounds.Ho...Traditional hemostatic materials are difficult to meet the needs of non-compressible bleeding and for coagulopathic patients.In addition,open wounds are susceptible to infection,and then develop into chronic wounds.However,the development of integrated dressings that do not depend on coagulation pathway and improve the microenvironment of chronic wounds remains a challenge.Inspired by the porous structure and composition of the natural extracellular matrix,adipic dihydrazide modified gelatin(GA),dodecylamine-grafted hyaluronic acid(HD),and MnO_(2) nanozyme(manganese dioxide)@DFO(deferoxamine)@PDA(polydopamine)(MDP)nanoparticles were combined to prepare GA/HD/MDP cryogels through amidation reaction and hydrogen bonding.These cryogels exhibited good fatigue resistance,photothermal antibacterial(about 98%killing ratios of both Escherichia coli and methicillin-resistant Staphylococcus aureus(MRSA)after 3 min near-infrared irradiation),reactive oxygen species scavenging,oxygen release,and angiogenesis properties.Furthermore,in the liver defect model of rats with coagulopathy,the cryogel displayed less bleeding and shorter hemostasis time than commercial gelatin sponge.In MRSA-infected diabetic wounds,the cryogel could decrease wound inflammation and oxidative stress,alleviate the hypoxic environment,promote collagen deposition,and induce vascular regeneration,showing a better repair effect compared with the Tegaderm^(TM)film.These results indicated that GA/HD/MDP cryogels have great potential in non-compressible hemorrhage for coagulopathic patients and in healing infected wounds for diabetic patients.展开更多
Micro-/nano-patterns on hydrogels are widely used in cell patterning.However,manufacturing molds with traditional lithography is time-consuming and expensive.In addition,the excessive demolding force can easily damage...Micro-/nano-patterns on hydrogels are widely used in cell patterning.However,manufacturing molds with traditional lithography is time-consuming and expensive.In addition,the excessive demolding force can easily damage patterns since biocompatible hydrogels are ultra-soft or brittle.Here,we presented a novel method for rapid and mass fabrication of cell patterns.High-precision three-dimensional(3D)printing was used to manufacture a mold with a resolution of 2µm,and the gelatin-based hydrogel was cured by thermal–photo-crosslinking so that the low-concentration and low-substitutionrate hydrogel could be demolded successfully.We found that pre-cooling before illumination made gelatin-based hydrogels resilient due to the partial regain of triple-helix structures.With this method,arbitrarily customized hydrogel patterns with a feature size of 6–80µm can be fabricated stably and at low cost.When cardiomyocytes were seeded on ultra-soft hydrogels with parallel groove structures,a consistent and spontaneous beating with 216 beats per minute(BPM)could be observed,approaching the natural beating rate of rat hearts(300 BPM).Overall,this work provides a general scheme for manufacturing cell patterns which has great potential for cell ethology and tissue repair.展开更多
Radiation damage can cause a series of gastrointestinal(GI)tract diseases.The development of safe and effective GI tract radioprotectants still remains a great challenge clinically.Here,we firstly report an oral radio...Radiation damage can cause a series of gastrointestinal(GI)tract diseases.The development of safe and effective GI tract radioprotectants still remains a great challenge clinically.Here,we firstly report an oral radioprotectant Gel@GYY that integrates a porous gelatin-based(Gel)hydrogel and a pH-responsive hydrogen sulfide(H2S)donor GYY4137(morpholin-4-ium 4 methoxyphenyl(morpholino)phosphinodithioate).Gel@GYY has a remarkable adhesion ability and long retention time,which not only enables responsive release of low-dose H2S in stomach and subsequently sustained release of H2S in the whole intestinal tract especially in the colon,but also ensures a close contact between H2S and GI tract.The released H2S can effectively scavenge free radicals induced by X-ray radiation,reduce lipid peroxidation level,repair DNA damage and recover vital superoxide dismutase and glutathione peroxidase activities.Meanwhile,the released H2S inhibits radiation-induced activation of nuclear factorκB(NF-κB),thus reducing inflammatory cytokines levels in GI tract.After treatment,Gel@GYY displays efficient excretion from mice body due to its biodegradability.This work provides a new insight for therapeutic application of intelligent H2S-releasing oral delivery system and potential alternative to clinical GI physical damage protectant.展开更多
Regeneration of articular cartilage defects remains challenging owing to its inherently limited endogenous cell source and self-renewal capacity.Although cell therapy has shown promise in regenerating articular cartil...Regeneration of articular cartilage defects remains challenging owing to its inherently limited endogenous cell source and self-renewal capacity.Although cell therapy has shown promise in regenerating articular cartilage,maintaining cellular functional activity and precisely delivering cells to the defect site remain significant obstacles.Herein,we present a bioprinting strategy to fabricate a cartilage precursor cell(CPCs)-loaded gelatin-based scaffold,which can precisely deliver cells,maintain cellular function,and thus enhance cartilage regeneration.First,benefiting from the modification of quadruplehydrogen-bonded ureyl pyrimidinone(UPy),gelatin modified with UPy(Gel-UPy)bioink demonstrated a temperature-programmable viscosity,enabling cell-holding stability during the printing process,and extrudable printability at a near physiological temperature.Then,through the enzymatic solidification of transglutaminase(TG),the bioprinted cell-laden scaffold(Gel-UPy@TG)was enhanced in substantial mechanical stability while maintaining a high cell survival rate.Finally,when implanted in a full-layer cartilage defect model of rabbit femoral trochlea,the bioprinted scaffold preserved the chondrogenic capacity of CPCs in the defect site and communicated with the surrounding cells,thereby accelerating the repair process of cartilage defects.展开更多
The effect of enzymatic crosslinking by microbial transglutaminase on the physico-chemical properties of gelatin-based films incorporated with lysozyme were investigated.Increase in the crosslinking degree of gelatin ...The effect of enzymatic crosslinking by microbial transglutaminase on the physico-chemical properties of gelatin-based films incorporated with lysozyme were investigated.Increase in the crosslinking degree of gelatin with microbial transglutaminase concentration in film-forming suspensions was correlated with a decrease of films thickness.Moreover,the enhancement in crosslinking resulted in a decrease of the solubility in water,as well as of the extent of swelling degree,and of the water vapor permeability of films and in an increase of films tensile strength.The kinetics of release at 4◦C of lysozyme from control non-reticulated films and reticulated films to either sodium acetate buffer,or 2%(w/v)agar gels in direct contact were compared.Interestingly,the kinetics of release of lysozyme were always slower from crosslinked films than from control films.This difference was higher for lysozyme release to agar gels,which was dominated by Fickian diffusion.Enzymatic crosslinking by microbial transglutaminase of gelatin-based films incorporated with lysozyme can thus effectively control the release of this food preservative.展开更多
基金supported by the National Natural Science Foundation of China (No. 51861165101)。
文摘Lithium-sulfur(Li-S) battery is one of the best candidates for the next-generation energy storage system due to its high theoretical capacity(1675 mA h-1),low cost and environment friendliness.However,lithium(Li) dendrites formation and polysulfide shuttle effect are two major challenges that limit the commercialization of Li-S batteries.Here we design a facile bifunctional interlayer of gelatin-based fibers(GFs),aiming to protect the Li anode surface from the dendrites growth and also hinder the polysulfide shuttle effect.We reveal that the 3D structural network of GFs layer with abundant polar sites helps to homogenize Li-ion flux,leading to uniform Li-ion deposition.Meanwhile,the polar moieties also immobilize the lithium polysulfides and protect the Li metal from the side-reaction.As a result,the anodeprotected batteries have shown significantly enhanced performance.A high coulombic efficiency of 96% after 160 cycles has been achieved in the Li-Cu half cells.The Li-Li symmetric cells exhibit a prolonged lifespan for 800 h with voltage hysteresis(10 mV).With the as-prepared GFs layer,the Li-S battery shows approximately 14% higher capacity retention than the pristine battery at 0.5 C after 100 cycles.Our work presents that this gelatin-based bi-functional interlayer provides a viable strategy for the manufacturing of advanced Li-S batteries.
基金support for this work from the National Key R&D Program of China(No.2018YFA0703100)the National Natural Sci-ence Foundation of China(Nos.32122046,82072082,and 32000959)+2 种基金the Youth Innovation Promotion Association of CAS(No.2019350)the Guangdong Natural Science Foundation(No.2019A1515111197)the Shenzhen Fundamental Research Foun-dation(Nos.JCYJ20190812162809131,JCYJ20200109114006014,JCYJ20210324113001005,and JCYJ20210324115814040).
文摘The significance of bioink suitability for the extrusion bioprinting of tissue-like constructs cannot be overemphasized.Gelatin,derived from the hydrolysis of collagen,not only can mimic the extracellular matrix to immensely support cell function,but also is suitable for extrusion under certain conditions.Thus,gelatin has been recognized as a promising bioink for extrusion bioprinting.However,the development of a gelatin-based bioink with satisfactory printability and bioactivity to fabricate complex tissue-like constructs with the desired physicochemical properties and biofunctions for a specific biomedical application is still in its infancy.Therefore,in this review,we aim to comprehensively summarize the state-of-the-art methods of gelatin-based bioink application for extrusion bioprinting.Wefirstly outline the properties and requirements of gelatin-based bioinks for extrusion bioprinting,highlighting the strategies to overcome their main limitations in terms of printability,structural stability and cell viability.Then,the challenges and prospects are further discussed regarding the development of ideal gelatin-based bioinks for extrusion bioprinting to create complex tissue-like constructs with preferable physicochemical properties and biofunctions.
文摘Functionalized hydrogels stimulate the migration and morphogenesis of endothelial cells(ECs)and are useful substrates for wound healing.The present study investigates the feasibility of covalent conjugation of taurine(Tau)on a gelatin-based hydrogel.This hydrogel is expected to maintain positive charged growth factors such as basic fibroblast growth factor(bFGF)and vascular endothelial growth factors(VEGFs)near ECs within the hydrogel microenvironment.The gelatin was conjugated with hydroxyl phenol(Ph)and Tau moieties,and in following that Ph residues were crosslinked through a horseradish peroxidase-catalyzed reaction.The migration characteristics of ECs were analyzed by scratch migration assay and microparticle-based cell migration assay.Cellular morphology and amounts of angiopoietin 1(Ang 1),bFGF,and VEGF proteins were evaluated for encapsulated cells.The potential of synthesized hydrogels in wound healing was assessed by the percentage of reduction from the original wound size and histopathological analyses of rat skin.The incorporated Tau molecules within the hydrogel remained stable through covalent bonds during incubation.During extended incubation,the gelatin-based hydrogel conjugated with Tau improved the migration distance and number of existing migrated ECs.Immobilized Tau within the gelatin-based hydrogel induced high motility of ECs,accompanied by robust cytoskeleton extension and a cell subpopulation that expressed CD44 and CD31 receptors as well as enhancement of Ang 1,bFGF,and VEGF.We found that injectable Gel-Ph-Tau effectively improves wound-healing parameters.
基金This work was supported by Shanghai Ninth People’s Hospital(grant number XK2019013)National Natural Science Foundation of China(No.81802131,82002293)China Postdoctoral Science Foundation(No.2019T120347).
文摘Articular cartilage injury is a common disease in the field of orthopedics.Because cartilage has poor self-repairing ability,medical intervention is needed.Using melt electro-writing(MEW)technology,tissue engineering scaffolds with high porosity and high precision can be prepared.However,ordinary materials,especially natural polymer materials,are difficult to print.In this study,gelatin was mixed with poly(lactic-co-glycolic acid)to prepare high-concentration and high-viscosity printer ink,which had good printability and formability.A composite scaffold with full-layer TGF-β1 loading mixed with hydroxyapatite was prepared,and the scaffold was implanted at the cartilage injury site;microfracture surgery was conducted to induce the mesenchyme in the bone marrow.Quality stem cells thereby promoted the repair of damaged cartilage.In summary,this study developed a novel printing method,explored the molding conditions based on MEW printing ink,and constructed a bioactive cartilage repair scaffold.The scaffold can use autologous bone marrow mesenchymal stem cells and induce their differentiation to promote cartilage repair.
基金supported by the National Natural Science Foundation of China(Grant No.52075285)the Applied Basic Research Project of Sichuan Province(Grant No.2021YJ0563).
文摘Biopolymer microbeads present substantial benefits for cell expansion,tissue engineering,and drug release applications.However,a fabrication system capable of producing homogeneous microspheres with high precision and controllability for cell proliferation,passaging,harvesting and downstream application is limited.Therefore,we developed a co-flow microfluidics-based system for the generation of uniform and size-controllable gelatin-based microcarriers(GMs)for mesenchymal stromal cells(MSCs)expansion and tissue engineering.Our evaluation of GMs revealed superior homogeneity and efficiency of cellular attachment,expansion and harvest,and MSCs expanded on GMs exhibited high viability while retaining differentiation multipotency.Optimization of passaging and harvesting protocols was achieved through the addition of blank GMs and treatment with collagenase,respectively.Furthermore,we demonstrated that MSC-loaded GMs were printable and could serve as building blocks for tissue regeneration scaffolds.These results suggested that our platform held promise for the fabrication of uniform GMs with downstream application of MSC culture,expansion and tissue engineering.
基金supported by NIH Grant(T32GM065841),Mayo Foundation for Education and Research.
文摘Degenerative spine pathologies,including intervertebral disc(IVD)degeneration,present a significant healthcare challenge due to their association with chronic pain and disability.This study explores an innovative approach to IVD regeneration utilizing 3D bioprinting technology,specifically visible light-based digital light processing,to fabricate tissue scaffolds that closely mimic the native architecture of the IVD.Utilizing a hybrid bioink composed of gelatin methacrylate(GelMA)and poly(ethylene glycol)diacrylate(PEGDA)at a 10%concentration,we achieved enhanced printing fidelity and mechanical properties suitable for load-bearing applications such as the IVD.Preconditioning rat bone marrow-derived mesenchymal stem cell spheroids with chondrogenic media before incorporating them into the GelMA-PEGDA scaffold further promoted the regenerative capabilities of this system.Our findings demonstrate that this bioprinted scaffold not only supports cell viability and integration but also contributes to the restoration of disc height in a rat caudal disc model without inducing adverse inflammatory responses.The study underscores the potential of combining advanced bioprinting techniques and cell preconditioning strategies to develop effective treatments for IVD degeneration and other musculoskeletal disorders,highlighting the need for further research into the dynamic interplay between cellular migration and the hydrogel matrix.
基金jointly supported by the National Natural Science Foundation of China(No.52273149,82171143)Fundamental Research Funds for the Central Universities and the World-Class Universities(Disciplines)Characteristic Development Guidance Funds for the Central Universities.
文摘Traditional hemostatic materials are difficult to meet the needs of non-compressible bleeding and for coagulopathic patients.In addition,open wounds are susceptible to infection,and then develop into chronic wounds.However,the development of integrated dressings that do not depend on coagulation pathway and improve the microenvironment of chronic wounds remains a challenge.Inspired by the porous structure and composition of the natural extracellular matrix,adipic dihydrazide modified gelatin(GA),dodecylamine-grafted hyaluronic acid(HD),and MnO_(2) nanozyme(manganese dioxide)@DFO(deferoxamine)@PDA(polydopamine)(MDP)nanoparticles were combined to prepare GA/HD/MDP cryogels through amidation reaction and hydrogen bonding.These cryogels exhibited good fatigue resistance,photothermal antibacterial(about 98%killing ratios of both Escherichia coli and methicillin-resistant Staphylococcus aureus(MRSA)after 3 min near-infrared irradiation),reactive oxygen species scavenging,oxygen release,and angiogenesis properties.Furthermore,in the liver defect model of rats with coagulopathy,the cryogel displayed less bleeding and shorter hemostasis time than commercial gelatin sponge.In MRSA-infected diabetic wounds,the cryogel could decrease wound inflammation and oxidative stress,alleviate the hypoxic environment,promote collagen deposition,and induce vascular regeneration,showing a better repair effect compared with the Tegaderm^(TM)film.These results indicated that GA/HD/MDP cryogels have great potential in non-compressible hemorrhage for coagulopathic patients and in healing infected wounds for diabetic patients.
基金sponsored by the National Key Research and Development Program of China (No.2018YFA0703000)the National Natural Science Foundation of China (Nos.T2121004 and U1909218)supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No.ZYYCXTD-D-202002)。
文摘Micro-/nano-patterns on hydrogels are widely used in cell patterning.However,manufacturing molds with traditional lithography is time-consuming and expensive.In addition,the excessive demolding force can easily damage patterns since biocompatible hydrogels are ultra-soft or brittle.Here,we presented a novel method for rapid and mass fabrication of cell patterns.High-precision three-dimensional(3D)printing was used to manufacture a mold with a resolution of 2µm,and the gelatin-based hydrogel was cured by thermal–photo-crosslinking so that the low-concentration and low-substitutionrate hydrogel could be demolded successfully.We found that pre-cooling before illumination made gelatin-based hydrogels resilient due to the partial regain of triple-helix structures.With this method,arbitrarily customized hydrogel patterns with a feature size of 6–80µm can be fabricated stably and at low cost.When cardiomyocytes were seeded on ultra-soft hydrogels with parallel groove structures,a consistent and spontaneous beating with 216 beats per minute(BPM)could be observed,approaching the natural beating rate of rat hearts(300 BPM).Overall,this work provides a general scheme for manufacturing cell patterns which has great potential for cell ethology and tissue repair.
基金the National Natural Science Foundation of China(Nos.22175182,21471103)Sheng Yuan Cooperation(No.2021SYHZ0048)+1 种基金Beijing Natural Science Foundation(No.2202064)the directional institutionalized scientific research platform relies on Beijing Synchrotron Radiation Facility of Chinese Academy of Sciences.
文摘Radiation damage can cause a series of gastrointestinal(GI)tract diseases.The development of safe and effective GI tract radioprotectants still remains a great challenge clinically.Here,we firstly report an oral radioprotectant Gel@GYY that integrates a porous gelatin-based(Gel)hydrogel and a pH-responsive hydrogen sulfide(H2S)donor GYY4137(morpholin-4-ium 4 methoxyphenyl(morpholino)phosphinodithioate).Gel@GYY has a remarkable adhesion ability and long retention time,which not only enables responsive release of low-dose H2S in stomach and subsequently sustained release of H2S in the whole intestinal tract especially in the colon,but also ensures a close contact between H2S and GI tract.The released H2S can effectively scavenge free radicals induced by X-ray radiation,reduce lipid peroxidation level,repair DNA damage and recover vital superoxide dismutase and glutathione peroxidase activities.Meanwhile,the released H2S inhibits radiation-induced activation of nuclear factorκB(NF-κB),thus reducing inflammatory cytokines levels in GI tract.After treatment,Gel@GYY displays efficient excretion from mice body due to its biodegradability.This work provides a new insight for therapeutic application of intelligent H2S-releasing oral delivery system and potential alternative to clinical GI physical damage protectant.
基金supported by the National Key R&D Program of China(Grant No.2022YFA1207502)the National Natural Science Foundation of China(Grant No.92468106)+2 种基金the Natural Science Foundation of Guangdong Province in China(Grant No.2024B1515040018)the Shenzhen Fundamental Research Foundation(Grant Nos.JCYJ20220818101613028,JCYJ20220531100602004,JSGGKQTD20210831174330015)the Shenzhen Medical Research Fund(Grant No.A2403025)。
文摘Regeneration of articular cartilage defects remains challenging owing to its inherently limited endogenous cell source and self-renewal capacity.Although cell therapy has shown promise in regenerating articular cartilage,maintaining cellular functional activity and precisely delivering cells to the defect site remain significant obstacles.Herein,we present a bioprinting strategy to fabricate a cartilage precursor cell(CPCs)-loaded gelatin-based scaffold,which can precisely deliver cells,maintain cellular function,and thus enhance cartilage regeneration.First,benefiting from the modification of quadruplehydrogen-bonded ureyl pyrimidinone(UPy),gelatin modified with UPy(Gel-UPy)bioink demonstrated a temperature-programmable viscosity,enabling cell-holding stability during the printing process,and extrudable printability at a near physiological temperature.Then,through the enzymatic solidification of transglutaminase(TG),the bioprinted cell-laden scaffold(Gel-UPy@TG)was enhanced in substantial mechanical stability while maintaining a high cell survival rate.Finally,when implanted in a full-layer cartilage defect model of rabbit femoral trochlea,the bioprinted scaffold preserved the chondrogenic capacity of CPCs in the defect site and communicated with the surrounding cells,thereby accelerating the repair process of cartilage defects.
文摘The effect of enzymatic crosslinking by microbial transglutaminase on the physico-chemical properties of gelatin-based films incorporated with lysozyme were investigated.Increase in the crosslinking degree of gelatin with microbial transglutaminase concentration in film-forming suspensions was correlated with a decrease of films thickness.Moreover,the enhancement in crosslinking resulted in a decrease of the solubility in water,as well as of the extent of swelling degree,and of the water vapor permeability of films and in an increase of films tensile strength.The kinetics of release at 4◦C of lysozyme from control non-reticulated films and reticulated films to either sodium acetate buffer,or 2%(w/v)agar gels in direct contact were compared.Interestingly,the kinetics of release of lysozyme were always slower from crosslinked films than from control films.This difference was higher for lysozyme release to agar gels,which was dominated by Fickian diffusion.Enzymatic crosslinking by microbial transglutaminase of gelatin-based films incorporated with lysozyme can thus effectively control the release of this food preservative.
