Nucleus pulposus(NP)tissue engineering brings new hope in the repair of intervertebral disc degeneration(IVDD).IVDD is often accompanied by multiscale changes in the mechanical microenvironment,including the changes o...Nucleus pulposus(NP)tissue engineering brings new hope in the repair of intervertebral disc degeneration(IVDD).IVDD is often accompanied by multiscale changes in the mechanical microenvironment,including the changes of mechanical property of collagen fibril,NP tissue,and mechanical instability of spine.In this study,a multiscale mechanically-adapted strategy is proposed to promote NP repair.To achieve this goal,a viscoelasticadapted dual-network hydrogel(PVA-DN)is constructed.The hydrogel with multiscale tunable viscoelasticity and dynamic compression condition is used to meet the multiscale mechanical requirements of NP regeneration.The results show that the viscoelastic hydrogel promotes the proliferation,migration and adhesion of nucleus pulposus cell(NPC)as well as the secretion of NP-specific extracellular matrix.RNA-seq results show that it attenuates the inflammatory microenvironment by inhibiting the IL-17 signaling pathway.Appropriate dynamic compression applied to the viscoelastic scaffold further promotes the physiological function of NPC,and the viscoelasticity of hydrogel protects against NPC damage induced by excessive compression.Animal experiments demonstrate that the viscoelastic hydrogel effectively restores disc mechanical function and delays disc degen-eration in rats.Findings from this study highlight that the multiscale mechanically-adapted strategy is effective in the repair of IVDD.展开更多
Cell sheet-based scaffold-free technology holds promise for tissue engineering applications and has been extensively explored during the past decades.However,efficient harvest and handling of cell sheets remain challe...Cell sheet-based scaffold-free technology holds promise for tissue engineering applications and has been extensively explored during the past decades.However,efficient harvest and handling of cell sheets remain challenging,including insufficient extracellular matrix content and poor mechanical strength.Mechanical loading has been widely used to enhance extracellular matrix production in a variety of cell types.However,currently,there are no effective ways to apply mechanical loading to cell sheets.In this study,we prepared thermo-responsive elastomer substrates by grafting poly(N-isopropyl acrylamide)(PNIPAAm)to poly(dimethylsiloxane)(PDMS)surfaces.The effect of PNIPAAm grafting yields on cell behaviours was investigated to optimize surfaces suitable for cell sheet culturing and harvesting.Subsequently,MC3T3-E1 cells were cultured on the PDMS-g-PNIPAAm substrates under mechanical stimulation by cyclically stretching the substrates.Upon maturation,the cell sheets were harvested by lowering the temperature.We found that the extracellular matrix content and thickness of cell sheet were markedly elevated upon appropriate mechanical conditioning.Reverse transcription quantitative polymerase chain reaction and Western blot analyses further confirmed that the expression of osteogenic-specific genes and major matrix components were up-regulated.After implantation into the critical-sized calvarial defects of mice,the mechanically conditioned cell sheets significantly promoted new bone formation.Findings from this study reveal that thermo-responsive elastomer,together with mechanical conditioning,can potentially be applied to prepare high-quality cell sheets for bone tissue engineering.展开更多
A biomechanical environment constructed exploiting the mechanical property of the extracellular matrix and external loading is essential for cell behaviour.Building suitable mechanical stimuli using feasible scaffold ...A biomechanical environment constructed exploiting the mechanical property of the extracellular matrix and external loading is essential for cell behaviour.Building suitable mechanical stimuli using feasible scaffold material and moderate mechanical loading is critical in bone tissue engineering for bone repair.However,the detailed mechanism of the mechanical regulation remains ambiguous.In addition,TRPV4 is involved in bone development.Therefore,this study aims to con-struct a viscoelastic hydrogel combined with dynamic compressive loading and investigate the effect of the dynamic mechanical envi-ronment on the osteogenic differentiation of stem cells and bone re-pair in vivo.The role of TRPV4 in the mechanobiology process was also assessed.A sodium alginate–gelatine hydrogel with adjustable viscoelasticity and good cell adhesion ability was obtained.The osteogenic differentiation of BMSCs was obtained using the fast stress relaxation hydrogel and a smaller compression strain of 1.5%.TRPV4 was activated in the hydrogel with fast stress relaxation time,followed by the increase in intracellular Ca^(2+)level and the activation of the Wnt/β-catenin pathway.The inhibition of TRPV4 induced a decrease in the intracellular Ca^(2+)level,down-regulation ofβ-catenin and reduced osteogenesis differentiation of BMSCs,suggesting that TRPV4 might be the key mechanism in the regulation of BMSC osteogenic differentiation in the viscoelastic dynamic mechanical environment.The fast stress re-laxation hydrogel also showed a good osteogenic promotion effect in the rat femoral defect model.The dynamic viscoelastic mechanical environment significantly induced the osteogenic differentiation of BMSCs and bone regeneration,which TRPV4 being involved in this mechanobiological process.Our study not only provided important guidance for the mechanical design of new biomaterials,but also provided a new perspective for the understanding of the interaction between cells and materials,the role of mechanical loading in tissue regeneration and the use of mechanical regulation in tissue engineering.展开更多
Addressing the challenge of eliminating bacteria and stimulating osteogenesis in infectious bone defects,where cells and bacteria coexist within the microenvironment,presents a significant hurdle.In this study,a strat...Addressing the challenge of eliminating bacteria and stimulating osteogenesis in infectious bone defects,where cells and bacteria coexist within the microenvironment,presents a significant hurdle.In this study,a strategy of targeting bacteria is proposed to address this challenge.For this purpose,a methacrylated gelatin composite hydrogel containing zinc ion and D-type cysteine-modified polydopamine nanoparticles(PZC)is developed.The D-cysteine,involved in the metabolism of the bacterial peptidoglycan chain,allows PZC to specifically target bacteria,exhibiting a form of“disguise strategy”.Through the targeting effect,this composite hydrogel can selectively kill bacteria and promote osteogenesis combing photothermal therapy with Zn^(2+)release,which showcases spatial controllability.Moreover,the antibacterial ability will be further improved after Near-infrared light irradiation.The multifunctional hydrogel containing Zn^(2+)modified nanoparticles can also promote osteogenic differentiation of bone marrow stem cells.Animal studies have revealed that the multifunctional hydrogel can inhibit bacteria growth and promote repair of infectious bone defects in rats.Findings from this study imply that endowing the nanoparticles with bacteria-targeting function can precisely control the events in cells and bacteria in the complex microenvironment,which can provide insights for the treatment of complex diseases with antibacterial requirements.展开更多
Bone is the second most commonly transplanted tissue worldwide,with over four million operations using bone grafts or bone substitute materials annually to treat bone defects.However,significant limitations affect cur...Bone is the second most commonly transplanted tissue worldwide,with over four million operations using bone grafts or bone substitute materials annually to treat bone defects.However,significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma,cancer,infection and arthritis.Developing bioactive three-dimensional(3D)scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering(BTE).A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts.However,individual groups of materials including polymers,ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone.Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds.This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers,hydrogels,metals,ceramics and bio-glasses in BTE.Scaffold fabrication methodology,mechanical performance,biocompatibility,bioactivity,and potential clinical translations will be discussed.展开更多
Annulus fibrosus(AF)repair remains a challenge because of its limited self-healing ability.Endogenous repair strategies combining scaffolds and growth factors show great promise in AF repair.Although the unique and be...Annulus fibrosus(AF)repair remains a challenge because of its limited self-healing ability.Endogenous repair strategies combining scaffolds and growth factors show great promise in AF repair.Although the unique and beneficial characteristics of decellularized extracellular matrix(ECM)in tissue repair have been demonstrated,the poor mechanical property of ECM hydrogels largely hinders their applications in tissue regeneration.In the present study,we combined polyethylene glycol diacrylate(PEGDA)and decellularized annulus fibrosus matrix(DAFM)to develop an injectable,photocurable hydrogel for AF repair.We found that the addition of PEGDA markedly improved the mechanical strength of DAFM hydrogels while maintaining their porous structure.Transforming growth factor-β1(TGF-β1)was further incorporated into PEGDA/DAFM hydrogels,and it could be continuously released from the hydrogel.The in vitro experiments showed that TGF-β1 facilitated the migration of AF cells.Furthermore,PEGDA/DAFM/TGF-β1 hydrogels supported the adhesion,proliferation,and increased ECM production of AF cells.In vivo repair performance of the hydrogels was assessed using a rat AF defect model.The results showed that the implantation of PEGDA/DAFM/TGF-β1 hydrogels effectively sealed the AF defect,prevented nucleus pulposus atrophy,retained disc height,and partially restored the biomechanical properties of disc.In addition,the implanted hydrogel was infiltrated by cells resembling AF cells and well integrated with adjacent AF tissue.In summary,findings from this study indicate that TGF-β1-supplemented DAFM hydrogels hold promise for AF repair.展开更多
The critical factor determining the in vivo effect of bone repair materials is the microenvironment,which greatly depends on their abilities to promote vascularization and bone formation.However,implant materials are ...The critical factor determining the in vivo effect of bone repair materials is the microenvironment,which greatly depends on their abilities to promote vascularization and bone formation.However,implant materials are far from ideal candidates for guiding bone regeneration due to their deficient angiogenic and osteogenic microenvironments.Herein,a double-network composite hydrogel combining vascular endothelial growth factor(VEGF)-mimetic peptide with hydroxyapatite(HA)precursor was developed to build an osteogenic microenvironment for bone repair.The hydrogel was prepared by mixing acrylatedβ-cyclodextrins and octacalcium phosphate(OCP),an HA precursor,with gelatin solution,followed by ultraviolet photo-crosslinking.To improve the angiogenic potential of the hydrogel,QK,a VEGF-mimicking peptide,was loaded in acrylatedβ-cyclodextrins.The QK-loaded hydrogel promoted tube formation of human umbilical vein endothelial cells and upregulated the expression of angiogenesis-related genes,such as Flt1,Kdr,and VEGF,in bone marrow mesenchymal stem cells.Moreover,QK could recruit bone marrow mesenchymal stem cells.Furthermore,OCP in the composite hydrogel could be transformed into HA and release calcium ions facilitating bone regeneration.The double-network composite hydrogel integrated QK and OCP showed obvious osteoinductive activity.The results of animal experiments showed that the composite hydrogel enhanced bone regeneration in skull defects of rats,due to perfect synergistic effects of QK and OCP on vascularized bone regeneration.In summary,improving the angiogenic and osteogenic microenvironments by our double-network composite hydrogel shows promising prospects for bone repair.展开更多
There is a high demand for bespoke grafts to replace damaged or malformed bone and cartilage tissue.Three-dimensional(3D)printing offers a method of fabricating complex anatomical features of clinically relevant sizes...There is a high demand for bespoke grafts to replace damaged or malformed bone and cartilage tissue.Three-dimensional(3D)printing offers a method of fabricating complex anatomical features of clinically relevant sizes.However,the construction of a scaffold to replicate the complex hierarchical structure of natural tissues remains challenging.This paper reports a novel biofabrication method that is capable of creating intricately designed structures of anatomically relevant dimensions.The beneficial properties of the electrospun fibre meshes can finally be realised in 3D rather than the current promising breakthroughs in two-dimensional(2D).The 3D model was created from commercially available computer-aided design software packages in order to slice the model down into many layers of slices,which were arrayed.These 2D slices with each layer of a defined pattern were laser cut,and then successfully assembled with varying thicknesses of 100μm or 200μm.It is demonstrated in this study that this new biofabrication technique can be used to reproduce very complex computer-aided design models into hierarchical constructs with micro and nano resolutions,where the clinically relevant sizes ranging from a simple cube of 20 mm dimension,to a more complex,50 mm-tall human ears were created.In-vitro cell-contact studies were also carried out to investigate the biocompatibility of this hierarchal structure.The cell viability on a micromachined electrospun polylactic-co-glycolic acid fibre mesh slice,where a range of hole diameters from 200μm to 500μm were laser cut in an array where cell confluence values of at least 85%were found at three weeks.Cells were also seeded onto a simpler stacked construct,albeit made with micromachined poly fibre mesh,where cells can be found to migrate through the stack better with collagen as bioadhesives.This new method for biofabricating hierarchical constructs can be further developed for tissue repair applications such as maxillofacial bone injury or nose/ear cartilage replacement in the future.展开更多
基金supported by the National Natural Science Foundation of China(32201070,32171350,32471410,32171321,81925027,32130059)Jiangsu Basic Research Program(Natural Science Founda-tion)(BK20240019,BK20240020)+3 种基金International Cooperation Project of Ningbo City(2023H013)Medical and Health Science and Technology Innovation Project of Suzhou(SKY2022105)Basic cutting-edge innovation cross project of Suzhou Medical College of Soochow University(YXY2302010)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Nucleus pulposus(NP)tissue engineering brings new hope in the repair of intervertebral disc degeneration(IVDD).IVDD is often accompanied by multiscale changes in the mechanical microenvironment,including the changes of mechanical property of collagen fibril,NP tissue,and mechanical instability of spine.In this study,a multiscale mechanically-adapted strategy is proposed to promote NP repair.To achieve this goal,a viscoelasticadapted dual-network hydrogel(PVA-DN)is constructed.The hydrogel with multiscale tunable viscoelasticity and dynamic compression condition is used to meet the multiscale mechanical requirements of NP regeneration.The results show that the viscoelastic hydrogel promotes the proliferation,migration and adhesion of nucleus pulposus cell(NPC)as well as the secretion of NP-specific extracellular matrix.RNA-seq results show that it attenuates the inflammatory microenvironment by inhibiting the IL-17 signaling pathway.Appropriate dynamic compression applied to the viscoelastic scaffold further promotes the physiological function of NPC,and the viscoelasticity of hydrogel protects against NPC damage induced by excessive compression.Animal experiments demonstrate that the viscoelastic hydrogel effectively restores disc mechanical function and delays disc degen-eration in rats.Findings from this study highlight that the multiscale mechanically-adapted strategy is effective in the repair of IVDD.
基金National Natural Science Foundation of China(No.81925027)Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Cell sheet-based scaffold-free technology holds promise for tissue engineering applications and has been extensively explored during the past decades.However,efficient harvest and handling of cell sheets remain challenging,including insufficient extracellular matrix content and poor mechanical strength.Mechanical loading has been widely used to enhance extracellular matrix production in a variety of cell types.However,currently,there are no effective ways to apply mechanical loading to cell sheets.In this study,we prepared thermo-responsive elastomer substrates by grafting poly(N-isopropyl acrylamide)(PNIPAAm)to poly(dimethylsiloxane)(PDMS)surfaces.The effect of PNIPAAm grafting yields on cell behaviours was investigated to optimize surfaces suitable for cell sheet culturing and harvesting.Subsequently,MC3T3-E1 cells were cultured on the PDMS-g-PNIPAAm substrates under mechanical stimulation by cyclically stretching the substrates.Upon maturation,the cell sheets were harvested by lowering the temperature.We found that the extracellular matrix content and thickness of cell sheet were markedly elevated upon appropriate mechanical conditioning.Reverse transcription quantitative polymerase chain reaction and Western blot analyses further confirmed that the expression of osteogenic-specific genes and major matrix components were up-regulated.After implantation into the critical-sized calvarial defects of mice,the mechanically conditioned cell sheets significantly promoted new bone formation.Findings from this study reveal that thermo-responsive elastomer,together with mechanical conditioning,can potentially be applied to prepare high-quality cell sheets for bone tissue engineering.
基金supported by the National Natural Science Foundation of China(32201070,32071307 and 32171350)International Cooperation Project of Ningbo City(2023H013)+2 种基金Medical and Health Science and Technology Innovation Project of Suzhou(SKY2022105)Basic Cutting-Edge Innovation Cross-Project of Suzhou Medical College of Soochow University(YXY2302010)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘A biomechanical environment constructed exploiting the mechanical property of the extracellular matrix and external loading is essential for cell behaviour.Building suitable mechanical stimuli using feasible scaffold material and moderate mechanical loading is critical in bone tissue engineering for bone repair.However,the detailed mechanism of the mechanical regulation remains ambiguous.In addition,TRPV4 is involved in bone development.Therefore,this study aims to con-struct a viscoelastic hydrogel combined with dynamic compressive loading and investigate the effect of the dynamic mechanical envi-ronment on the osteogenic differentiation of stem cells and bone re-pair in vivo.The role of TRPV4 in the mechanobiology process was also assessed.A sodium alginate–gelatine hydrogel with adjustable viscoelasticity and good cell adhesion ability was obtained.The osteogenic differentiation of BMSCs was obtained using the fast stress relaxation hydrogel and a smaller compression strain of 1.5%.TRPV4 was activated in the hydrogel with fast stress relaxation time,followed by the increase in intracellular Ca^(2+)level and the activation of the Wnt/β-catenin pathway.The inhibition of TRPV4 induced a decrease in the intracellular Ca^(2+)level,down-regulation ofβ-catenin and reduced osteogenesis differentiation of BMSCs,suggesting that TRPV4 might be the key mechanism in the regulation of BMSC osteogenic differentiation in the viscoelastic dynamic mechanical environment.The fast stress re-laxation hydrogel also showed a good osteogenic promotion effect in the rat femoral defect model.The dynamic viscoelastic mechanical environment significantly induced the osteogenic differentiation of BMSCs and bone regeneration,which TRPV4 being involved in this mechanobiological process.Our study not only provided important guidance for the mechanical design of new biomaterials,but also provided a new perspective for the understanding of the interaction between cells and materials,the role of mechanical loading in tissue regeneration and the use of mechanical regulation in tissue engineering.
基金funding provided for this study by the National Key R&D Program of China(2023YFB3810200,2023YFB3810201)the National Natural Science Foundation of China(81925027,32171350,32471410)+8 种基金International Cooperation Project of Ningbo City(2023H013)Jiangsu Basic Research Program(Natural Science Foundation)(BK20240020)Medical and Health Science and Technology Innovation Project of Suzhou(SKY2022105)Jiangsu Province Science and Technology Plan Special Fund(BE2022730)Postdoctoral Fellowship Program of CPSF(BX20230253,GZB20230505)Basic cutting-edge innovation cross project of Suzhou Medical College of Soochow University(YXY2302010,YXY2304046,YXY2304053)the China Postdoctoral Science Foundation under Grant Number 2023TQ0235Science and Technology Development Project of Suzhou(SGC202379,SZS2023043)the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions.
文摘Addressing the challenge of eliminating bacteria and stimulating osteogenesis in infectious bone defects,where cells and bacteria coexist within the microenvironment,presents a significant hurdle.In this study,a strategy of targeting bacteria is proposed to address this challenge.For this purpose,a methacrylated gelatin composite hydrogel containing zinc ion and D-type cysteine-modified polydopamine nanoparticles(PZC)is developed.The D-cysteine,involved in the metabolism of the bacterial peptidoglycan chain,allows PZC to specifically target bacteria,exhibiting a form of“disguise strategy”.Through the targeting effect,this composite hydrogel can selectively kill bacteria and promote osteogenesis combing photothermal therapy with Zn^(2+)release,which showcases spatial controllability.Moreover,the antibacterial ability will be further improved after Near-infrared light irradiation.The multifunctional hydrogel containing Zn^(2+)modified nanoparticles can also promote osteogenic differentiation of bone marrow stem cells.Animal studies have revealed that the multifunctional hydrogel can inhibit bacteria growth and promote repair of infectious bone defects in rats.Findings from this study imply that endowing the nanoparticles with bacteria-targeting function can precisely control the events in cells and bacteria in the complex microenvironment,which can provide insights for the treatment of complex diseases with antibacterial requirements.
文摘Bone is the second most commonly transplanted tissue worldwide,with over four million operations using bone grafts or bone substitute materials annually to treat bone defects.However,significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma,cancer,infection and arthritis.Developing bioactive three-dimensional(3D)scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering(BTE).A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts.However,individual groups of materials including polymers,ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone.Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds.This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers,hydrogels,metals,ceramics and bio-glasses in BTE.Scaffold fabrication methodology,mechanical performance,biocompatibility,bioactivity,and potential clinical translations will be discussed.
基金the funding provided for this study by the National Natural Science Foundation of China(81925027,32130059,31872748,32171350,32101103)Natural Science Foundation of Jiangsu Province(BK20200199)+1 种基金China Postdoctoral Science Foundation(2021M702412)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Annulus fibrosus(AF)repair remains a challenge because of its limited self-healing ability.Endogenous repair strategies combining scaffolds and growth factors show great promise in AF repair.Although the unique and beneficial characteristics of decellularized extracellular matrix(ECM)in tissue repair have been demonstrated,the poor mechanical property of ECM hydrogels largely hinders their applications in tissue regeneration.In the present study,we combined polyethylene glycol diacrylate(PEGDA)and decellularized annulus fibrosus matrix(DAFM)to develop an injectable,photocurable hydrogel for AF repair.We found that the addition of PEGDA markedly improved the mechanical strength of DAFM hydrogels while maintaining their porous structure.Transforming growth factor-β1(TGF-β1)was further incorporated into PEGDA/DAFM hydrogels,and it could be continuously released from the hydrogel.The in vitro experiments showed that TGF-β1 facilitated the migration of AF cells.Furthermore,PEGDA/DAFM/TGF-β1 hydrogels supported the adhesion,proliferation,and increased ECM production of AF cells.In vivo repair performance of the hydrogels was assessed using a rat AF defect model.The results showed that the implantation of PEGDA/DAFM/TGF-β1 hydrogels effectively sealed the AF defect,prevented nucleus pulposus atrophy,retained disc height,and partially restored the biomechanical properties of disc.In addition,the implanted hydrogel was infiltrated by cells resembling AF cells and well integrated with adjacent AF tissue.In summary,findings from this study indicate that TGF-β1-supplemented DAFM hydrogels hold promise for AF repair.
基金the National Natural Science Foundation of China(81925027,31872748,and 82111530157)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22_3232)+3 种基金the Royal Society(IEC\NSFC\201166)the General Research Funding from the Research Grants Council of Hong Kong(14202920)the Health and Medical Research Fund,the Food and Health Bureau,the Government of the Hong Kong Special Administrative Region(08190416)the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions.
文摘The critical factor determining the in vivo effect of bone repair materials is the microenvironment,which greatly depends on their abilities to promote vascularization and bone formation.However,implant materials are far from ideal candidates for guiding bone regeneration due to their deficient angiogenic and osteogenic microenvironments.Herein,a double-network composite hydrogel combining vascular endothelial growth factor(VEGF)-mimetic peptide with hydroxyapatite(HA)precursor was developed to build an osteogenic microenvironment for bone repair.The hydrogel was prepared by mixing acrylatedβ-cyclodextrins and octacalcium phosphate(OCP),an HA precursor,with gelatin solution,followed by ultraviolet photo-crosslinking.To improve the angiogenic potential of the hydrogel,QK,a VEGF-mimicking peptide,was loaded in acrylatedβ-cyclodextrins.The QK-loaded hydrogel promoted tube formation of human umbilical vein endothelial cells and upregulated the expression of angiogenesis-related genes,such as Flt1,Kdr,and VEGF,in bone marrow mesenchymal stem cells.Moreover,QK could recruit bone marrow mesenchymal stem cells.Furthermore,OCP in the composite hydrogel could be transformed into HA and release calcium ions facilitating bone regeneration.The double-network composite hydrogel integrated QK and OCP showed obvious osteoinductive activity.The results of animal experiments showed that the composite hydrogel enhanced bone regeneration in skull defects of rats,due to perfect synergistic effects of QK and OCP on vascularized bone regeneration.In summary,improving the angiogenic and osteogenic microenvironments by our double-network composite hydrogel shows promising prospects for bone repair.
基金The authors acknowledge the funding support from the EPSRC(Funding Reference Number EP/L015995/1&EP/W004860/1)the Royal Society(IEC\NSFC\201166)+1 种基金the National Natural Science Foundation of China(No.82111530157)the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions。
文摘There is a high demand for bespoke grafts to replace damaged or malformed bone and cartilage tissue.Three-dimensional(3D)printing offers a method of fabricating complex anatomical features of clinically relevant sizes.However,the construction of a scaffold to replicate the complex hierarchical structure of natural tissues remains challenging.This paper reports a novel biofabrication method that is capable of creating intricately designed structures of anatomically relevant dimensions.The beneficial properties of the electrospun fibre meshes can finally be realised in 3D rather than the current promising breakthroughs in two-dimensional(2D).The 3D model was created from commercially available computer-aided design software packages in order to slice the model down into many layers of slices,which were arrayed.These 2D slices with each layer of a defined pattern were laser cut,and then successfully assembled with varying thicknesses of 100μm or 200μm.It is demonstrated in this study that this new biofabrication technique can be used to reproduce very complex computer-aided design models into hierarchical constructs with micro and nano resolutions,where the clinically relevant sizes ranging from a simple cube of 20 mm dimension,to a more complex,50 mm-tall human ears were created.In-vitro cell-contact studies were also carried out to investigate the biocompatibility of this hierarchal structure.The cell viability on a micromachined electrospun polylactic-co-glycolic acid fibre mesh slice,where a range of hole diameters from 200μm to 500μm were laser cut in an array where cell confluence values of at least 85%were found at three weeks.Cells were also seeded onto a simpler stacked construct,albeit made with micromachined poly fibre mesh,where cells can be found to migrate through the stack better with collagen as bioadhesives.This new method for biofabricating hierarchical constructs can be further developed for tissue repair applications such as maxillofacial bone injury or nose/ear cartilage replacement in the future.
