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
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
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
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
Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) tha...Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) that sequentially drives macrophage phenotypic polarization (M0 to M1, then to M2) was constructed by integrating anti-inflammatory components and proinflammatory solvents. In vitro experiments demonstrated that the proinflammatory solvent ethanol stabilized the hydrogel structure, maintained the phenolic hydroxyl group activity, and achieved macrophages' proinflammatory transition (M0 to M1) to enhance antibacterial effects. With ethanol depletion, the hydrogel's cations and phenolic hydroxyl groups synergistically regulated macrophages' anti-inflammatory transition (M1 to M2) to initiate regeneration. In the anti-contraction full-thickness wound model with infection, this hydrogel effectively eliminated bacteria and even achieved anti-inflammatory M2 macrophage accumulation at three days post-surgery, accelerated angiogenesis and collagen deposition. By sequentially driving macrophage phenotypic polarization, this injectable immunoregulatory hydrogel will bring new guidance for the care and treatment of infected wounds.展开更多
Locoregional recurrence and distant metastasis of breast cancer still pose a significant risk for patients’survival.To address the clinical challenge,functional absorbable sponges(HA-SH/PP-Dox/Lap/COL I(HCNPs))were c...Locoregional recurrence and distant metastasis of breast cancer still pose a significant risk for patients’survival.To address the clinical challenge,functional absorbable sponges(HA-SH/PP-Dox/Lap/COL I(HCNPs))were constructed by biomimetic extracellular matrix of collagen I/hyaluronic acid complex conjugated with doxorubicin/lapatinib(Dox/Lap)-loaded nanoparticles.The HCNPs sponge exhibited excellent clotting ability and blood absorption rate.Worthily,Dox/Lap-loaded nanoparticles were synchronously endowed with a large number of oligo hyaluronic acid segments after degradation,which thus enhanced the ability of targeting into CD44-overexpressed tumor cells.The implantable HCNPs sponge in resected cavity of postoperative 4T1 models inhibited the spread of scattered tumor cells by absorbing the inevitable bleeding.More importantly,CD44 targeted nanoparticle with suitable Dox/Lap proportion continuously released from sponge to kill tumor cells of surrounding HCNPs and those remaining at surgical margin,thus prevented local recurrence as well as distant metastasis.Therefore,the functional HCNPs sponge might provide a safer and more effective strategy for postoperative treatment of cancer.展开更多
The regeneration of articular cartilage posed a formidable challenge due to the restricted treatment efficacy of exist-ing therapies.Scaffold-based tissue engineering emerges as a promising avenue for cartilage recons...The regeneration of articular cartilage posed a formidable challenge due to the restricted treatment efficacy of exist-ing therapies.Scaffold-based tissue engineering emerges as a promising avenue for cartilage reconstitution.However,most scaffolds exhibit inadequate mechanical characteristics,poor biocompatibility,or absent cell adhesion sites.In this study,cartilage-like protein-polysaccharide hybrid hydrogel based on DOPA-modified hyaluronic acid,bovine type Ⅰ collagen(Col Ⅰ),and recombinant humanized type Ⅱ collagen(rhCol Ⅱ),denoted as HDCR.HDCR hydrogels possessed the advantage of injectability and in situ crosslinking through pH adjustment.Moreover,HDCR hydrogels exhibited a manipulable degradation rate and favorable biocompatibility.Notably,HDCR hydrogels significantly induced chondrogenic differentiation of rabbit bone marrow mesenchymal stem cells in vitro,as demonstrated by the upregulation of crucial chondrogenic genes(type Ⅱ collagen,aggrecan)and the abundant accumulation of glycosaminoglycan.This approach presented a strategy to manufacture injectable,biodegradable scaffolds based on cartilage-like protein-polysaccharide polymers,offering a minimally invasive solution for cartilage repair.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
The objective of regenerative wound healing dressings is to accelerate skin tissue regeneration and restore normal physiological function at wound sites.Achieving this goal requires biomaterials capable of repairing d...The objective of regenerative wound healing dressings is to accelerate skin tissue regeneration and restore normal physiological function at wound sites.Achieving this goal requires biomaterials capable of repairing distinct phases of wound healing in a way that balanc es material function,degradation,safety,and tissue growth.In this study,we introduced a novel dual-stage wound dressing system comprising methacrylic anhydride-modified recombinant humanized type Ⅲ collagen(rhCol Ⅲ-MA) and methacrylic anhydride-modified dopamine(DMA)(RMDM),which was synthesized through free radical polymerization and π-π stacking.Within this system,RMDM was formulated into two forms with identic al compositions:hydrogel and sponge,tailored for application across various stages of wound repair.These materials displayed favorable hemocompatibility,biocompatibility,antioxidant properties,and angiogenic potential in vitro.Moreover,the in vivo experiments also demonstrated that sponges could rapidly stop the bleeding of wounds in mouse tail amputation and liver incision models.Notably,the sponge/gel(S/G) system accelerated wound healing compared to individual sponge and gel treatments in a rat full-thickness skin wound model,underscoring the synergistic benefits of combining sponge and gel materials for wound repair at different stages.Therefo re,this research provides valuable insights into designing advanced biomaterials that can be tailored to specific stages of wound healing,which may have significant potential for biomedical applications.展开更多
基金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.
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.
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 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National Key R&D Project of China(No.2022YFC2401800)National Natural Science Foundation of China(32071352 and 32271419).
文摘Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) that sequentially drives macrophage phenotypic polarization (M0 to M1, then to M2) was constructed by integrating anti-inflammatory components and proinflammatory solvents. In vitro experiments demonstrated that the proinflammatory solvent ethanol stabilized the hydrogel structure, maintained the phenolic hydroxyl group activity, and achieved macrophages' proinflammatory transition (M0 to M1) to enhance antibacterial effects. With ethanol depletion, the hydrogel's cations and phenolic hydroxyl groups synergistically regulated macrophages' anti-inflammatory transition (M1 to M2) to initiate regeneration. In the anti-contraction full-thickness wound model with infection, this hydrogel effectively eliminated bacteria and even achieved anti-inflammatory M2 macrophage accumulation at three days post-surgery, accelerated angiogenesis and collagen deposition. By sequentially driving macrophage phenotypic polarization, this injectable immunoregulatory hydrogel will bring new guidance for the care and treatment of infected wounds.
基金sponsored by the National Natural Science Foundation of China(Nos.51973136 and 32071352)the Open Project Program of the Third Affiliated Hospital of Xinxiang Medical University(No.KFKTZD202102).
文摘Locoregional recurrence and distant metastasis of breast cancer still pose a significant risk for patients’survival.To address the clinical challenge,functional absorbable sponges(HA-SH/PP-Dox/Lap/COL I(HCNPs))were constructed by biomimetic extracellular matrix of collagen I/hyaluronic acid complex conjugated with doxorubicin/lapatinib(Dox/Lap)-loaded nanoparticles.The HCNPs sponge exhibited excellent clotting ability and blood absorption rate.Worthily,Dox/Lap-loaded nanoparticles were synchronously endowed with a large number of oligo hyaluronic acid segments after degradation,which thus enhanced the ability of targeting into CD44-overexpressed tumor cells.The implantable HCNPs sponge in resected cavity of postoperative 4T1 models inhibited the spread of scattered tumor cells by absorbing the inevitable bleeding.More importantly,CD44 targeted nanoparticle with suitable Dox/Lap proportion continuously released from sponge to kill tumor cells of surrounding HCNPs and those remaining at surgical margin,thus prevented local recurrence as well as distant metastasis.Therefore,the functional HCNPs sponge might provide a safer and more effective strategy for postoperative treatment of cancer.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFC2401800)Fundamental Research Funds for the Central Universities(2022SCU12104)+1 种基金the National Natural Science Foundation of China(Grant No.51973136)Sichuan University postdoctoral interdisciplinary Innovation Fund.
文摘The regeneration of articular cartilage posed a formidable challenge due to the restricted treatment efficacy of exist-ing therapies.Scaffold-based tissue engineering emerges as a promising avenue for cartilage reconstitution.However,most scaffolds exhibit inadequate mechanical characteristics,poor biocompatibility,or absent cell adhesion sites.In this study,cartilage-like protein-polysaccharide hybrid hydrogel based on DOPA-modified hyaluronic acid,bovine type Ⅰ collagen(Col Ⅰ),and recombinant humanized type Ⅱ collagen(rhCol Ⅱ),denoted as HDCR.HDCR hydrogels possessed the advantage of injectability and in situ crosslinking through pH adjustment.Moreover,HDCR hydrogels exhibited a manipulable degradation rate and favorable biocompatibility.Notably,HDCR hydrogels significantly induced chondrogenic differentiation of rabbit bone marrow mesenchymal stem cells in vitro,as demonstrated by the upregulation of crucial chondrogenic genes(type Ⅱ collagen,aggrecan)and the abundant accumulation of glycosaminoglycan.This approach presented a strategy to manufacture injectable,biodegradable scaffolds based on cartilage-like protein-polysaccharide polymers,offering a minimally invasive solution for cartilage repair.
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supported by National Key R&D Program of China(Grant No.2022YFC2401800)National Natural Science Foundation of China(Grant No.32301116)Sichuan Science and Technology Program(Grant No.2023NSFSC0996)
文摘The objective of regenerative wound healing dressings is to accelerate skin tissue regeneration and restore normal physiological function at wound sites.Achieving this goal requires biomaterials capable of repairing distinct phases of wound healing in a way that balanc es material function,degradation,safety,and tissue growth.In this study,we introduced a novel dual-stage wound dressing system comprising methacrylic anhydride-modified recombinant humanized type Ⅲ collagen(rhCol Ⅲ-MA) and methacrylic anhydride-modified dopamine(DMA)(RMDM),which was synthesized through free radical polymerization and π-π stacking.Within this system,RMDM was formulated into two forms with identic al compositions:hydrogel and sponge,tailored for application across various stages of wound repair.These materials displayed favorable hemocompatibility,biocompatibility,antioxidant properties,and angiogenic potential in vitro.Moreover,the in vivo experiments also demonstrated that sponges could rapidly stop the bleeding of wounds in mouse tail amputation and liver incision models.Notably,the sponge/gel(S/G) system accelerated wound healing compared to individual sponge and gel treatments in a rat full-thickness skin wound model,underscoring the synergistic benefits of combining sponge and gel materials for wound repair at different stages.Therefo re,this research provides valuable insights into designing advanced biomaterials that can be tailored to specific stages of wound healing,which may have significant potential for biomedical applications.
