Hierarchical porous structure,which include macropores,minor pores,and micropores in scaffolds,are essential in the multiple biological functions of bone repair and regeneration.In this study,patientcustomized calcium...Hierarchical porous structure,which include macropores,minor pores,and micropores in scaffolds,are essential in the multiple biological functions of bone repair and regeneration.In this study,patientcustomized calcium-deficient hydroxyapatite(CDHA)scaffolds with three-level hierarchical porous structure were fabricated by indirect 3D printing technology and particulate leaching method.The sacrificial template scaffolds were fabricated using a photo-curing 3D printer,which provided a prerequisite for the integral structure and interconnected macropores of CDHA scaffolds.Additionally,20 wt%pore former was incorporated into the slurry to enhance the content of smaller pores within the CDHA-2 scaffolds,and then the CDHA-2 scaffolds were sintered to remove the sacrificial template scaffolds and pore former.The obtained CDHA-2 scaffolds exhibited interconnected macropores(300-400μm),minor pores(∼10-100μm),and micropores(<10μm)distributed throughout the scaffolds,which could promote bone tissue ingrowth,increase surface roughness,and enhance protein adsorption of scaffolds.In vitro studies identified that CDHA-2 scaffolds had nanocrystal grains,high specific surface area,and outstanding protein adsorption capacity,which could provide a microenvironment for cell adhesion,spreading,and proliferation.In addition,the murine intramuscular implantation experiment suggested that CDHA-2 scaffolds exhibited excellent osteoinductivity and were superior to traditional BCP ceramics under conditions without the addition of live cells and exogenous growth factors.The rabbit calvarial defect repair results indicated that CDHA-2 scaffolds could enhance in situ bone regeneration.In conclusion,these findings demonstrated that the hierarchical porous structure of CDHA scaffolds was a pivotal factor in modulating osteoinductivity and bone regeneration,and CDHA-2 scaffolds were potential candidates for bone regeneration.展开更多
为精准、高效改善城市老旧小区居住环境品质,提高其防灾、减灾能力,提出一种基于云模型的老旧小区韧性评价体系。基于韧性理论,对所选老旧小区按照不同年代进行分组,通过实地调研,获得陕西省西安市30组具有代表性的老旧小区特征数据,参...为精准、高效改善城市老旧小区居住环境品质,提高其防灾、减灾能力,提出一种基于云模型的老旧小区韧性评价体系。基于韧性理论,对所选老旧小区按照不同年代进行分组,通过实地调研,获得陕西省西安市30组具有代表性的老旧小区特征数据,参考相关文献及相关专家建议,确定建筑韧性、设施韧性、环境韧性、人员韧性共计4个一级指标、9个二级指标、30个三级指标,构成老旧小区的评价指标体系。采用层次分析法(analytic hierarchy process,AHP)确定各指标的主观权重,采用熵权法(entropy weight method,EWN)和准则去除效果法(method based on the removal effects of criteria,MEREC)确定客观权重,采用组合赋权法确定最终权重,运用MATLAB构建了基于云模型的老旧小区韧性评价体系。基于此评价体系,选取西安市一老旧小区——万庆巷小区进行韧性评价,所得结果能够较准确地反映该小区韧性薄弱环节,表明所建评价体系具有一定的适用性与有效性。展开更多
The bone regenerative scaffold with the tailored degradation rate matching with the growth rate of the new bone is essential for adolescent bone repair.To satisfy these requirement,we proposed bone tissue scaffolds wi...The bone regenerative scaffold with the tailored degradation rate matching with the growth rate of the new bone is essential for adolescent bone repair.To satisfy these requirement,we proposed bone tissue scaffolds with controlled degradation rate using osteoinductive materials(Ca-P bioceramics),which is expected to present a controllable biodegradation rate for patients who need bone regeneration.Physicochemical properties,porosity,compressive strength and degradation properties of the scaffolds were studied.3D printed Ca-P scaffold(3DS),gas foaming Ca-P scaffold(FS)and autogenous bone(AB)were used in vivo for personalized beagle skull defect repair.Histological results indicated that the 3DS was highly vascularized and well combined with surrounding tissues.FS showed obvious newly formed bone tissues.AB showed the best repair effect,but it was found that AB scaffolds were partially absorbed and degraded.This study indicated that the 3D printed Ca-P bioceramics with tailored biodegradation rate is a promising candidate for personalized skull bone tissue reconstruction.展开更多
With the emergence of DNA nanotechnology in the 1980s, self-assembled DNA nanostructures have attracted considerable attention worldwide due to their inherent biocompatibility, unsurpassed programmability, and versati...With the emergence of DNA nanotechnology in the 1980s, self-assembled DNA nanostructures have attracted considerable attention worldwide due to their inherent biocompatibility, unsurpassed programmability, and versatile functions. Especially promising nanostructures are tetrahedral framework nucleic acids(t FNAs), first proposed by Turberfield with the use of a one-step annealing approach. Benefiting from their various merits, such as simple synthesis, high reproducibility, structural stability, cellular internalization, tissue permeability, and editable functionality, t FNAs have been widely applied in the biomedical field as threedimensional DNA nanomaterials. Surprisingly, t FNAs exhibit positive effects on cellular biological behaviors and tissue regeneration,which may be used to treat inflammatory and degenerative diseases. According to their intended application and carrying capacity,t FNAs could carry functional nucleic acids or therapeutic molecules through extended sequences, sticky-end hybridization,intercalation, and encapsulation based on the Watson and Crick principle. Additionally, dynamic t FNAs also have potential applications in controlled and targeted therapies. This review summarized the latest progress in pure/modified/dynamic t FNAs and demonstrated their regenerative medicine applications. These applications include promoting the regeneration of the bone,cartilage, nerve, skin, vasculature, or muscle and treating diseases such as bone defects, neurological disorders, joint-related inflammatory diseases, periodontitis, and immune diseases.展开更多
At present,the clinical reconstruction of the auricle usually adopts the strategy of taking autologous costal cartilage.This method has great trauma to patients,poor plasticity and inaccurate shaping.Three-dimensional...At present,the clinical reconstruction of the auricle usually adopts the strategy of taking autologous costal cartilage.This method has great trauma to patients,poor plasticity and inaccurate shaping.Three-dimensional(3D)printing technology has made a great breakthrough in the clinical application of orthopedic implants.This study explored the combination of 3D printing and tissue engineering to precisely reconstruct the auricle.First,a polylactic acid(PLA)polymer scaffold with a precisely customized patient appearance was fabricated,and then auricle cartilage fragments were loaded into the 3D-printed porous PLA scaffold to promote auricle reconstruction.In vitro,gelatin methacrylamide(GelMA)hydrogels loaded with different sizes of rabbit ear cartilage fragments were studied to assess the regenerative activity of various autologous cartilage fragments.In vivo,rat ear cartilage fragments were placed in an accurately designed porous PLA polymer ear scaffold to promote auricle reconstruction.The results indicated that the chondrocytes in the cartilage fragments could maintain the morphological phenotype in vitro.After three months of implantation observation,it was conducive to promoting the subsequent regeneration of cartilage in vivo.The autologous cartilage fragments combined with 3D printing technology show promising potential in auricle reconstruction.展开更多
Chinese president Xi Jinping made clear at the National Health and Wellness Conference that health is the prerequisite for people’s all-around development and a precondition for the sustainable development of China. ...Chinese president Xi Jinping made clear at the National Health and Wellness Conference that health is the prerequisite for people’s all-around development and a precondition for the sustainable development of China. Oral health is an indispensable component of overall health in humans. However, the long neglect of oral health in overall health agendas has made oral diseases an increasing concern. With this perspective, we described the global challenges of oral diseases, with an emphasis on the challenges faced by China. We also described and analyzed the recently released health policies of the Chinese government, which aim to guide midterm and long-term oral health promotion in China. More importantly, we called for specific actions to fulfill the larger goal of oral health for the nation. The implementation of primordial prevention efforts against oral diseases, the integration of oral health into the promotion of overall health, and the management of oral diseases in conjunction with other chronic non-communicable diseases with shared risk factors were highly recommended. In addition, we suggested the reform of standard clinical residency training, the development of domestic manufacturing of dental equipment and materials, the revitalization traditional Chinese medicine for the prevention and treatment of oral diseases, and integration of oral health promotion into the Belt and Road Initiative. We look forward to seeing a joint effort from all aspects of the society to fulfill the goal of Healthy China 2030 and ensure the oral health of the nation.展开更多
The fast development of both biomaterials and regulatory science calls for a convergence,which is addressed in this article via their link through medical products of biomaterials and related safety and efficacy evalu...The fast development of both biomaterials and regulatory science calls for a convergence,which is addressed in this article via their link through medical products of biomaterials and related safety and efficacy evaluation.The updated definition of biomaterials,and concepts of biomaterials-related medical products and so-called medical-grade and implantable materials are firstly introduced.Then a brief overview of the concept and history of regulatory science and its assessment of safety and efficacy of medical products,as well as the currently ongoing biomaterials-related regulatory science programs are presented.Finally,the opportunities provided by regulatory science for biomaterials as well as challenges on how to develop a biomaterials-based regulatory science system are discussed.As the first article in the field to elucidate the relationship between biomaterials and regulatory science,key take-home messages include(1)biomaterials alone are not medical products;(2)regulatory authorities approve/clear final medical products,not biomaterials;(3)there is no definition/regulation on the so-called medical-grade or implantable materials;and(4)safety and efficacy refer to final medical products,not biomaterials alone.展开更多
Introduction and research overview Recently,increasing need for organ transplantation and lack of donated organs have led to the rapid development of new technologies for artificial organ biofabrication.In the era of ...Introduction and research overview Recently,increasing need for organ transplantation and lack of donated organs have led to the rapid development of new technologies for artificial organ biofabrication.In the era of burgeoning breakthroughs around 3D bioprinting technologies,the personalization of organs and medicine is an ongoing nice vision[1–5].As one of the leading laboratories in the interdisciplinary field of materials,manufacturing and bioengineering,the Biofabrication(3D Bioprinting)Research Laboratory at Sichuan University has been engaging in the research on customized regenerativemedicine since 2012.展开更多
Biofabrication,also known as bioprinting,has been widely used in the field of biomedicine.The three most important factors in biofabrication are 3D bioprinter,biomaterials to be printed(bioinks),and the printing objec...Biofabrication,also known as bioprinting,has been widely used in the field of biomedicine.The three most important factors in biofabrication are 3D bioprinter,biomaterials to be printed(bioinks),and the printing object(application).This review provides a detailed introduction to the latest research progress in these aspects.In particularly,the bioinks for bioprinting require strict biocompatible requirements.Four typical materials,i.e.metal/alloys,ceramics,polymers,and their composites,were introduced in detail,and their printing process and application scenarios were summarized,respectively.There are many applications of biofabrication in clinical practice.The application of biofabrication in skeletal system,skin and soft tissue,cardiovascular system,digestive system,respiratory system,urinary system,nervous system,plastic surgery and medical aesthetics were briefly introduced.The applications of biofabrication has a wide range of clinical need.Biofabrication is an innovative technology that is expected to further promote the clinical precision treatments.展开更多
Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis(OA),but directly modulating mitochondria in vivo remains a significant challenge.This study is the first to verify a correlation b...Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis(OA),but directly modulating mitochondria in vivo remains a significant challenge.This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients,highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA.Consequently,we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool(FoxO3)and integrated it within a nanoengineered‘truck’(NETT,FoxO3--NETT).This was further encapsulated in injectable hydrogel microspheres(FoxO3-NETT@SMs)to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes.Collectively,these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway.As a result,FoxO3-NETT@SMs stimulate chondrocytes proliferation,migration,and ECM production in vitro,and effectively alleviate OA progression in vivo,demonstrating significant potential for clinical applications.展开更多
Bioactive ceramics have been used in bone tissue repair and regeneration.However,because of the complex in vivo osteogenesis process,long cycle,and difficulty of accurately tracking,the mechanism of interaction betwee...Bioactive ceramics have been used in bone tissue repair and regeneration.However,because of the complex in vivo osteogenesis process,long cycle,and difficulty of accurately tracking,the mechanism of interaction between materials and cells has yet to be fully understood,hindering its development.The ceramic microbridge micro-fluidic chip system may solve the problem and provide an in vitro method to simulate the microenvironment in vivo.Nevertheless,the complex microenvironment parameters of the chip system need to be studied in detail.Computer simulation bionics can provide clues for the setting of microenvironment parameters.This study used a computational bionic model to simulate the bone growth process in the presence of immune-related factors.The osteoblast differentiation of mesenchymal stem cells of calcium phosphate ceramics in a macrophage-dominated immune microenvironment was studied using a microfluidic chip system.The computational biomimetic model and microfluidic chip findings were basically consistent with the reported results of the animal experiments.These findings suggest that studying the osteogenic behavior of calcium phosphate ceramics using a microfluidic chip model is feasible.The method model provided in this study can be extended to other biomaterials,providing a viable path for their research and evaluation.展开更多
The interior environment of articular cartilage in osteoarthritis(OA)presents substantial hurdles,leading to the malfunctionof chondrocytes and the breakdown of collagen II-enriched hyaline cartilage matrix.Despite th...The interior environment of articular cartilage in osteoarthritis(OA)presents substantial hurdles,leading to the malfunctionof chondrocytes and the breakdown of collagen II-enriched hyaline cartilage matrix.Despite this,mostclinical treatments primarily provide temporary relief from OA discomfort without arresting OA progression.This studyaimed to alleviate OA by developing intra-articular injectable dECM-enhanced hyaluronic(HE)microgels.The HEhydrogel was engineered and shaped into uniformly sized microgels using microfluidics and photopolymerizationtechniques.These microgels provided a spatiotemporal cascade effect,facilitating the rapid release of growth factorsand a slower release of ECM macromolecules and proteins.This process assisted in the recovery of OA chondrocytes’function,promoting cell proliferation,matrix synthesis,and cartilage-specific gene expression in vitro.It also effectivelyaided repair of the collagen II-enriched hyaline cartilage and significantly reduced the severity of OA,as demonstratedby radiological observation,gross appearance,histological/immunohistochemical staining,and analysisin an OA rat model in vivo.Collectively,the HE injectable microgels with spatiotemporal release of cartilage-specificmolecules have shown promise as a potential candidate for a cell-free OA therapy approach.展开更多
Collagen, recognized as the primary structural component of human skin, is essential for preserving dermal integrity and function. Its progressive depletion has been closely associated with structural deterioration of...Collagen, recognized as the primary structural component of human skin, is essential for preserving dermal integrity and function. Its progressive depletion has been closely associated with structural deterioration of the dermis and the visible signs of skin aging. Among current therapeutic strategies, the injection of exogenous collagen has been established as an effective method for alleviating aging-related skin changes. In the present study, a comprehensive evaluation was conducted to assess the injectability, cellular interactions, and photoaging repair efficacy of recombinant human collagen type III(RHC). The RHC solution was found to demonstrate favorable injectability and support the adhesion and chemotactic behavior of L929 cells, while also upregulating the expression of type I and type III collagen. In co-culture systems with lipopolysaccharide-stimulated macrophages, RHC treatment suppressed macrophage proliferation and reduced the production of proinflammatory cytokines, suggesting notable immunomodulatory properties. Upon intradermal injection of RHC into photoaged rat skin, an increased density of dermal collagen fibers was observed, accompanied by a more organized and uniform fiber arrangement. Additionally, hydroxyproline content and the expressions of collagen I and III were markedly elevated in the RHC group compared with the control and hyaluronic acid groups. Collectively, these findings suggest that RHC holds considerable promise as a therapeutic agent for both medical and cosmetic purposes targeting the restoration and maintenance of youthful skin characteristics.展开更多
Repair and reconstruction of large bone defect were often difficult,and bone substitute materials,including autogenous bone,allogenic bone and artificial bone,were common treatment strategies.The key to elucidate the ...Repair and reconstruction of large bone defect were often difficult,and bone substitute materials,including autogenous bone,allogenic bone and artificial bone,were common treatment strategies.The key to elucidate the clinical effect of these bone repair materials was to study their osteogenic capacity and immunotoxicological compatibility.In this paper,the mechanical properties,micro-CT imaging analysis,digital image analysis and histological slice analysis of the three bone grafts were investigated and compared after different time points of implantation in rat femur defect model.Autogenous bone and biphasic calcium phosphate particular artificial bone containing 61.4% HA and 38.6%β-tricalcium phosphate with 61.64%porosity and 0.8617±0.0068 g/cm^(3) den-sity(d≤2 mm)had similar and strong bone repair ability,but autogenous bone implant materials caused greater secondary damage to experimental animals;allogenic bone exhibited poor bone defect repair ability.At the early stage of implantation,the immunological indexes such as Immunoglobulin G,Immunoglobulin M concentration and CD4 cells'population of allogenic bone significantly increased in compared with those of autologous bone and artificial bone.Although the repair process of artificial bone was relatively inefficient than autologous bone graft,the low immunotoxicological indexes and acceptable therapeutic effects endowed it as an excellent alter-native material to solve the problems with insufficient source and secondary trauma of autogenous bone.展开更多
Osteoinductivity of porous calcium phosphate(CaP)ceramics has been widely investigated and confirmed,and it might be attributed to the rapid formation of the vascular networks after in vivo implantation of the ceramic...Osteoinductivity of porous calcium phosphate(CaP)ceramics has been widely investigated and confirmed,and it might be attributed to the rapid formation of the vascular networks after in vivo implantation of the ceramics.In this study,to explore the vascularization mechanism within the CaP ceramics,the migration and differentiation of bone marrow-derived mesenchymal stem cells(BMSCs)under the stimulation of porous biphasic calcium phosphate(BCP)ceramic with excellent osteoinductivity were systematically investigated.The results indicated that the directional migration of BMSCs toward BCP ceramic occurred when evaluated by using a transwell model,and the BMSCs migration was enhanced by the seeded macrophages on the ceramic in advance.Besides,by directly culturing BMSCs on BCP ceramic discs under both in vitro and in vivo physiological environment,it was found that the differentiation of BMSCs toward vascular endothelial cells(VECs)happened under the stimulation of BCP ceramic,as was confirmed by the up-regulated gene expressions and protein secretions of VECs-related characteristic factors,including kinase insert domain receptor,von willebrand factor,vascular cell adhesion molecule-1 and cadherin 5 in the BMSCs.This study offered a possibility for explaining the origin of VECs during the rapid vascularization process after in vivo implantation of porous CaP ceramics and could give some useful guidance to reveal the vascularization mechanism of the ceramics.展开更多
Supramolecular nanofiber peptide assemblies had been used to construct functional hydrogel biomaterials and achieved great progress.Here,a new class of biphenyl-tripeptides with different C-terminal amino acids sequen...Supramolecular nanofiber peptide assemblies had been used to construct functional hydrogel biomaterials and achieved great progress.Here,a new class of biphenyl-tripeptides with different C-terminal amino acids sequences transposition were developed,which could self-assemble to form robust supramolecular nanofiber hydrogels from 0.7 to 13.8 kPa at ultra-low weight percent(about 0.27 wt%).Using molecular dynamics simulations to interrogate the physicochemical properties of designed biphenyl-tripeptide sequences in atomic detail,reasonable hydrogen bond interactions and“FF”brick(phenylalanine-phenylalanine)promoted the formation of supramolecular fibrous hydrogels.The biomechanical properties and intermolecular interactions were also analyzed by rheology and spectroscopy analysis to optimize amino acid sequence.Enhanced L929 cells adhesion and proliferation demonstrated good biocompatibility of the hydrogels.The storage modulus of BPAA-AFF with 10 nm nanofibers self-assembling was around 13.8 kPa,and the morphology was similar to natural extracellular matrix.These supramolecular nanofiber hydrogels could effectively support chondrocytes spreading and proliferation,and specifically enhance chondrogenic related genes expression and chondrogenic matrix secretion.Such biomimetic supramolecular short peptide biomaterials hold great potential in regenerative medicine as promising innovative matrices because of their simple and regular molecular structure and excellent biological performance.展开更多
Collagen is a promising material for tissue engineering,but the poor mechanical properties of collagen hydrogels,which tend to cause contraction under the action of cellular activity,make its application challengeable...Collagen is a promising material for tissue engineering,but the poor mechanical properties of collagen hydrogels,which tend to cause contraction under the action of cellular activity,make its application challengeable.In this study,the amino group of type I collagen(Col I)was modified with methacrylic anhydride(MA)and the photo-crosslinkable methacrylate anhydride modified type I collagen(CM)with three different degrees of substitution(DS)was prepared.The physical properties of CM and Col I hydrogels were tested,including micromorphology,mechanical properties and degradation properties.The results showed that the storage modulus and degradation rate of hydrogels could be adjusted by changing the DS of CM.In vitro,chondrocytes were seeded into these four groups of hydrogels and subjected to fluorescein diacetate/propidium iodide(FDA/PI)staining,cell counting kit-8(CCK-8)test,histological staining and cartilage-related gene expression analysis.In vivo,these hydrogels encapsulating chondrocytes were implanted subcutaneously into nude mice,then histological staining and sulfated glycosaminoglycan(sGAG)/DNA assays were performed.The results demonstrated that contraction of hydrogels affected behaviors of chondrocytes,and CM hydrogels with suitable DS could resist contraction of hydrogels and promote the secretion of cartilage-specific matrix in vitro and in vivo.展开更多
In tissue engineering,bioactive materials play an important role,providing structural support,cell regulation and establishing a suitable microenvironment to promote tissue regeneration.As the main component of extrac...In tissue engineering,bioactive materials play an important role,providing structural support,cell regulation and establishing a suitable microenvironment to promote tissue regeneration.As the main component of extracellular matrix,collagen is an important natural bioactive material and it has been widely used in scientific research and clinical applications.Collagen is available from a wide range of animal origin,it can be produced by synthesis or through recombinant protein production systems.The use of pure collagen has inherent disadvantages in terms of physico-chemical properties.For this reason,a processed collagen in different ways can better match the specific requirements as biomaterial for tissue repair.Here,collagen may be used in bone/cartilage regeneration,skin regeneration,cardiovascular repair and other fields,by following different processing methods,including cross-linked collagen,complex,structured collagen,mineralized collagen,carrier and other forms,promoting the development of tissue engineering.This review summarizes a wide range of applications of collagen-based biomaterials and their recent progress in several tissue regeneration fields.Furthermore,the application prospect of bioactive materials based on collagen was outlooked,aiming at inspiring more new progress and advancements in tissue engineering research.展开更多
Extracellular matrix(ECM)-based biomaterials are promising candidates in cartilage tissue engineering by simulating the native microenvironment to regulate the chondrogenic differentiation of bone marrow mesenchymal s...Extracellular matrix(ECM)-based biomaterials are promising candidates in cartilage tissue engineering by simulating the native microenvironment to regulate the chondrogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)without exogenous growth factors.The biological properties of ECM scaffolds are primarily depended on the original source,which would directly influence the chondrogenic effects of the ECM materials.Despite the expanding investigations on ECM scaffolds in recent years,the selection of optimized ECM materials in cartilage regeneration was less reported.In this study,we harvested and compared the articular cartilage ECM from newborn,juvenile and adult rabbits.The results demonstrated the significant differences in the mechanical strength,sulphated glycosaminoglycan and collagen contents of the different aged ECM,before and after decellularization.Consequently,different compositional and mechanical properties were shown in the three ECM-based collagen hydrogels,which exerted age-dependent chondrogenic inducibility.In general,both in vitro and in vivo results suggested that the newborn ECM promoted the most chondrogenesis of BMSCs but led to severe matrix calcification.In contrast,BMSCs synthesized the lowest amount of cartilaginous matrix with minimal calcification with adult ECM.The juvenile ECM achieved the best overall results in promoting chondrogenesis of BMSCs and preventing matrix calcification.Together,this study provides important information to our current knowledge in the design of future ECM-based biomaterials towards a successful repair of articular cartilage.展开更多
基金supported by the National Key Research and Development Program of China(No.2019YFA0110600)the Science and Technology Support Program of Sichuan Province(No.2019YJ0161).
文摘Hierarchical porous structure,which include macropores,minor pores,and micropores in scaffolds,are essential in the multiple biological functions of bone repair and regeneration.In this study,patientcustomized calcium-deficient hydroxyapatite(CDHA)scaffolds with three-level hierarchical porous structure were fabricated by indirect 3D printing technology and particulate leaching method.The sacrificial template scaffolds were fabricated using a photo-curing 3D printer,which provided a prerequisite for the integral structure and interconnected macropores of CDHA scaffolds.Additionally,20 wt%pore former was incorporated into the slurry to enhance the content of smaller pores within the CDHA-2 scaffolds,and then the CDHA-2 scaffolds were sintered to remove the sacrificial template scaffolds and pore former.The obtained CDHA-2 scaffolds exhibited interconnected macropores(300-400μm),minor pores(∼10-100μm),and micropores(<10μm)distributed throughout the scaffolds,which could promote bone tissue ingrowth,increase surface roughness,and enhance protein adsorption of scaffolds.In vitro studies identified that CDHA-2 scaffolds had nanocrystal grains,high specific surface area,and outstanding protein adsorption capacity,which could provide a microenvironment for cell adhesion,spreading,and proliferation.In addition,the murine intramuscular implantation experiment suggested that CDHA-2 scaffolds exhibited excellent osteoinductivity and were superior to traditional BCP ceramics under conditions without the addition of live cells and exogenous growth factors.The rabbit calvarial defect repair results indicated that CDHA-2 scaffolds could enhance in situ bone regeneration.In conclusion,these findings demonstrated that the hierarchical porous structure of CDHA scaffolds was a pivotal factor in modulating osteoinductivity and bone regeneration,and CDHA-2 scaffolds were potential candidates for bone regeneration.
文摘为精准、高效改善城市老旧小区居住环境品质,提高其防灾、减灾能力,提出一种基于云模型的老旧小区韧性评价体系。基于韧性理论,对所选老旧小区按照不同年代进行分组,通过实地调研,获得陕西省西安市30组具有代表性的老旧小区特征数据,参考相关文献及相关专家建议,确定建筑韧性、设施韧性、环境韧性、人员韧性共计4个一级指标、9个二级指标、30个三级指标,构成老旧小区的评价指标体系。采用层次分析法(analytic hierarchy process,AHP)确定各指标的主观权重,采用熵权法(entropy weight method,EWN)和准则去除效果法(method based on the removal effects of criteria,MEREC)确定客观权重,采用组合赋权法确定最终权重,运用MATLAB构建了基于云模型的老旧小区韧性评价体系。基于此评价体系,选取西安市一老旧小区——万庆巷小区进行韧性评价,所得结果能够较准确地反映该小区韧性薄弱环节,表明所建评价体系具有一定的适用性与有效性。
基金This work was supported by the National Key Research and Development Program of China(No.18YFB1105600,2018YFC1106800)National Natural Science Foundation of China(51875518)+1 种基金Sichuan Province Science&Technology Department Projects(2016CZYD0004,2017SZ0001,2018GZ0142,2019YFH0079)Research Foundation for Young Teachers of Sichuan University(2018SCUH0017)and The“111”Project(No.B16033).
文摘The bone regenerative scaffold with the tailored degradation rate matching with the growth rate of the new bone is essential for adolescent bone repair.To satisfy these requirement,we proposed bone tissue scaffolds with controlled degradation rate using osteoinductive materials(Ca-P bioceramics),which is expected to present a controllable biodegradation rate for patients who need bone regeneration.Physicochemical properties,porosity,compressive strength and degradation properties of the scaffolds were studied.3D printed Ca-P scaffold(3DS),gas foaming Ca-P scaffold(FS)and autogenous bone(AB)were used in vivo for personalized beagle skull defect repair.Histological results indicated that the 3DS was highly vascularized and well combined with surrounding tissues.FS showed obvious newly formed bone tissues.AB showed the best repair effect,but it was found that AB scaffolds were partially absorbed and degraded.This study indicated that the 3D printed Ca-P bioceramics with tailored biodegradation rate is a promising candidate for personalized skull bone tissue reconstruction.
基金supported by National Key R&D Program of China(2019YFA0110600)National Natural Science Foundation of China(82101077,81970916)+3 种基金Sichuan Province Youth Science and Technology Innovation Team(2022JDTD0021)Sichuan University Postdoctoral Interdisciplinary Innovation Fundthe Fundamental Research Funds for the Central Universities,Postdoctoral Science Foundation of China(Grant 2021M692271)West China School/Hospital of Stomatology Sichuan University(No.RCDWJS2022-14 and RCDWJS2021-20)。
文摘With the emergence of DNA nanotechnology in the 1980s, self-assembled DNA nanostructures have attracted considerable attention worldwide due to their inherent biocompatibility, unsurpassed programmability, and versatile functions. Especially promising nanostructures are tetrahedral framework nucleic acids(t FNAs), first proposed by Turberfield with the use of a one-step annealing approach. Benefiting from their various merits, such as simple synthesis, high reproducibility, structural stability, cellular internalization, tissue permeability, and editable functionality, t FNAs have been widely applied in the biomedical field as threedimensional DNA nanomaterials. Surprisingly, t FNAs exhibit positive effects on cellular biological behaviors and tissue regeneration,which may be used to treat inflammatory and degenerative diseases. According to their intended application and carrying capacity,t FNAs could carry functional nucleic acids or therapeutic molecules through extended sequences, sticky-end hybridization,intercalation, and encapsulation based on the Watson and Crick principle. Additionally, dynamic t FNAs also have potential applications in controlled and targeted therapies. This review summarized the latest progress in pure/modified/dynamic t FNAs and demonstrated their regenerative medicine applications. These applications include promoting the regeneration of the bone,cartilage, nerve, skin, vasculature, or muscle and treating diseases such as bone defects, neurological disorders, joint-related inflammatory diseases, periodontitis, and immune diseases.
基金supported by the National Natural Science Foundation of China(No.81171731)the Project of Chengdu Science and Technology Bureau(Nos.2021-YF05-01619-SN and 2021-RC05-00022-CG)+2 种基金the Science and Technology Project of Tibet Autonomous Region(Nos.XZ202202YD0013C and XZ201901-GB-08)the Sichuan Science and Technology Program(No.2022YFG0066)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(Nos.ZYJC21026,ZYGD21001 and ZYJC21077).
文摘At present,the clinical reconstruction of the auricle usually adopts the strategy of taking autologous costal cartilage.This method has great trauma to patients,poor plasticity and inaccurate shaping.Three-dimensional(3D)printing technology has made a great breakthrough in the clinical application of orthopedic implants.This study explored the combination of 3D printing and tissue engineering to precisely reconstruct the auricle.First,a polylactic acid(PLA)polymer scaffold with a precisely customized patient appearance was fabricated,and then auricle cartilage fragments were loaded into the 3D-printed porous PLA scaffold to promote auricle reconstruction.In vitro,gelatin methacrylamide(GelMA)hydrogels loaded with different sizes of rabbit ear cartilage fragments were studied to assess the regenerative activity of various autologous cartilage fragments.In vivo,rat ear cartilage fragments were placed in an accurately designed porous PLA polymer ear scaffold to promote auricle reconstruction.The results indicated that the chondrocytes in the cartilage fragments could maintain the morphological phenotype in vitro.After three months of implantation observation,it was conducive to promoting the subsequent regeneration of cartilage in vivo.The autologous cartilage fragments combined with 3D printing technology show promising potential in auricle reconstruction.
基金supported by the National Natural Science Foundation of China (81771099 to XX, 81670978 to XZ)a Health Promotion Foundation grant from Chengdu City Government (2014-HM02-00041-SF)
文摘Chinese president Xi Jinping made clear at the National Health and Wellness Conference that health is the prerequisite for people’s all-around development and a precondition for the sustainable development of China. Oral health is an indispensable component of overall health in humans. However, the long neglect of oral health in overall health agendas has made oral diseases an increasing concern. With this perspective, we described the global challenges of oral diseases, with an emphasis on the challenges faced by China. We also described and analyzed the recently released health policies of the Chinese government, which aim to guide midterm and long-term oral health promotion in China. More importantly, we called for specific actions to fulfill the larger goal of oral health for the nation. The implementation of primordial prevention efforts against oral diseases, the integration of oral health into the promotion of overall health, and the management of oral diseases in conjunction with other chronic non-communicable diseases with shared risk factors were highly recommended. In addition, we suggested the reform of standard clinical residency training, the development of domestic manufacturing of dental equipment and materials, the revitalization traditional Chinese medicine for the prevention and treatment of oral diseases, and integration of oral health promotion into the Belt and Road Initiative. We look forward to seeing a joint effort from all aspects of the society to fulfill the goal of Healthy China 2030 and ensure the oral health of the nation.
基金financially supported by the Sichuan Science and Technology Program(No.2021YFS0020)the Natural Science Foundation of China(No.32001002)supported by the second batch(“3.1 Investigating technologies of assessing the safety and effectiveness of nano-medical device products”,“5.3 Investigating innovative supervision and assessment technologies of tissue engineered medical device products”,“5.4 Research,development and translation of innovative biomaterials”and“5.5 Research on technical evaluation of recombinant collagens,cartilagerepair materials and antimicrobial orthopedic/dental materials”)of Chinese Drug Regulatory Science Action Plan of National Medical Products Administration。
文摘The fast development of both biomaterials and regulatory science calls for a convergence,which is addressed in this article via their link through medical products of biomaterials and related safety and efficacy evaluation.The updated definition of biomaterials,and concepts of biomaterials-related medical products and so-called medical-grade and implantable materials are firstly introduced.Then a brief overview of the concept and history of regulatory science and its assessment of safety and efficacy of medical products,as well as the currently ongoing biomaterials-related regulatory science programs are presented.Finally,the opportunities provided by regulatory science for biomaterials as well as challenges on how to develop a biomaterials-based regulatory science system are discussed.As the first article in the field to elucidate the relationship between biomaterials and regulatory science,key take-home messages include(1)biomaterials alone are not medical products;(2)regulatory authorities approve/clear final medical products,not biomaterials;(3)there is no definition/regulation on the so-called medical-grade or implantable materials;and(4)safety and efficacy refer to final medical products,not biomaterials alone.
文摘Introduction and research overview Recently,increasing need for organ transplantation and lack of donated organs have led to the rapid development of new technologies for artificial organ biofabrication.In the era of burgeoning breakthroughs around 3D bioprinting technologies,the personalization of organs and medicine is an ongoing nice vision[1–5].As one of the leading laboratories in the interdisciplinary field of materials,manufacturing and bioengineering,the Biofabrication(3D Bioprinting)Research Laboratory at Sichuan University has been engaging in the research on customized regenerativemedicine since 2012.
基金supported by National Key Research and Development Program of China(Grant Nos.2023YFC2411300,2023YFB4605800)National Natural Science Foundation of China(Grant No.32471474)+2 种基金Sichuan Science and Technology Program(Grant Nos.2024YFHZ0125,2022NSFSC1405)China Postdoctoral Science Foundation(Grant No.2022M722268)Research and Develop Program,West China Hospital of Stomatology Sichuan University(Grant No.RD-03-202406).
文摘Biofabrication,also known as bioprinting,has been widely used in the field of biomedicine.The three most important factors in biofabrication are 3D bioprinter,biomaterials to be printed(bioinks),and the printing object(application).This review provides a detailed introduction to the latest research progress in these aspects.In particularly,the bioinks for bioprinting require strict biocompatible requirements.Four typical materials,i.e.metal/alloys,ceramics,polymers,and their composites,were introduced in detail,and their printing process and application scenarios were summarized,respectively.There are many applications of biofabrication in clinical practice.The application of biofabrication in skeletal system,skin and soft tissue,cardiovascular system,digestive system,respiratory system,urinary system,nervous system,plastic surgery and medical aesthetics were briefly introduced.The applications of biofabrication has a wide range of clinical need.Biofabrication is an innovative technology that is expected to further promote the clinical precision treatments.
基金supported by the National Key Research and Development Project of China(2023YFB4605800)the Natural Science Foundation of China(32071353 and 82272561)+1 种基金the Natural Science Foundation of Sichuan Province(2024NSFSC0671,China)the 111 Project of China(B16033).
文摘Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis(OA),but directly modulating mitochondria in vivo remains a significant challenge.This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients,highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA.Consequently,we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool(FoxO3)and integrated it within a nanoengineered‘truck’(NETT,FoxO3--NETT).This was further encapsulated in injectable hydrogel microspheres(FoxO3-NETT@SMs)to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes.Collectively,these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway.As a result,FoxO3-NETT@SMs stimulate chondrocytes proliferation,migration,and ECM production in vitro,and effectively alleviate OA progression in vivo,demonstrating significant potential for clinical applications.
基金supported by the National key research and development programs of China:2022YFC2405800Beijing Natural Science Foundation:L234022supported by China NMPA Research on performance and safety evaluation of innovative biomaterial medical devices:RS2024X004.
文摘Bioactive ceramics have been used in bone tissue repair and regeneration.However,because of the complex in vivo osteogenesis process,long cycle,and difficulty of accurately tracking,the mechanism of interaction between materials and cells has yet to be fully understood,hindering its development.The ceramic microbridge micro-fluidic chip system may solve the problem and provide an in vitro method to simulate the microenvironment in vivo.Nevertheless,the complex microenvironment parameters of the chip system need to be studied in detail.Computer simulation bionics can provide clues for the setting of microenvironment parameters.This study used a computational bionic model to simulate the bone growth process in the presence of immune-related factors.The osteoblast differentiation of mesenchymal stem cells of calcium phosphate ceramics in a macrophage-dominated immune microenvironment was studied using a microfluidic chip system.The computational biomimetic model and microfluidic chip findings were basically consistent with the reported results of the animal experiments.These findings suggest that studying the osteogenic behavior of calcium phosphate ceramics using a microfluidic chip model is feasible.The method model provided in this study can be extended to other biomaterials,providing a viable path for their research and evaluation.
基金supported by the National Key Research Program of China(2023YFB4605800)the Natural Science Foundation of China(32071353)the 111 Project(B16033).
文摘The interior environment of articular cartilage in osteoarthritis(OA)presents substantial hurdles,leading to the malfunctionof chondrocytes and the breakdown of collagen II-enriched hyaline cartilage matrix.Despite this,mostclinical treatments primarily provide temporary relief from OA discomfort without arresting OA progression.This studyaimed to alleviate OA by developing intra-articular injectable dECM-enhanced hyaluronic(HE)microgels.The HEhydrogel was engineered and shaped into uniformly sized microgels using microfluidics and photopolymerizationtechniques.These microgels provided a spatiotemporal cascade effect,facilitating the rapid release of growth factorsand a slower release of ECM macromolecules and proteins.This process assisted in the recovery of OA chondrocytes’function,promoting cell proliferation,matrix synthesis,and cartilage-specific gene expression in vitro.It also effectivelyaided repair of the collagen II-enriched hyaline cartilage and significantly reduced the severity of OA,as demonstratedby radiological observation,gross appearance,histological/immunohistochemical staining,and analysisin an OA rat model in vivo.Collectively,the HE injectable microgels with spatiotemporal release of cartilage-specificmolecules have shown promise as a potential candidate for a cell-free OA therapy approach.
基金supported by National Key R&D Program of China(Grant No.2022YFC2401800)National Natural Science Foundation of China(Grant No.32301116)Sichuan Science and Technology Program(Grant No.2023 NSFSC0996).
文摘Collagen, recognized as the primary structural component of human skin, is essential for preserving dermal integrity and function. Its progressive depletion has been closely associated with structural deterioration of the dermis and the visible signs of skin aging. Among current therapeutic strategies, the injection of exogenous collagen has been established as an effective method for alleviating aging-related skin changes. In the present study, a comprehensive evaluation was conducted to assess the injectability, cellular interactions, and photoaging repair efficacy of recombinant human collagen type III(RHC). The RHC solution was found to demonstrate favorable injectability and support the adhesion and chemotactic behavior of L929 cells, while also upregulating the expression of type I and type III collagen. In co-culture systems with lipopolysaccharide-stimulated macrophages, RHC treatment suppressed macrophage proliferation and reduced the production of proinflammatory cytokines, suggesting notable immunomodulatory properties. Upon intradermal injection of RHC into photoaged rat skin, an increased density of dermal collagen fibers was observed, accompanied by a more organized and uniform fiber arrangement. Additionally, hydroxyproline content and the expressions of collagen I and III were markedly elevated in the RHC group compared with the control and hyaluronic acid groups. Collectively, these findings suggest that RHC holds considerable promise as a therapeutic agent for both medical and cosmetic purposes targeting the restoration and maintenance of youthful skin characteristics.
基金This work was supported by National Key Research and Development Program of China(2018YFC1106800)Sichuan province key research and development project(20ZDYF0191).
文摘Repair and reconstruction of large bone defect were often difficult,and bone substitute materials,including autogenous bone,allogenic bone and artificial bone,were common treatment strategies.The key to elucidate the clinical effect of these bone repair materials was to study their osteogenic capacity and immunotoxicological compatibility.In this paper,the mechanical properties,micro-CT imaging analysis,digital image analysis and histological slice analysis of the three bone grafts were investigated and compared after different time points of implantation in rat femur defect model.Autogenous bone and biphasic calcium phosphate particular artificial bone containing 61.4% HA and 38.6%β-tricalcium phosphate with 61.64%porosity and 0.8617±0.0068 g/cm^(3) den-sity(d≤2 mm)had similar and strong bone repair ability,but autogenous bone implant materials caused greater secondary damage to experimental animals;allogenic bone exhibited poor bone defect repair ability.At the early stage of implantation,the immunological indexes such as Immunoglobulin G,Immunoglobulin M concentration and CD4 cells'population of allogenic bone significantly increased in compared with those of autologous bone and artificial bone.Although the repair process of artificial bone was relatively inefficient than autologous bone graft,the low immunotoxicological indexes and acceptable therapeutic effects endowed it as an excellent alter-native material to solve the problems with insufficient source and secondary trauma of autogenous bone.
基金This study was financially supported by the National Natural Science Foundation of China(31370973,31400819)the National Key Research and Development Program of China(2016YFC1102000,2016YFC1102003)the“111”Project of China(B16033).
文摘Osteoinductivity of porous calcium phosphate(CaP)ceramics has been widely investigated and confirmed,and it might be attributed to the rapid formation of the vascular networks after in vivo implantation of the ceramics.In this study,to explore the vascularization mechanism within the CaP ceramics,the migration and differentiation of bone marrow-derived mesenchymal stem cells(BMSCs)under the stimulation of porous biphasic calcium phosphate(BCP)ceramic with excellent osteoinductivity were systematically investigated.The results indicated that the directional migration of BMSCs toward BCP ceramic occurred when evaluated by using a transwell model,and the BMSCs migration was enhanced by the seeded macrophages on the ceramic in advance.Besides,by directly culturing BMSCs on BCP ceramic discs under both in vitro and in vivo physiological environment,it was found that the differentiation of BMSCs toward vascular endothelial cells(VECs)happened under the stimulation of BCP ceramic,as was confirmed by the up-regulated gene expressions and protein secretions of VECs-related characteristic factors,including kinase insert domain receptor,von willebrand factor,vascular cell adhesion molecule-1 and cadherin 5 in the BMSCs.This study offered a possibility for explaining the origin of VECs during the rapid vascularization process after in vivo implantation of porous CaP ceramics and could give some useful guidance to reveal the vascularization mechanism of the ceramics.
基金sponsored by National Key R&D Program of China(Grant No.2018YFC1105900)National Natural Science Foundation of China(32071352)+1 种基金Sichuan Province Key R&D Program(2019YFS0007)Sichuan university Innovation Spark Project(2018SCUH0089).
文摘Supramolecular nanofiber peptide assemblies had been used to construct functional hydrogel biomaterials and achieved great progress.Here,a new class of biphenyl-tripeptides with different C-terminal amino acids sequences transposition were developed,which could self-assemble to form robust supramolecular nanofiber hydrogels from 0.7 to 13.8 kPa at ultra-low weight percent(about 0.27 wt%).Using molecular dynamics simulations to interrogate the physicochemical properties of designed biphenyl-tripeptide sequences in atomic detail,reasonable hydrogen bond interactions and“FF”brick(phenylalanine-phenylalanine)promoted the formation of supramolecular fibrous hydrogels.The biomechanical properties and intermolecular interactions were also analyzed by rheology and spectroscopy analysis to optimize amino acid sequence.Enhanced L929 cells adhesion and proliferation demonstrated good biocompatibility of the hydrogels.The storage modulus of BPAA-AFF with 10 nm nanofibers self-assembling was around 13.8 kPa,and the morphology was similar to natural extracellular matrix.These supramolecular nanofiber hydrogels could effectively support chondrocytes spreading and proliferation,and specifically enhance chondrogenic related genes expression and chondrogenic matrix secretion.Such biomimetic supramolecular short peptide biomaterials hold great potential in regenerative medicine as promising innovative matrices because of their simple and regular molecular structure and excellent biological performance.
基金This work was sponsored by the National Key Research and Development Program of China(2019YFA0110600)Science and Technology Support Program of Sichuan Province(2019YJ0161)Guangxi Key Research and Development Plan(GuikeAB16450003).
文摘Collagen is a promising material for tissue engineering,but the poor mechanical properties of collagen hydrogels,which tend to cause contraction under the action of cellular activity,make its application challengeable.In this study,the amino group of type I collagen(Col I)was modified with methacrylic anhydride(MA)and the photo-crosslinkable methacrylate anhydride modified type I collagen(CM)with three different degrees of substitution(DS)was prepared.The physical properties of CM and Col I hydrogels were tested,including micromorphology,mechanical properties and degradation properties.The results showed that the storage modulus and degradation rate of hydrogels could be adjusted by changing the DS of CM.In vitro,chondrocytes were seeded into these four groups of hydrogels and subjected to fluorescein diacetate/propidium iodide(FDA/PI)staining,cell counting kit-8(CCK-8)test,histological staining and cartilage-related gene expression analysis.In vivo,these hydrogels encapsulating chondrocytes were implanted subcutaneously into nude mice,then histological staining and sulfated glycosaminoglycan(sGAG)/DNA assays were performed.The results demonstrated that contraction of hydrogels affected behaviors of chondrocytes,and CM hydrogels with suitable DS could resist contraction of hydrogels and promote the secretion of cartilage-specific matrix in vitro and in vivo.
基金National Key R&D Project of China(Grant No.2018YFC1105900)National Natural Science Foundation of China(32071352 and 81860392)Sichuan University Innovation Spark Project(2018SCUH0089).
文摘In tissue engineering,bioactive materials play an important role,providing structural support,cell regulation and establishing a suitable microenvironment to promote tissue regeneration.As the main component of extracellular matrix,collagen is an important natural bioactive material and it has been widely used in scientific research and clinical applications.Collagen is available from a wide range of animal origin,it can be produced by synthesis or through recombinant protein production systems.The use of pure collagen has inherent disadvantages in terms of physico-chemical properties.For this reason,a processed collagen in different ways can better match the specific requirements as biomaterial for tissue repair.Here,collagen may be used in bone/cartilage regeneration,skin regeneration,cardiovascular repair and other fields,by following different processing methods,including cross-linked collagen,complex,structured collagen,mineralized collagen,carrier and other forms,promoting the development of tissue engineering.This review summarizes a wide range of applications of collagen-based biomaterials and their recent progress in several tissue regeneration fields.Furthermore,the application prospect of bioactive materials based on collagen was outlooked,aiming at inspiring more new progress and advancements in tissue engineering research.
基金supported by the National Key Research Programme of China(No.2018YFC1105900)the Sichuan Science and Technology Programme(No.2018RZ0039)the 111 Project(No.B16033).
文摘Extracellular matrix(ECM)-based biomaterials are promising candidates in cartilage tissue engineering by simulating the native microenvironment to regulate the chondrogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)without exogenous growth factors.The biological properties of ECM scaffolds are primarily depended on the original source,which would directly influence the chondrogenic effects of the ECM materials.Despite the expanding investigations on ECM scaffolds in recent years,the selection of optimized ECM materials in cartilage regeneration was less reported.In this study,we harvested and compared the articular cartilage ECM from newborn,juvenile and adult rabbits.The results demonstrated the significant differences in the mechanical strength,sulphated glycosaminoglycan and collagen contents of the different aged ECM,before and after decellularization.Consequently,different compositional and mechanical properties were shown in the three ECM-based collagen hydrogels,which exerted age-dependent chondrogenic inducibility.In general,both in vitro and in vivo results suggested that the newborn ECM promoted the most chondrogenesis of BMSCs but led to severe matrix calcification.In contrast,BMSCs synthesized the lowest amount of cartilaginous matrix with minimal calcification with adult ECM.The juvenile ECM achieved the best overall results in promoting chondrogenesis of BMSCs and preventing matrix calcification.Together,this study provides important information to our current knowledge in the design of future ECM-based biomaterials towards a successful repair of articular cartilage.
