Four types of Mg-5Zn porous scaffolds with different pore geometries,including body-centered cubic(bcc),the rhombic dodecahedron(RD),gyroid(G),and primitive(P)types,were designed and fabricated using selective laser m...Four types of Mg-5Zn porous scaffolds with different pore geometries,including body-centered cubic(bcc),the rhombic dodecahedron(RD),gyroid(G),and primitive(P)types,were designed and fabricated using selective laser melting.Their forming quality,compression mechanical properties,and degradation behavior were investigated.Results indicate that the fabricated scaffolds exhibit good dimensional accuracy,and the surface chemical polishing treatment significantly improves the forming quality and reduces porosity error in porous scaffolds.Compared to the ones with rod structures(bcc,RD),the scaffolds with surface structures(G,P)have less powder particle adhesion.The G porous scaffold exhibits the best forming quality for the same design porosity.The predominant failure mode of scaffolds during compression is a 45°shear fracture.At a porosity of 75%,the compression property of all scaffolds meets the compressive property requirements of cancellous bone,while bcc and G structures show relatively better compression property.After immersion in Hank's solution for 168 h,the B-2-75% pore structure scaffold exhibits severe localized corrosion,with fractures in partial pillar connections.In contrast,the G-3-75% pore structure scaffold mainly undergoes uniform corrosion,maintaining structural integrity,and its corrosion rate and loss of compressive properties are less than those of the B-2-75%structure.After comparison,the G-pore structure scaffold is preferred.展开更多
Exosomes derived from bone mesenchymal stem cells(BMSCs)show promising potential for treating bone defects.However,their clinical application is hindered by low yield and insufficient repair ability.Three-dimensional(...Exosomes derived from bone mesenchymal stem cells(BMSCs)show promising potential for treating bone defects.However,their clinical application is hindered by low yield and insufficient repair ability.Three-dimensional(3D)mechanical stimulation has been a well-known method for enhancing exosome secretion;however,the traditional stimulation process is always achieved by controlling the displacement of manipulators,which may induce uneven loading distribution and degradation of stimulation strength.Here,we propose a micro-stretching manipulator that automatically controls the stretching force applied to gelatin methacryloyl(GelMA)/hyaluronic acid methacryloyl(HAMA)hybrid hydrogel sheets containing BMSCs within an incubator.To ensure the structural stability of the sheets after long-term stretching,the mixing ratio between GelMA and HAMA was optimized according to the mechanical property response of the sheets to cyclical loading.Subsequently,force-controlled mechanical loading was applied to the BMSC-laden sheets to produce exosomes.Compared with displacement control,force-controlled loading provides a more stable force stimulation,thereby enhancing exosome secretion.Furthermore,continuously stimulated exosomes exhibited a stronger capacity for promoting osteogenic differentiation of BMSCs and facilitating the repair of bone defects in a rat model.These findings suggest that force-controlled loading of cell-laden hydrogels offers a novel approach for the production of BMSC-derived exosomes and their application in bone repair.展开更多
Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize ...Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize the bone regeneration.However,how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood.Here,by employing single-cell transcriptional profiling combined with lineage-specific tracing models,we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly,our data demonstrated that the Sonic hedgehog(Shh)signaling was responsible for the transition process initiation,which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers.Collectively,these findings depict an injuryspecific niche signal-mediated Plp1-lineage cells transition towards Gli1+MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.展开更多
With attractive research and development of biomaterials, more and more opportunities have been brought to the treatments of human tissue repairs. The implant is usually no need to exist in the body accompanied with t...With attractive research and development of biomaterials, more and more opportunities have been brought to the treatments of human tissue repairs. The implant is usually no need to exist in the body accompanied with the recovery or regeneration of the tissue lesions, and the long-term effect of exotic substance to human body should be reduced as lower as possible. For this purpose, biodegradable materials, including polymers, magnesium alloys and ceramics, have attracted much attention for medical applications due to their biodegradable characters in body environment. This paper in turn introduces these three different types of widely studied biodegradable materials as well as their advantages as implants in applications for bone repairs. Relevant history and research progresses are summarized.展开更多
Bone is a highly vascularized tissue, although this aspect of bone is often overlooked. In this article, the importance of blood flow in bone repair and regeneration will be reviewed. First, the skeletal vascular anat...Bone is a highly vascularized tissue, although this aspect of bone is often overlooked. In this article, the importance of blood flow in bone repair and regeneration will be reviewed. First, the skeletal vascular anato- my, with an emphasis on long bones, the distinct mechanisms for vascularizing bone tissue, and methods for remodeling existing vasculature are discussed. Next, techniques for quantifying bone blood flow are briefly summarized. Finally, the body of experimental work that demonstrates the role of bone blood flow in fracture healing, distraction osteogenesis, osteoporosis, disuse osteopenia, and bone grafting is examined. These results illustrate that adequate bone blood flow is an important clinical consideration, particularly during bone regeneration and in at-risk patient groups.展开更多
Bone defects caused by trauma,tumor,or osteoarthritis remain challenging due to the lack of effective treatments in clinic.Stem cell transplantation has emerged as an alternative approach for bone repair and attracted...Bone defects caused by trauma,tumor,or osteoarthritis remain challenging due to the lack of effective treatments in clinic.Stem cell transplantation has emerged as an alternative approach for bone repair and attracted widespread attention owing to its excellent biological activities and therapy effect.The attempts to develop this therapeutic approach focus on the generation of effective cell delivery vehicles,since the shortcomings of direct injection of stem cells into target tissues.Here,we developed a novel core-shell microcapsule with a stem cell-laden core and a biomass shell by using all-aqueous phase microfluidic electrospray technology.The designed core-shell microcapsules showed a high cell viability during the culture procedure.In addition,the animal experiments exhibited that stem cell-laden core-shell microcapsules have good biocompatibility and therapeutic effect for bone defects.This study indicated that the core-shell biomass microcapsules generated by microfluidic electrospray have promising potential in tissue engineering and regenerative medicine.展开更多
Biomedical applications of nanomaterials are exponentially increasing every year due to analogy to various cell receptors, ligands, structural proteins, and genetic materials(that is, DNA). In bone tissue, nanoscale m...Biomedical applications of nanomaterials are exponentially increasing every year due to analogy to various cell receptors, ligands, structural proteins, and genetic materials(that is, DNA). In bone tissue, nanoscale materials can provide scaffold for excellent tissue repair via mechanical stimulation, releasing of various loaded drugs and mediators, 3D scaffold for cell growth and differentiation of bone marrow stem cells to osteocytes. This review will therefore highlight recent advancements on tissue and nanoscale materials interaction.展开更多
In this study, we developed a simple approach for the controllable growth of whitlockite （WH） on a β- tricalcium phosphate surface and investigated its cell viability via CCK-8, its live-dead staining and its alkal...In this study, we developed a simple approach for the controllable growth of whitlockite （WH） on a β- tricalcium phosphate surface and investigated its cell viability via CCK-8, its live-dead staining and its alkaline phosphatase activity. Herein, WH with controllable morphologies was prepared by regulating the hydrothermal reaction conditions. The results of scanning electron microscopy, X-ray diffraction and X- ray photoelectron spectroscopy indicated that pure hexagonal plates of WH were prepared successfully. In vitro cell experiments showed that WH possessed excellent biocompatibility and effectively promoted the adhesion and proliferation of mouse bone mesenchymal stem cells. The osteogenesis of the WH was also enhanced. The obtained WH was expected to be utilized for promising applications as implantable block materials for bone repair.展开更多
We investigate high-modulus degradable materials intended to replace metals in biomedical applications.These are typically composites comprising a polylactide(PLA)matrix reinforced with phosphate glass fibres,which pr...We investigate high-modulus degradable materials intended to replace metals in biomedical applications.These are typically composites comprising a polylactide(PLA)matrix reinforced with phosphate glass fibres,which provide reinforcement similar to E-glass but are entirely degradable in water to produce,principally,calcium phosphate.We have made composites using a variety of fibre architectures,from non-woven random mats to unidirectional fibre tapes.Flexural properties in the region of 30 GPa modulus and 350 MPa strength have been achieved-directly comparable to quoted values for human cortical bone.In collaboration with other groups we have begun to consider the development of foamed systems with structures mimicking cancellous bone and this has shown significant promise.The fibres in these foamed structures provide improved creep resistance and reinforcement of the pore walls.To date the materials have exhibited excellent cellular responses in vitro and further studies are due to include consideration of the surface character of the materials and the influence of this on cell interaction, both with the composites and the glass fibres themselves,which show promise as a standalone porous scaffold.展开更多
Doxycycline （DOX） exhibits anti-inflammatory and MMP inhibitory properties. The objectives of this study were to evaluate the effects of DOX on alveolar bone repair. Controls （CTL） and DOX-treated （10 and 25 mg. ...Doxycycline （DOX） exhibits anti-inflammatory and MMP inhibitory properties. The objectives of this study were to evaluate the effects of DOX on alveolar bone repair. Controls （CTL） and DOX-treated （10 and 25 mg. kg- 1） molars were extracted, and rats were killed 7 or 14 days later. The maxillae were processed and subjected to histological and immunohistochemical assays. Hematoxylin-eosin staining （7th day） revealed inflammation in the CTL group that was partly reversed after DOX treatment. On the 14th day, the CTL group exhibited bone neoformation, conjunctive tissue, re-epithelization and the absence of inflammatory infiltrate. DOX-treated groups exhibited complete re-epithelization, tissue remodelling and almost no inflammation. Picrosirius red staining in the DOXlO group （7th and 14th days） revealed an increased percentage of type I and III collagen fibres compared with the CTL and DOX25 groups. The DOXlO and DOX25 groups exhibited increases in osteoblasts on the 7th and 14th days. However, there were fewer osteoclasts in the DOXlO and DOX25 groups on the 7th and 14th days. Wnt-lOb- immunopositive cells increased by 130% and 150% on the 7th and 14th days, respectively, in DOX-treated groups compared with the CTL group. On the 7th day, Dickkopf （Dkk）-I immunostaining was decreased by 63% and 46% in the DOXlO and DOX25 groups, respectively. On the 14th day, 69% and 42% decreases in immunopositive cells were observed in the DOXlO and DOX25 groups, respectively, compared with the CTL group. By increasing osteoblasts, decreasing osteoclasts, activating Wnt lOb and neutralising Dkk, DOX is a potential candidate for bone repair in periodontal diseases.展开更多
A new kind of nano-biomaterials of nano apatite （ NA ） and polyamide8063 （ PA ） composite was prepared by direct using NA slurry. The experimental results showed that the NA content in the composite was similar to...A new kind of nano-biomaterials of nano apatite （ NA ） and polyamide8063 （ PA ） composite was prepared by direct using NA slurry. The experimental results showed that the NA content in the composite was similar to that of natural bone. Interfrace chemical bonding was formed between NA and PA. The NA keeps the original morphological structure with a crystal size of 10- 30 nm in width by 50- 90 nm in length with a ratio of - 2.5 and distributed uniformly in thepolymer. The synthetic nano-biomaterials could be one of the best bioactive materials for load-bearing bone repair or substitution materials.展开更多
Objective:To prepare a bone repair material with certain mechanical strength and biological activity,this paper used calcium sulfate hemihydrate(CSH)powder compounded with calcium hydroxide(Ca(OH)2)powder to prepare a...Objective:To prepare a bone repair material with certain mechanical strength and biological activity,this paper used calcium sulfate hemihydrate(CSH)powder compounded with calcium hydroxide(Ca(OH)2)powder to prepare a bone repair scaffold material for physicochemical property characterization and testing.Methods:The physical and chemical properties and characterization of the dried and cured bone repair materials were determined by Fourier infrared spectroscopy(FT-IR),X-ray diffraction(XRD),and scanning electron microscopy;Universal material testing machine to determine the mechanical and mechanical strength of composite materials.Results:XRD showed that the structure of the composite material phase at 5%concentration was calcium sulfate hemihydrate and calcium hydroxide after hydration.The FT-IR and XRD analyses were consistent.Scanning electron microscopy(SEM)results showed that calcium hydroxide was uniformly dispersed in the hemihydrate calcium sulfate material.0%,1%,5%,and 10%specimen groups had compressive strengths of 3.86±3.1,5.27±1.28,8.22±0.96,and 14.4±3.28 MPa.10%addition of calcium hydroxide significantly improved the mechanical strength of the composites,but also reduced the the porosity of the material.Conclusion:With the addition of calcium hydroxide,the CSH-Ca(OH)2 composite was improved in terms of mechanical material and is expected to be a new type of bone repair material.展开更多
The extracellular matrix-associated bone morphogenetic proteins(BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively partici...The extracellular matrix-associated bone morphogenetic proteins(BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed in many preclinical and clinical studies exploring their chondrogenic or osteoinductive potential in several animal model defects and in human diseases. During years of research in particular two BMPs, BMP2 and BMP7 have gained the podium for their use in the treatment of various cartilage and bone defects. In particular they have been recently approved for employment in non-union fractures as adjunct therapies. On the other hand, thanks to their potentialities in biomedical applications, there is a growing interest in studying the biology of mesenchymal stem cell(MSC), the rules underneath their differentiation abilities, and to test their true abilities in tissue engineering. In fact, the specific differentiation of MSCs into targeted celltype lineages for transplantation is a primary goal of the regenerative medicine. This review provides an overview on the current knowledge of BMP roles and signaling in MSC biology and differentiation capacities. In particular the article focuses on the potential clinical use of BMPs and MSCs concomitantly, in cartilage and bone tissue repair.展开更多
Bone defect repair is a complex physiological process,starting with early modulation by the inflammatory im-mune system,and involves multiple physiological events,including angiogenesis,osteogenic differentiation,and ...Bone defect repair is a complex physiological process,starting with early modulation by the inflammatory im-mune system,and involves multiple physiological events,including angiogenesis,osteogenic differentiation,and mineralization.Biomaterial can regulate inflammatory responses through relevant immune cells in the local immune microenvironment of the implant-bone interface which is a hot topic in the field of regenerative medicine.Currently,Mg^(2+)regulates immune cells in the bone microenvironment to promote osteogenesis and angiogenesis mainly focuses on macrophages,but there is relatively little research on T cells.At the same time,the effective delivery and release of Mg^(2+)remains a challenge.To address these issues,we designed a new ther-mosensitive hyaluronic acid-hydroxypropyl chitin hydrogel(HPCH@HA)that has good affinity for Mg^(2+)and can sustained release it.In vitro,nano MgO loaded complex hydrogels effectively induced macrophage polarization from M0 phenotype to M2 phenotype and simultaneously activate T lymphocytes which also promoted human adipose-derived stem cells(hADSCs)osteogenic differentiation and mineralization and human umbilical vein endothelial cells(HUVECs)angiogenesis.In vivo,at the early stage of repair,the composite hydrogel has a good repair effect on mouse skull critical defect.All these results show that our designed composite hydrogels can effectively regulate the immune microenvironment of bone tissue and promoting the formation of mature bone in large bone defects and supporting in situ bone regeneration without the use of exogenous cells or inducers.It’s a promising candidate as immunomodulatory biomaterials for bone tissue engineering purposes.展开更多
Bones can fulfill functions in movement,attachment,and protection of internal organs.Bone diseases caused by ageing,trauma,infection,and other reasons may seriously affect the daily life of patients.Magnesium ions are...Bones can fulfill functions in movement,attachment,and protection of internal organs.Bone diseases caused by ageing,trauma,infection,and other reasons may seriously affect the daily life of patients.Magnesium ions are closely associated with the maintenance of bone health.Integrating magnesium ions into delivery systems and hydrogels can improve their application,thus directly acting on the osteoblast cell lineage and influencing the proliferation and differentiation of relevant cells.The slow release of magnesium ions allows for their effects on the target site for a long time,reducing the clearance of magnesium ions in the body,which significantly contributes to bone repair.Magnesium-based bioalloy scaffolds have received widespread attention for their favourable biocompatibility,degradability,and boneforming properties and play an important role in bone regeneration and repair.This article presents a review on the role and mechanism of magnesium-containing materials in bone repair and regeneration.By discussing the current challenges and future directions for magnesium-containing biomaterials,new insights are provided into the development of these materials in the field of orthopaedics.In conclusion,magnesium-containing biomaterials have great application value in orthopaedics.展开更多
Background:Bushen Zhuanggu Formula(BZF),derived from the classic Yougui Pills,has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head(NONFH),particularly by promoting ...Background:Bushen Zhuanggu Formula(BZF),derived from the classic Yougui Pills,has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head(NONFH),particularly by promoting bone repair.However,its underlying mechanisms remain unclear.Objective:This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH.Materials and methods:A total of 518 potential BZF targets were identified from the ETCMv2.0 database.Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls.A drug target-disease gene interaction network was constructed to identify candidateBZF targets involved in NONFH pathogenesis.In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH.Results:Network analysis identified key pathways associated with blood circulation obstruction,immune-inflammatory imbalance,and abnormal bone metabolism.Protein kinase C alpha(PKCA),Ras proto-oncogene(RAS),mitogen-activated protein kinase 3(ERK),ETS proto-oncogene 1(ETS1),and receptor activator of nuclear factor-kB ligand(RANKL)formed a signaling axis implicated in NONFH pathogenesis.BZF treatment alleviated joint inflammation,preserved trabecular bone morphology,reduced bone loss,and promoted bone repair.Mechanistically,BZF significantly downregulated the expression of PKCA,RAS,ERK,ETS1,and RANKL,improved blood circulation,and inhibited osteoclast activation while promoting osteoblast activation.Conclusion:BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis,thereby reversing dysregulated bone metabolism.展开更多
Endochondral bone formation is an important route for bone repair.Although emerging evidence has revealed the functions of long non-coding RNAs(lncRNAs)in bone and cartilage development,the effect of lncRNAs in endoch...Endochondral bone formation is an important route for bone repair.Although emerging evidence has revealed the functions of long non-coding RNAs(lncRNAs)in bone and cartilage development,the effect of lncRNAs in endochondral bone repair is still largely unknown.Here,we identified a lncRNA,named Hypertrophic Chondrocyte Angiogenesis-related lncRNA(HCAR),and proved it to promote the endochondral bone repair by upregulating the expression of matrix metallopeptidase 13(Mmp13)and vascular endothelial growth factorα(Vegfa)in hypertrophic chondrocytes.Lnc-HCAR knockdown in hypertrophic chondrocytes restrained the cartilage matrix remodeling and decrease the CD31hiEmcnhi vessels number in a bone repair model.Mechanistically,we proved that lnc-HCAR was mainly enriched in the cytoplasm using fluorescence in situ hybridization(FISH)assay,and it acted as a molecular sponge for miR-15b-5p.Further,in hypertrophic chondrocytes,lnc-HCAR competitively bound to miR-15b-5p to increase Vegfa and Mmp13 expression.Our results proved that lncRNA is deeply involved in endochondral bone repair,which will provide a new theoretical basis for future strategies for promoting fracture healing.展开更多
Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue en...Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue engineering scaffolds is of great significance for bone repair.This study synthesized copper(Cu)-doped mesoporous silica nanoparticles(Cu@MSN)modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN(Cu@MSNMA).Furtheremore,bio-mimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution.This hydrogel achieves multi-modal bone tissue biomimicry:(ⅰ)GelMA/gelatin mimics the matrix components in bone ECM,ensuring biocompatibility while promoting cellular behavior(such as adhesion,proliferation,and differentiation);(ⅱ)GelMA/gela-tin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure,achieving structural and mechanical biomimicry to provide necessary support for bone defects;(ⅲ)The elemental biomimicry of Si and Cu in Cu@MSNMA achieves efficient osteogenic induction.The effect of different proportions of Cu@MSNMA on the physi-cal properties of the composite hydrogels was investigated to determine the optimal proportion.The results indicated that the mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio.Notably,5%NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel.In vitro and vivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition.In conclusion,the proposed nanocomposite hydrogel with biomimetic components and ion-regulating properties can serve as a multifunctional scaffold,offering antimicrobial properties for infected bone regeneration,and guide for future research in bone regeneration and three-dimensional printing.展开更多
The process of bone repair is highly regulated by a large number of bioactive factors.Thus,a“cocktail”of bioactive factors supplemented to the defect sites is desirable for bone repair.In this regard,small extracell...The process of bone repair is highly regulated by a large number of bioactive factors.Thus,a“cocktail”of bioactive factors supplemented to the defect sites is desirable for bone repair.In this regard,small extracellular vesicles(sEVs)derived from mesenchymal stem cells hold great potential in tissue repair.Nevertheless,the poor homing and retention of sEVs greatly limited their possible clinical application.In the present work,DMPE-PEG-CREKA was inserted into the membrane of sEVs released from adipose-derived mesenchymal stem cells to obtain CREKA functionalized sEVs(CREKA-sEVs),which could target fibrin to accumulate and retain in bone defects.Our results showed that CREKA-sEVs,like sEVs,promoted the osteogenic differentiation of BMSCs,the angiogenic property of HUVECs,and modulated the polarization of macrophages in vitro.Furthermore,due to the improved fibrin-binding and retention capacity of CREKA-sEVs,they enhanced the bone repair substantially in the rat femoral defect model.This study provided a new strategy to improve the therapeutic efficiency of sEVs and showed that CREKA-sEVs had great application value in bone tissue repair.展开更多
基金Science and Technology Planning Project of Inner Mongolia Science and Technology Department(2022YFSH0021)Key Research and Development Program of Shaanxi Province(2024SF2-GJHX-14,2021SF-296)。
文摘Four types of Mg-5Zn porous scaffolds with different pore geometries,including body-centered cubic(bcc),the rhombic dodecahedron(RD),gyroid(G),and primitive(P)types,were designed and fabricated using selective laser melting.Their forming quality,compression mechanical properties,and degradation behavior were investigated.Results indicate that the fabricated scaffolds exhibit good dimensional accuracy,and the surface chemical polishing treatment significantly improves the forming quality and reduces porosity error in porous scaffolds.Compared to the ones with rod structures(bcc,RD),the scaffolds with surface structures(G,P)have less powder particle adhesion.The G porous scaffold exhibits the best forming quality for the same design porosity.The predominant failure mode of scaffolds during compression is a 45°shear fracture.At a porosity of 75%,the compression property of all scaffolds meets the compressive property requirements of cancellous bone,while bcc and G structures show relatively better compression property.After immersion in Hank's solution for 168 h,the B-2-75% pore structure scaffold exhibits severe localized corrosion,with fractures in partial pillar connections.In contrast,the G-3-75% pore structure scaffold mainly undergoes uniform corrosion,maintaining structural integrity,and its corrosion rate and loss of compressive properties are less than those of the B-2-75%structure.After comparison,the G-pore structure scaffold is preferred.
基金support from the National Key Research and Development Program of China(No.2021YFB3802105-3)the National Natural Science Foundation of China(No.62173043).
文摘Exosomes derived from bone mesenchymal stem cells(BMSCs)show promising potential for treating bone defects.However,their clinical application is hindered by low yield and insufficient repair ability.Three-dimensional(3D)mechanical stimulation has been a well-known method for enhancing exosome secretion;however,the traditional stimulation process is always achieved by controlling the displacement of manipulators,which may induce uneven loading distribution and degradation of stimulation strength.Here,we propose a micro-stretching manipulator that automatically controls the stretching force applied to gelatin methacryloyl(GelMA)/hyaluronic acid methacryloyl(HAMA)hybrid hydrogel sheets containing BMSCs within an incubator.To ensure the structural stability of the sheets after long-term stretching,the mixing ratio between GelMA and HAMA was optimized according to the mechanical property response of the sheets to cyclical loading.Subsequently,force-controlled mechanical loading was applied to the BMSC-laden sheets to produce exosomes.Compared with displacement control,force-controlled loading provides a more stable force stimulation,thereby enhancing exosome secretion.Furthermore,continuously stimulated exosomes exhibited a stronger capacity for promoting osteogenic differentiation of BMSCs and facilitating the repair of bone defects in a rat model.These findings suggest that force-controlled loading of cell-laden hydrogels offers a novel approach for the production of BMSC-derived exosomes and their application in bone repair.
基金supported by the National Natural Science Foundation of China(grants 81970910 and 82370931)Jiangsu Province Capability Improvement Project through Science,Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit(YJXYYJSDW4)Jiangsu Provincial Medical Innovation Center(CXZX202227).
文摘Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize the bone regeneration.However,how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood.Here,by employing single-cell transcriptional profiling combined with lineage-specific tracing models,we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly,our data demonstrated that the Sonic hedgehog(Shh)signaling was responsible for the transition process initiation,which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers.Collectively,these findings depict an injuryspecific niche signal-mediated Plp1-lineage cells transition towards Gli1+MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.
基金the financial support of the National Basic Research Program of China(973 Program, No.2012CB619101)
文摘With attractive research and development of biomaterials, more and more opportunities have been brought to the treatments of human tissue repairs. The implant is usually no need to exist in the body accompanied with the recovery or regeneration of the tissue lesions, and the long-term effect of exotic substance to human body should be reduced as lower as possible. For this purpose, biodegradable materials, including polymers, magnesium alloys and ceramics, have attracted much attention for medical applications due to their biodegradable characters in body environment. This paper in turn introduces these three different types of widely studied biodegradable materials as well as their advantages as implants in applications for bone repairs. Relevant history and research progresses are summarized.
基金Supported by grants from the National Institutes of Health(R01 AR050211P30 AR057235)
文摘Bone is a highly vascularized tissue, although this aspect of bone is often overlooked. In this article, the importance of blood flow in bone repair and regeneration will be reviewed. First, the skeletal vascular anato- my, with an emphasis on long bones, the distinct mechanisms for vascularizing bone tissue, and methods for remodeling existing vasculature are discussed. Next, techniques for quantifying bone blood flow are briefly summarized. Finally, the body of experimental work that demonstrates the role of bone blood flow in fracture healing, distraction osteogenesis, osteoporosis, disuse osteopenia, and bone grafting is examined. These results illustrate that adequate bone blood flow is an important clinical consideration, particularly during bone regeneration and in at-risk patient groups.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(52073060 and 61927805)the Shenzhen Fundamental Research Program(JCYJ20190813152616459).
文摘Bone defects caused by trauma,tumor,or osteoarthritis remain challenging due to the lack of effective treatments in clinic.Stem cell transplantation has emerged as an alternative approach for bone repair and attracted widespread attention owing to its excellent biological activities and therapy effect.The attempts to develop this therapeutic approach focus on the generation of effective cell delivery vehicles,since the shortcomings of direct injection of stem cells into target tissues.Here,we developed a novel core-shell microcapsule with a stem cell-laden core and a biomass shell by using all-aqueous phase microfluidic electrospray technology.The designed core-shell microcapsules showed a high cell viability during the culture procedure.In addition,the animal experiments exhibited that stem cell-laden core-shell microcapsules have good biocompatibility and therapeutic effect for bone defects.This study indicated that the core-shell biomass microcapsules generated by microfluidic electrospray have promising potential in tissue engineering and regenerative medicine.
基金funded by the 863 project(2015AA020502)National Natural Science Foundation of China(61401217,61527806)+1 种基金Natural Science Foundation of Jiangsu Province(BK20140900)the Economical Forest Cultivation and Utilization of 2011 Collaborative Innovation Center in Hunan Province[(2013)448]
文摘Biomedical applications of nanomaterials are exponentially increasing every year due to analogy to various cell receptors, ligands, structural proteins, and genetic materials(that is, DNA). In bone tissue, nanoscale materials can provide scaffold for excellent tissue repair via mechanical stimulation, releasing of various loaded drugs and mediators, 3D scaffold for cell growth and differentiation of bone marrow stem cells to osteocytes. This review will therefore highlight recent advancements on tissue and nanoscale materials interaction.
基金financially supported by the National Basic Research Programme of China(Grant No.2012CB619100)the National Natural Science Foundation of China(Grant Nos.51232002and 51603074)+2 种基金the Science and Technology Programme of Guangzhou city(Grant No.201607010234)the Fundamental Research Funds for the Central Universities(Grant No.2015ZZ009)Guangdong Natural Science Funds for Distinguished Young Scholar(Grant No.2016A030306018)
文摘In this study, we developed a simple approach for the controllable growth of whitlockite （WH） on a β- tricalcium phosphate surface and investigated its cell viability via CCK-8, its live-dead staining and its alkaline phosphatase activity. Herein, WH with controllable morphologies was prepared by regulating the hydrothermal reaction conditions. The results of scanning electron microscopy, X-ray diffraction and X- ray photoelectron spectroscopy indicated that pure hexagonal plates of WH were prepared successfully. In vitro cell experiments showed that WH possessed excellent biocompatibility and effectively promoted the adhesion and proliferation of mouse bone mesenchymal stem cells. The osteogenesis of the WH was also enhanced. The obtained WH was expected to be utilized for promising applications as implantable block materials for bone repair.
文摘We investigate high-modulus degradable materials intended to replace metals in biomedical applications.These are typically composites comprising a polylactide(PLA)matrix reinforced with phosphate glass fibres,which provide reinforcement similar to E-glass but are entirely degradable in water to produce,principally,calcium phosphate.We have made composites using a variety of fibre architectures,from non-woven random mats to unidirectional fibre tapes.Flexural properties in the region of 30 GPa modulus and 350 MPa strength have been achieved-directly comparable to quoted values for human cortical bone.In collaboration with other groups we have begun to consider the development of foamed systems with structures mimicking cancellous bone and this has shown significant promise.The fibres in these foamed structures provide improved creep resistance and reinforcement of the pore walls.To date the materials have exhibited excellent cellular responses in vitro and further studies are due to include consideration of the surface character of the materials and the influence of this on cell interaction, both with the composites and the glass fibres themselves,which show promise as a standalone porous scaffold.
基金the financial support of the Brazilian National Research Council(CNPq)
文摘Doxycycline （DOX） exhibits anti-inflammatory and MMP inhibitory properties. The objectives of this study were to evaluate the effects of DOX on alveolar bone repair. Controls （CTL） and DOX-treated （10 and 25 mg. kg- 1） molars were extracted, and rats were killed 7 or 14 days later. The maxillae were processed and subjected to histological and immunohistochemical assays. Hematoxylin-eosin staining （7th day） revealed inflammation in the CTL group that was partly reversed after DOX treatment. On the 14th day, the CTL group exhibited bone neoformation, conjunctive tissue, re-epithelization and the absence of inflammatory infiltrate. DOX-treated groups exhibited complete re-epithelization, tissue remodelling and almost no inflammation. Picrosirius red staining in the DOXlO group （7th and 14th days） revealed an increased percentage of type I and III collagen fibres compared with the CTL and DOX25 groups. The DOXlO and DOX25 groups exhibited increases in osteoblasts on the 7th and 14th days. However, there were fewer osteoclasts in the DOXlO and DOX25 groups on the 7th and 14th days. Wnt-lOb- immunopositive cells increased by 130% and 150% on the 7th and 14th days, respectively, in DOX-treated groups compared with the CTL group. On the 7th day, Dickkopf （Dkk）-I immunostaining was decreased by 63% and 46% in the DOXlO and DOX25 groups, respectively. On the 14th day, 69% and 42% decreases in immunopositive cells were observed in the DOXlO and DOX25 groups, respectively, compared with the CTL group. By increasing osteoblasts, decreasing osteoclasts, activating Wnt lOb and neutralising Dkk, DOX is a potential candidate for bone repair in periodontal diseases.
文摘A new kind of nano-biomaterials of nano apatite （ NA ） and polyamide8063 （ PA ） composite was prepared by direct using NA slurry. The experimental results showed that the NA content in the composite was similar to that of natural bone. Interfrace chemical bonding was formed between NA and PA. The NA keeps the original morphological structure with a crystal size of 10- 30 nm in width by 50- 90 nm in length with a ratio of - 2.5 and distributed uniformly in thepolymer. The synthetic nano-biomaterials could be one of the best bioactive materials for load-bearing bone repair or substitution materials.
基金National Natural Science Foundation of China(No.82060347)Postgraduate innovation research project of Hainan Medical College(No.HYYS2020-38)。
文摘Objective:To prepare a bone repair material with certain mechanical strength and biological activity,this paper used calcium sulfate hemihydrate(CSH)powder compounded with calcium hydroxide(Ca(OH)2)powder to prepare a bone repair scaffold material for physicochemical property characterization and testing.Methods:The physical and chemical properties and characterization of the dried and cured bone repair materials were determined by Fourier infrared spectroscopy(FT-IR),X-ray diffraction(XRD),and scanning electron microscopy;Universal material testing machine to determine the mechanical and mechanical strength of composite materials.Results:XRD showed that the structure of the composite material phase at 5%concentration was calcium sulfate hemihydrate and calcium hydroxide after hydration.The FT-IR and XRD analyses were consistent.Scanning electron microscopy(SEM)results showed that calcium hydroxide was uniformly dispersed in the hemihydrate calcium sulfate material.0%,1%,5%,and 10%specimen groups had compressive strengths of 3.86±3.1,5.27±1.28,8.22±0.96,and 14.4±3.28 MPa.10%addition of calcium hydroxide significantly improved the mechanical strength of the composites,but also reduced the the porosity of the material.Conclusion:With the addition of calcium hydroxide,the CSH-Ca(OH)2 composite was improved in terms of mechanical material and is expected to be a new type of bone repair material.
文摘The extracellular matrix-associated bone morphogenetic proteins(BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed in many preclinical and clinical studies exploring their chondrogenic or osteoinductive potential in several animal model defects and in human diseases. During years of research in particular two BMPs, BMP2 and BMP7 have gained the podium for their use in the treatment of various cartilage and bone defects. In particular they have been recently approved for employment in non-union fractures as adjunct therapies. On the other hand, thanks to their potentialities in biomedical applications, there is a growing interest in studying the biology of mesenchymal stem cell(MSC), the rules underneath their differentiation abilities, and to test their true abilities in tissue engineering. In fact, the specific differentiation of MSCs into targeted celltype lineages for transplantation is a primary goal of the regenerative medicine. This review provides an overview on the current knowledge of BMP roles and signaling in MSC biology and differentiation capacities. In particular the article focuses on the potential clinical use of BMPs and MSCs concomitantly, in cartilage and bone tissue repair.
基金supported by the National Natural Science Foundation of China(81672166).
文摘Bone defect repair is a complex physiological process,starting with early modulation by the inflammatory im-mune system,and involves multiple physiological events,including angiogenesis,osteogenic differentiation,and mineralization.Biomaterial can regulate inflammatory responses through relevant immune cells in the local immune microenvironment of the implant-bone interface which is a hot topic in the field of regenerative medicine.Currently,Mg^(2+)regulates immune cells in the bone microenvironment to promote osteogenesis and angiogenesis mainly focuses on macrophages,but there is relatively little research on T cells.At the same time,the effective delivery and release of Mg^(2+)remains a challenge.To address these issues,we designed a new ther-mosensitive hyaluronic acid-hydroxypropyl chitin hydrogel(HPCH@HA)that has good affinity for Mg^(2+)and can sustained release it.In vitro,nano MgO loaded complex hydrogels effectively induced macrophage polarization from M0 phenotype to M2 phenotype and simultaneously activate T lymphocytes which also promoted human adipose-derived stem cells(hADSCs)osteogenic differentiation and mineralization and human umbilical vein endothelial cells(HUVECs)angiogenesis.In vivo,at the early stage of repair,the composite hydrogel has a good repair effect on mouse skull critical defect.All these results show that our designed composite hydrogels can effectively regulate the immune microenvironment of bone tissue and promoting the formation of mature bone in large bone defects and supporting in situ bone regeneration without the use of exogenous cells or inducers.It’s a promising candidate as immunomodulatory biomaterials for bone tissue engineering purposes.
基金National Natural Science Foundation of China(Nos.82102568,82172432)Guangdong Basic and Applied Basic Research Foundation(Nos.2022A1515220111,2022B1515120046,2021A1515220037,2022A1515220165)+4 种基金Shenzhen Key Medical Discipline Construction Fund(No.SZXK023)Shenzhen“San-Ming”Project of Medicine(No.SZSM202211038)Shenzhen Science and Technology Program(No.JCYJ20220818102815033,No.KCXFZ20201221173411031,No.JCYJ20210324110214040,No.JCYJ20210324105806016)The Scientific Research Foundation of PEKING UNIVERSITY SHENZHEN HOSPITAL(No.KYQD2021099)Shenzhen High-level Hospital Construction Fund.
文摘Bones can fulfill functions in movement,attachment,and protection of internal organs.Bone diseases caused by ageing,trauma,infection,and other reasons may seriously affect the daily life of patients.Magnesium ions are closely associated with the maintenance of bone health.Integrating magnesium ions into delivery systems and hydrogels can improve their application,thus directly acting on the osteoblast cell lineage and influencing the proliferation and differentiation of relevant cells.The slow release of magnesium ions allows for their effects on the target site for a long time,reducing the clearance of magnesium ions in the body,which significantly contributes to bone repair.Magnesium-based bioalloy scaffolds have received widespread attention for their favourable biocompatibility,degradability,and boneforming properties and play an important role in bone regeneration and repair.This article presents a review on the role and mechanism of magnesium-containing materials in bone repair and regeneration.By discussing the current challenges and future directions for magnesium-containing biomaterials,new insights are provided into the development of these materials in the field of orthopaedics.In conclusion,magnesium-containing biomaterials have great application value in orthopaedics.
基金the Key Project of the National Natural Science Foundation of China (No. 82030122&82474548)Sanming Project of Medicine in Shenzhen (No. SZZYSM202311020)。
文摘Background:Bushen Zhuanggu Formula(BZF),derived from the classic Yougui Pills,has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head(NONFH),particularly by promoting bone repair.However,its underlying mechanisms remain unclear.Objective:This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH.Materials and methods:A total of 518 potential BZF targets were identified from the ETCMv2.0 database.Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls.A drug target-disease gene interaction network was constructed to identify candidateBZF targets involved in NONFH pathogenesis.In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH.Results:Network analysis identified key pathways associated with blood circulation obstruction,immune-inflammatory imbalance,and abnormal bone metabolism.Protein kinase C alpha(PKCA),Ras proto-oncogene(RAS),mitogen-activated protein kinase 3(ERK),ETS proto-oncogene 1(ETS1),and receptor activator of nuclear factor-kB ligand(RANKL)formed a signaling axis implicated in NONFH pathogenesis.BZF treatment alleviated joint inflammation,preserved trabecular bone morphology,reduced bone loss,and promoted bone repair.Mechanistically,BZF significantly downregulated the expression of PKCA,RAS,ERK,ETS1,and RANKL,improved blood circulation,and inhibited osteoclast activation while promoting osteoblast activation.Conclusion:BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis,thereby reversing dysregulated bone metabolism.
基金This work was supported by Key Program of Natural Science Foundation of China(No.81930067)General Program of Nature Science Foundation of China(No.31870962)+2 种基金the Key Project of Logistics Research Plan of the PLA(No.AWS17J004-02-06)the Medical Science and Technology Youth Cultivation Project of PLA(No.20QNPY022)Medical innovation capability upgrading Plan of Southwest Hospital(No.SWH2018LJ-03).
文摘Endochondral bone formation is an important route for bone repair.Although emerging evidence has revealed the functions of long non-coding RNAs(lncRNAs)in bone and cartilage development,the effect of lncRNAs in endochondral bone repair is still largely unknown.Here,we identified a lncRNA,named Hypertrophic Chondrocyte Angiogenesis-related lncRNA(HCAR),and proved it to promote the endochondral bone repair by upregulating the expression of matrix metallopeptidase 13(Mmp13)and vascular endothelial growth factorα(Vegfa)in hypertrophic chondrocytes.Lnc-HCAR knockdown in hypertrophic chondrocytes restrained the cartilage matrix remodeling and decrease the CD31hiEmcnhi vessels number in a bone repair model.Mechanistically,we proved that lnc-HCAR was mainly enriched in the cytoplasm using fluorescence in situ hybridization(FISH)assay,and it acted as a molecular sponge for miR-15b-5p.Further,in hypertrophic chondrocytes,lnc-HCAR competitively bound to miR-15b-5p to increase Vegfa and Mmp13 expression.Our results proved that lncRNA is deeply involved in endochondral bone repair,which will provide a new theoretical basis for future strategies for promoting fracture healing.
基金National Key R&D Program of China(grant number 2022YFA1207500)National Natural Science Foundation of China(grant number 82072412).
文摘Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue engineering scaffolds is of great significance for bone repair.This study synthesized copper(Cu)-doped mesoporous silica nanoparticles(Cu@MSN)modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN(Cu@MSNMA).Furtheremore,bio-mimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution.This hydrogel achieves multi-modal bone tissue biomimicry:(ⅰ)GelMA/gelatin mimics the matrix components in bone ECM,ensuring biocompatibility while promoting cellular behavior(such as adhesion,proliferation,and differentiation);(ⅱ)GelMA/gela-tin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure,achieving structural and mechanical biomimicry to provide necessary support for bone defects;(ⅲ)The elemental biomimicry of Si and Cu in Cu@MSNMA achieves efficient osteogenic induction.The effect of different proportions of Cu@MSNMA on the physi-cal properties of the composite hydrogels was investigated to determine the optimal proportion.The results indicated that the mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio.Notably,5%NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel.In vitro and vivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition.In conclusion,the proposed nanocomposite hydrogel with biomimetic components and ion-regulating properties can serve as a multifunctional scaffold,offering antimicrobial properties for infected bone regeneration,and guide for future research in bone regeneration and three-dimensional printing.
基金supported by the National Key R&D Program of China(2021YFB3800900)National Natural Science Foundation of China(31971266,51232002)+1 种基金the Key Research and Development Program of Guangzhou(202007020002)Guangdong Province Basic and Applied Research Foundation(2022A1515011925).
文摘The process of bone repair is highly regulated by a large number of bioactive factors.Thus,a“cocktail”of bioactive factors supplemented to the defect sites is desirable for bone repair.In this regard,small extracellular vesicles(sEVs)derived from mesenchymal stem cells hold great potential in tissue repair.Nevertheless,the poor homing and retention of sEVs greatly limited their possible clinical application.In the present work,DMPE-PEG-CREKA was inserted into the membrane of sEVs released from adipose-derived mesenchymal stem cells to obtain CREKA functionalized sEVs(CREKA-sEVs),which could target fibrin to accumulate and retain in bone defects.Our results showed that CREKA-sEVs,like sEVs,promoted the osteogenic differentiation of BMSCs,the angiogenic property of HUVECs,and modulated the polarization of macrophages in vitro.Furthermore,due to the improved fibrin-binding and retention capacity of CREKA-sEVs,they enhanced the bone repair substantially in the rat femoral defect model.This study provided a new strategy to improve the therapeutic efficiency of sEVs and showed that CREKA-sEVs had great application value in bone tissue repair.
