In clinical settings,regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods,restricted bone growth medications,and a scarcity of commercial bone gra...In clinical settings,regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods,restricted bone growth medications,and a scarcity of commercial bone grafts.To treat this life-threatening issue,improved biofunctional grafts capable of properly healing critical-sized bone defects are required.In this study,we effectively created anti-fracture hydrogel systems using spongy-like metal-organic(magnesium-phosphate)coordinated chitosan-modified injectable hydrogels(CPMg)loaded with a bioinspired neobavaisoflavone(NBF)component.The CPMg-NBF hydrogels showed outstanding anti-fracture capabilities during compression testing and retained exceptional mechanical stability even after 28 d of immersion in phosphatebuffered saline.They also demonstrated prolonged and stable release profiles of Mg^(2+)and NBF.Importantly,CPMg-NBF hydrogels revealed robust biphasic mineralization and were non-toxic to MC3T3-E1 cells.To better understand the underlying mechanism of Mg^(2+)and NBF component,as well as their synergistic effect on osteogenesis,we investigated the expression of key osteogenic proteins in the p38 MAPK and NOTCH pathways.Our results showed that CPMg-NBF hydrogels greatly increased the expression of osteogenic proteins(Runx2,OCN,OPN,BMPS and ALP).In vivo experiments showed that the implantation of CPMg-NBF hydrogels resulted in a significant increase in new bone growth within critical-sized calvarial defects.Based on these findings,we expect that the CPMg-NBF supramolecular hydrogel has tremendous promise for use as a therapeutic biomaterial for treating critical-sized calvarial defects.展开更多
Selective laser melting(SLM)is an emerging layer-wise additive manufacturing technique that can generate complex components with high performance.Particulate-reinforced aluminum matrix composites(PAMCs)are important m...Selective laser melting(SLM)is an emerging layer-wise additive manufacturing technique that can generate complex components with high performance.Particulate-reinforced aluminum matrix composites(PAMCs)are important materials for various applications due to the combined properties of Al matrix and reinforcements.Considering the advantages of SLM technology and PAMCs,the novel SLM PAMCs have been developed and researched in recent years.Therefore,the current research progress about the SLM PAMCs is reviewed.Firstly,special attention is paid to the solidification behavior of SLM PAMCs.Secondly,the important issues about the design and fabrication of high-performance SLM PAMCs,including the selection of reinforcement,the influence of parameters on the processing and microstructure,the defect evolution and phase control,are highlighted and discussed comprehensively.Thirdly,the performance and strengthening mechanism of SLM PAMCs are systematically figured out.Finally,future directions are pointed out on the advancement of high-performance SLM PAMCs.展开更多
Ti-6Al-4V specimens were fabricated by selective laser melting(SLM)to study the effect of thermal treatment on the phase transformation,elemental diffusion,microstructure,and mechanical properties.The results show tha...Ti-6Al-4V specimens were fabricated by selective laser melting(SLM)to study the effect of thermal treatment on the phase transformation,elemental diffusion,microstructure,and mechanical properties.The results show that vanadium enriches around the boundary ofαphases with increasing annealing temperature to 973 K,andα′phases transform intoα+βat 973 K.The typicalα′martensite microstructure transforms to fine-scale equiaxed microstructure at 973 K and the equiaxed microstructure significantly coarsens with increasing annealing temperature to 1273 K.The SLM Ti-6Al-4V alloy annealed at 973 K exhibits a well-balanced combination of strength and ductility((1305±25)MPa and(37±3)%,respectively).展开更多
High entropy alloys(HEAs)have recently received extensive attention due to their appealing mechani-cal performance given their simple phase formation.This study utilized laser powder bed fusion(LPBF)to fabricate high-...High entropy alloys(HEAs)have recently received extensive attention due to their appealing mechani-cal performance given their simple phase formation.This study utilized laser powder bed fusion(LPBF)to fabricate high-performance HEA components.By processing respective powder blends,LPBF enabled the fabrication of stronger composites with a uniformly distributed reinforcing phase.Here,the impact of varying content of nano-scale TiC(1-3 wt%)particles for strengthening the CoCrFeMnNi HEA was ex-plored.The microstructural features and mechanical properties of the HEA composites were investigated in detail.The introduction of nano-scale TiC into the HEA matrix encouraged the development of cross-scale hierarchical microstructure and eliminated the formation of oxide inclusions.Incorporating more nano-TiC led to a higher dislocation density and more refined microstructure in the HEA composites,whereas it posed little influence on the anisotropy of the HEA matrix which typically featured a<001>texture along the building direction.With an optimized content of nano-TiC(1-2 wt%),the strength-ductility trade-offcan be overcome by exploiting multiple strengthening mechanisms encompassing grain boundary strengthening,solid solution strengthening,Orowan strengthening,and dislocation strengthen-ing.The HEA composites showed a favored strength-ductility combination with a yield strength of 748-882 MPa,ultimate tensile strength of 931-1081 MPa,and fracture elongation of 23%-29%.This study demonstrates that the introduction of nano-scale TiC is an effective way to simultaneously improve the strength and ductility of additively manufactured HEA materials.展开更多
Al-7Si-0.5Mg-0.5Cu alloy specimens have been fabricated by selective laser melting(SLM).In this study,the effects of solution treatment,quenching,and artifi cial aging on the microstructural evolution,as well as mecha...Al-7Si-0.5Mg-0.5Cu alloy specimens have been fabricated by selective laser melting(SLM).In this study,the effects of solution treatment,quenching,and artifi cial aging on the microstructural evolution,as well as mechanical and wear properties,have been investigated.The as-prepared samples show a heterogeneous cellular microstructure with two different cell sizes composed ofα-Al and Si phases.After solution-treated and quenched(SQ)heat treatment,the cellular microstructure disappears,and coarse and lumpy Si phase precipitates and a rectangular Cu-rich phase were observed.Subsequent aging after solution-treated and quenched(SQA)heat treatment causes the formation of nanosized Cu-rich precipitates.The asprepared SLMs sample has good mechanical properties and wear resistance(compressive yield strength:215±6 MPa and wear rate 2×10^(-13)m^(3)/m).The SQ samples with lumpy Si particles have the lowest strength of 167±13 MPa and the highest wear rate of 6.18×10^(1-13)m^(3)/m.The formation of nanosized Cu-rich precipitates in the SQA samples leads to the highest compressive yield strength of 233±6 MPa and a good wear rate of 5.06×10^(-13)m^(3)/m.展开更多
Solar ultraviolet B(UVB)radiation is a major skin cancer-causing agent.Initiation,promotion,and progression are the diverse phases of UVB-induced carcinogenesis.Exposure to UVB causes abnormalities in a series of bioc...Solar ultraviolet B(UVB)radiation is a major skin cancer-causing agent.Initiation,promotion,and progression are the diverse phases of UVB-induced carcinogenesis.Exposure to UVB causes abnormalities in a series of biochemical and molecular pathways:thymine dimer formation,DNA damage,oxidative stress,inflammatory responses,and altered cell signaling,eventually resulting in tumor formation.The increased skin cancer rates urge researchers to develop more efficient drugs,but synthetic chemotherapeutic drugs have more contrary effects and drug resistance issues,which have been reported recently.The current review focuses on the relationship between microbes and cancer.Human skin acts as a barrier against the external environment and serves as a protective shield for its inhabitant microbiota,collectively called skin microbes.The gut microbiome plays a vital role in cancer therapy.Production of short-chain fatty acids(SCFAs)such as butyrate,acetate,and propionate by intestinal microbes has anti-cancer properties against various cancer cell lines.Yet,the knowledge of SCFAs produced by skin microbes remains yet to be elucidated exhaustively.In this review,we strive to summarize the findings of studies performed to date regarding the anti-cancer properties of SCFA against various cancer cell lines and provide insight into future directions in the skin microbiome field.展开更多
The study explores the processing and characterization of dense tungsten carbide(WC)–10 wt.%nickel(Ni)structures(WC-10Ni)built using laser powder bed fusion(LPBF).LPBF experimental trials were conducted at different ...The study explores the processing and characterization of dense tungsten carbide(WC)–10 wt.%nickel(Ni)structures(WC-10Ni)built using laser powder bed fusion(LPBF).LPBF experimental trials were conducted at different combinations of process parameters based on central composite design to develop process maps.Three samples built at different laser energy densities(LED of 460,381.7 and 300 J·m^(-3))with a 10 wt.%high relative density(>83.8%)were subjected to microstructural analysis,phase analysis,microhardness assessment,and abrasive wear testing.The characterizations focused on understanding the microstructure and mechanical behavior of LPBF-built WC-10Ni and developing a correlation between LED and material behavior.Higher LED resulted in keyhole porosity,while lower LED led to lack-of-fusion pores.The carbide particle size increased with LED,attributed to thermal cycling and coalescence during solidification.Higher LED also induced phase transformations,such as,the decomposition of WC into W_(2)C and the oxidation of Ni.Microhardness testing showed that the WC phase reached 1650 HV1,while the Ni matrix reached 1011 HV1.The abrasive wear testing demonstrated mass loss of<1%.Investigation of the wear scar resulted in the conclusion that the uniform distribution of WC particles in the Ni matrix contributed to this performance.The above studies indicate a positive correlation among relative density,hardness,and wear resistance.The study paves the way to understand the processing and material characteristics of LPBF-built WC-10Ni.展开更多
Microbial infections of bones,particularly after joint replacement surgery,are a common occurrence in clinical settings and often lead to osteomyelitis(OM).Unfortunately,current treatment approaches for OM are not sat...Microbial infections of bones,particularly after joint replacement surgery,are a common occurrence in clinical settings and often lead to osteomyelitis(OM).Unfortunately,current treatment approaches for OM are not satisfactory.To address this issue,this study focuses on the development and evaluation of an injectable magnesium oxide(MgO)nanoparticle(NP)-coordinated phosphocreatine-grafted chitosan hydrogel(CMPMg-VCM)loaded with varying amounts of vancomycin(VCM)for the treatment of OM.The results demonstrate that the loading of VCM does not affect the formation of the injectable hydrogel,and the MgO-incorporated hydrogel exhibits anti-swelling properties.The release of VCM from the hydrogel effectively kills S.aureus bacteria,with CMPMg-VCM(50)showing the highest antibacterial activity even after prolonged immersion in PBS solution for 12 days.Importantly,all the hydrogels are non-toxic to MC3T3-E1 cells and promote osteogenic differentiation through the early secretion of alkaline phosphatase and calcium nodule formation.Furthermore,in vivo experiments using a rat OM model reveal that the CMPMg-VCM hydrogel effectively kills and inhibits bacterial growth,while also protecting the infected bone from osteolysis.These beneficial properties are attributed to the burst release of VCM,which disrupts bacterial biofilm,as well as the release of Mg ions and hydroxyl by the degradation of MgO NPs,which inhibits bacterial growth and prevents osteolysis.Overall,the CMPMg-VCM hydrogel exhibits promising potential for the treatment of microbial bone infections.展开更多
Messenger RNA(mRNA)therapy is the intracellular delivery of mRNA to produce desired therapeutic proteins.Developing strategies for local mRNA delivery is still required where direct intra-articular injections are inap...Messenger RNA(mRNA)therapy is the intracellular delivery of mRNA to produce desired therapeutic proteins.Developing strategies for local mRNA delivery is still required where direct intra-articular injections are inappropriate for targeting a specific tissue.The mRNA delivery efficiency depends on protecting nucleic acids against nuclease-mediated degradation and safe site-specific intracellular delivery.Herein,novel mRNA-releasing matrices based on RGD-moiety-rich gelatin methacryloyl(GelMA)microporous annealed particle(MAP)scaffolds are reported.GelMA concentration in aerogel-based microgels(μgels)produced through a microfluidic process,MAP stiffnesses,and microporosity are crucial parameters for cell adhesion,spreading,and proliferation.After being loaded with mRNA complexes,MAP scaffolds composed of 10%GelMAμgels display excellent cell viability with increasing cell infiltration,adhesion,proliferation,and gene transfer.The intracellular delivery is achieved by the sustained release of mRNA complexes from MAP scaffolds and cell adhesion on mRNA-releasing scaffolds.These findings highlight that hybrid systems can achieve efficient protein expression by delivering mRNA complexes,making them promising mRNA-releasing biomaterials for tissue engineering.展开更多
基金supported by Natural Science Foundation of China(No.82202664,82172432,U22A20371)Shenzhen Sustainable Development Project(No.KCXFZ20201221173411031)+4 种基金Shenzhen Science and Technology Program(JCYJ20220818102815033,National Science Foundation of Guangdong Province(No.2021A1515220053,2022A1515010034,2021B1515120061)Guangdong Basic and Applied Basic Research Foundation(No.2019A1515110983,2022A1515012663)Guangzhou Basic and Applied Basic Research Foundation(202102021160)the Fundamental Research Funds for the Central Universities(21624221)the Research Fund Program of Guangdong Provincial Key Laboratory of Speed Capability Research(2023B1212010009).
文摘In clinical settings,regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods,restricted bone growth medications,and a scarcity of commercial bone grafts.To treat this life-threatening issue,improved biofunctional grafts capable of properly healing critical-sized bone defects are required.In this study,we effectively created anti-fracture hydrogel systems using spongy-like metal-organic(magnesium-phosphate)coordinated chitosan-modified injectable hydrogels(CPMg)loaded with a bioinspired neobavaisoflavone(NBF)component.The CPMg-NBF hydrogels showed outstanding anti-fracture capabilities during compression testing and retained exceptional mechanical stability even after 28 d of immersion in phosphatebuffered saline.They also demonstrated prolonged and stable release profiles of Mg^(2+)and NBF.Importantly,CPMg-NBF hydrogels revealed robust biphasic mineralization and were non-toxic to MC3T3-E1 cells.To better understand the underlying mechanism of Mg^(2+)and NBF component,as well as their synergistic effect on osteogenesis,we investigated the expression of key osteogenic proteins in the p38 MAPK and NOTCH pathways.Our results showed that CPMg-NBF hydrogels greatly increased the expression of osteogenic proteins(Runx2,OCN,OPN,BMPS and ALP).In vivo experiments showed that the implantation of CPMg-NBF hydrogels resulted in a significant increase in new bone growth within critical-sized calvarial defects.Based on these findings,we expect that the CPMg-NBF supramolecular hydrogel has tremendous promise for use as a therapeutic biomaterial for treating critical-sized calvarial defects.
基金Project(GJHZ20190822095418365)supported by Shenzhen International Cooperation Research,ChinaProject(2019011)supported by NTUT-SZU Joint Research Program,China+2 种基金Project(2019040)supported by Natural Science Foundation of Shenzhen University,ChinaProject(JCYJ20190808144009478)supported by Shenzhen Fundamental Research Fund,ChinaProject(ZDYBH201900000008)supported by Shenzhen Bureau of Industry and Information Technology,China。
文摘Selective laser melting(SLM)is an emerging layer-wise additive manufacturing technique that can generate complex components with high performance.Particulate-reinforced aluminum matrix composites(PAMCs)are important materials for various applications due to the combined properties of Al matrix and reinforcements.Considering the advantages of SLM technology and PAMCs,the novel SLM PAMCs have been developed and researched in recent years.Therefore,the current research progress about the SLM PAMCs is reviewed.Firstly,special attention is paid to the solidification behavior of SLM PAMCs.Secondly,the important issues about the design and fabrication of high-performance SLM PAMCs,including the selection of reinforcement,the influence of parameters on the processing and microstructure,the defect evolution and phase control,are highlighted and discussed comprehensively.Thirdly,the performance and strengthening mechanism of SLM PAMCs are systematically figured out.Finally,future directions are pointed out on the advancement of high-performance SLM PAMCs.
基金Project(2020A1515110869)supported by Guangdong Basic and Applied Basic Research Foundation,ChinaProject(GJHZ20190822095418365)supported by Shenzhen International Cooperation Research,China+3 种基金Project(51775351)supported by the National Natural Science Foundation of ChinaProject(2019011)supported by the NTUT-SZU Joint Research Program,ChinaProject(2019040)supported by the Natural Science Foundation of SZU,ChinaProject(ASTRA6-6)supported by the European Regional Development Fund,European Union。
文摘Ti-6Al-4V specimens were fabricated by selective laser melting(SLM)to study the effect of thermal treatment on the phase transformation,elemental diffusion,microstructure,and mechanical properties.The results show that vanadium enriches around the boundary ofαphases with increasing annealing temperature to 973 K,andα′phases transform intoα+βat 973 K.The typicalα′martensite microstructure transforms to fine-scale equiaxed microstructure at 973 K and the equiaxed microstructure significantly coarsens with increasing annealing temperature to 1273 K.The SLM Ti-6Al-4V alloy annealed at 973 K exhibits a well-balanced combination of strength and ductility((1305±25)MPa and(37±3)%,respectively).
基金This work was financially supported by the National Natural Science Foundation of China(Nos.11972202,51905279).
文摘High entropy alloys(HEAs)have recently received extensive attention due to their appealing mechani-cal performance given their simple phase formation.This study utilized laser powder bed fusion(LPBF)to fabricate high-performance HEA components.By processing respective powder blends,LPBF enabled the fabrication of stronger composites with a uniformly distributed reinforcing phase.Here,the impact of varying content of nano-scale TiC(1-3 wt%)particles for strengthening the CoCrFeMnNi HEA was ex-plored.The microstructural features and mechanical properties of the HEA composites were investigated in detail.The introduction of nano-scale TiC into the HEA matrix encouraged the development of cross-scale hierarchical microstructure and eliminated the formation of oxide inclusions.Incorporating more nano-TiC led to a higher dislocation density and more refined microstructure in the HEA composites,whereas it posed little influence on the anisotropy of the HEA matrix which typically featured a<001>texture along the building direction.With an optimized content of nano-TiC(1-2 wt%),the strength-ductility trade-offcan be overcome by exploiting multiple strengthening mechanisms encompassing grain boundary strengthening,solid solution strengthening,Orowan strengthening,and dislocation strengthen-ing.The HEA composites showed a favored strength-ductility combination with a yield strength of 748-882 MPa,ultimate tensile strength of 931-1081 MPa,and fracture elongation of 23%-29%.This study demonstrates that the introduction of nano-scale TiC is an effective way to simultaneously improve the strength and ductility of additively manufactured HEA materials.
基金the Guangdong Basic and Applied Basic Research Foundation(2020A1515110869)Shenzhen International Cooperation Research(GJHZ20190822095418365)+2 种基金the Natural Science Foundation of SZU(Grant No.2019040)Additional support was provided by the European Regional Development Fund(ASTRA6-6)Jürgen Eckert is grateful for the support from the Ministry of Science and Higher Education of the Russian Federation in the framework of the Increase Competitiveness Program of MISiS(Support project for young research engineers,Project No.K2-2020-046)。
文摘Al-7Si-0.5Mg-0.5Cu alloy specimens have been fabricated by selective laser melting(SLM).In this study,the effects of solution treatment,quenching,and artifi cial aging on the microstructural evolution,as well as mechanical and wear properties,have been investigated.The as-prepared samples show a heterogeneous cellular microstructure with two different cell sizes composed ofα-Al and Si phases.After solution-treated and quenched(SQ)heat treatment,the cellular microstructure disappears,and coarse and lumpy Si phase precipitates and a rectangular Cu-rich phase were observed.Subsequent aging after solution-treated and quenched(SQA)heat treatment causes the formation of nanosized Cu-rich precipitates.The asprepared SLMs sample has good mechanical properties and wear resistance(compressive yield strength:215±6 MPa and wear rate 2×10^(-13)m^(3)/m).The SQ samples with lumpy Si particles have the lowest strength of 167±13 MPa and the highest wear rate of 6.18×10^(1-13)m^(3)/m.The formation of nanosized Cu-rich precipitates in the SQA samples leads to the highest compressive yield strength of 233±6 MPa and a good wear rate of 5.06×10^(-13)m^(3)/m.
文摘Solar ultraviolet B(UVB)radiation is a major skin cancer-causing agent.Initiation,promotion,and progression are the diverse phases of UVB-induced carcinogenesis.Exposure to UVB causes abnormalities in a series of biochemical and molecular pathways:thymine dimer formation,DNA damage,oxidative stress,inflammatory responses,and altered cell signaling,eventually resulting in tumor formation.The increased skin cancer rates urge researchers to develop more efficient drugs,but synthetic chemotherapeutic drugs have more contrary effects and drug resistance issues,which have been reported recently.The current review focuses on the relationship between microbes and cancer.Human skin acts as a barrier against the external environment and serves as a protective shield for its inhabitant microbiota,collectively called skin microbes.The gut microbiome plays a vital role in cancer therapy.Production of short-chain fatty acids(SCFAs)such as butyrate,acetate,and propionate by intestinal microbes has anti-cancer properties against various cancer cell lines.Yet,the knowledge of SCFAs produced by skin microbes remains yet to be elucidated exhaustively.In this review,we strive to summarize the findings of studies performed to date regarding the anti-cancer properties of SCFA against various cancer cell lines and provide insight into future directions in the skin microbiome field.
基金funding from NSERC(RGPIN-2023-04460)CFI(No.36664)。
文摘The study explores the processing and characterization of dense tungsten carbide(WC)–10 wt.%nickel(Ni)structures(WC-10Ni)built using laser powder bed fusion(LPBF).LPBF experimental trials were conducted at different combinations of process parameters based on central composite design to develop process maps.Three samples built at different laser energy densities(LED of 460,381.7 and 300 J·m^(-3))with a 10 wt.%high relative density(>83.8%)were subjected to microstructural analysis,phase analysis,microhardness assessment,and abrasive wear testing.The characterizations focused on understanding the microstructure and mechanical behavior of LPBF-built WC-10Ni and developing a correlation between LED and material behavior.Higher LED resulted in keyhole porosity,while lower LED led to lack-of-fusion pores.The carbide particle size increased with LED,attributed to thermal cycling and coalescence during solidification.Higher LED also induced phase transformations,such as,the decomposition of WC into W_(2)C and the oxidation of Ni.Microhardness testing showed that the WC phase reached 1650 HV1,while the Ni matrix reached 1011 HV1.The abrasive wear testing demonstrated mass loss of<1%.Investigation of the wear scar resulted in the conclusion that the uniform distribution of WC particles in the Ni matrix contributed to this performance.The above studies indicate a positive correlation among relative density,hardness,and wear resistance.The study paves the way to understand the processing and material characteristics of LPBF-built WC-10Ni.
基金supported by the Natural Science Foundation of China(no.82202664)Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research(no.ZDSYS20220606100602005)+2 种基金Guangdong Basic and Applied Basic Research Foundation(no.2023A1515012764,2021A1515220053,2022A1515220038)Sichuan Science and Technology Program(2023ZYD0115)Shenzhen Science and Technology Project(JCYJ20190809165805604,JCYJ20220818102815033,JCYJ20220531094214032),and Shenzhen High-level Hospital Construction Fund.
文摘Microbial infections of bones,particularly after joint replacement surgery,are a common occurrence in clinical settings and often lead to osteomyelitis(OM).Unfortunately,current treatment approaches for OM are not satisfactory.To address this issue,this study focuses on the development and evaluation of an injectable magnesium oxide(MgO)nanoparticle(NP)-coordinated phosphocreatine-grafted chitosan hydrogel(CMPMg-VCM)loaded with varying amounts of vancomycin(VCM)for the treatment of OM.The results demonstrate that the loading of VCM does not affect the formation of the injectable hydrogel,and the MgO-incorporated hydrogel exhibits anti-swelling properties.The release of VCM from the hydrogel effectively kills S.aureus bacteria,with CMPMg-VCM(50)showing the highest antibacterial activity even after prolonged immersion in PBS solution for 12 days.Importantly,all the hydrogels are non-toxic to MC3T3-E1 cells and promote osteogenic differentiation through the early secretion of alkaline phosphatase and calcium nodule formation.Furthermore,in vivo experiments using a rat OM model reveal that the CMPMg-VCM hydrogel effectively kills and inhibits bacterial growth,while also protecting the infected bone from osteolysis.These beneficial properties are attributed to the burst release of VCM,which disrupts bacterial biofilm,as well as the release of Mg ions and hydroxyl by the degradation of MgO NPs,which inhibits bacterial growth and prevents osteolysis.Overall,the CMPMg-VCM hydrogel exhibits promising potential for the treatment of microbial bone infections.
基金National Institutes of Health,Grant/Award Numbers:HL140951,HL137193,CA257558,DK130566Ministry of Education,Grant/Award Number:RS-2023-00240729+3 种基金Korea University,Grant/Award Number:K2326671Coordenação de Aperfeiçoamento de Pessoal de Nível Superior,Grant/Award Numbers:2018/18523-3,2021/07057-4Fundação de AmparoàPesquisa do Estado de São Paulo,Grant/Award Numbers:2021/07057-4,2018/18523-3,2021/11564-9National Research Foundation of Korea,Grant/Award Number:RS-2023-00240729。
文摘Messenger RNA(mRNA)therapy is the intracellular delivery of mRNA to produce desired therapeutic proteins.Developing strategies for local mRNA delivery is still required where direct intra-articular injections are inappropriate for targeting a specific tissue.The mRNA delivery efficiency depends on protecting nucleic acids against nuclease-mediated degradation and safe site-specific intracellular delivery.Herein,novel mRNA-releasing matrices based on RGD-moiety-rich gelatin methacryloyl(GelMA)microporous annealed particle(MAP)scaffolds are reported.GelMA concentration in aerogel-based microgels(μgels)produced through a microfluidic process,MAP stiffnesses,and microporosity are crucial parameters for cell adhesion,spreading,and proliferation.After being loaded with mRNA complexes,MAP scaffolds composed of 10%GelMAμgels display excellent cell viability with increasing cell infiltration,adhesion,proliferation,and gene transfer.The intracellular delivery is achieved by the sustained release of mRNA complexes from MAP scaffolds and cell adhesion on mRNA-releasing scaffolds.These findings highlight that hybrid systems can achieve efficient protein expression by delivering mRNA complexes,making them promising mRNA-releasing biomaterials for tissue engineering.
