Mandibular defects caused by injuries,tumors,and infections are common and can severely affect mandibular function and the patient's appearance.However,mandible reconstruction with a mandibular bionic structure re...Mandibular defects caused by injuries,tumors,and infections are common and can severely affect mandibular function and the patient's appearance.However,mandible reconstruction with a mandibular bionic structure remains challenging.Inspired by the process of intramembranous ossification in mandibular development,a hierarchical vascularized engineered bone consisting of angiogenesis and osteogenesis modules has been produced.Moreover,the hierarchical vascular network and bone structure generated by these hierarchical vascularized engineered bone modules match the particular anatomical structure of the mandible.The ultra-tough polyion complex has been used as the basic scaffold for hierarchical vascularized engineered bone for ensuring better reconstruction of mandible function.According to the results of in vivo experiments,the bone regenerated using hierarchical vascularized engineered bone is similar to the natural mandibular bone in terms of morphology and genomics.The sonic hedgehog signaling pathway is specifically activated in hierarchical vascularized engineered bone,indicating that the new bone in hierarchical vascularized engineered bone underwent a process of intramembranous ossification identical to that of mandible development.Thus,hierarchical vascularized engineered bone has a high potential for clinical application in mandibular defect reconstruction.Moreover,the concept based on developmental processes and bionic structures provides an effective strategy for tissue regeneration.展开更多
As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially ...As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially in the context of an imbalance between osteoblast and osteoclast activities.Therefore,the development of new biomaterials has become the key.This article reviews various design strategies and their advantages and disadvantages for biomaterials aimed at osteoporotic bone defects.Overall,current research progress indicates that innovative design,functionalization,and targeting of materials can significantly enhance bone regeneration under osteoporotic conditions.By comprehensively considering biocompatibility,mechanical properties,and bioactivity,these biomaterials can be further optimized,offering a range of choices and strategies for the repair of osteoporotic bone defects.展开更多
Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired b...Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired bone tissue.In recent years,strategies for the design and optimization of nanomaterials through thiolation modification have been widely applied in BTE.This review concisely summarizes the categories of nanomaterials commonly used in BTE and focuses on various strategies for the modification of nanomaterials via thiolation.A multifaceted analysis of the mechanisms by which thiolated nanomaterials enhance nanomaterial-cell interactions,promote drug loading and release,and modulate osteogenic differentiation is presented.Furthermore,this review introduces biomedical applications of thiolated nanomaterials in BTE,including as scaffold components for bone regeneration,coatings for bone implants,and drug delivery systems.Finally,the future perspectives and challenges in the development of this field are discussed.Thiolation modification strategies provide a platform for developing new ideas and methods for designing nanomaterials for BTE and are expected to accelerate the development and clinical translation of novel bone repair materials.展开更多
The field of bone tissue engineering has experienced an increase in prevalence due to the inherent challenge of the natural regeneration of significant bone deformities.This investigation focused on the preparation of...The field of bone tissue engineering has experienced an increase in prevalence due to the inherent challenge of the natural regeneration of significant bone deformities.This investigation focused on the preparation of Three-Dimensional(3D)-printed Polycaprolactone(PCL)scaffolds with varying proportions of Nanohydroxyapatite(NHA)and Nanoclay(NC),and their physiochemical and biological properties were assessed.The mechanical properties of PCL are satisfactory;however,its hydrophobic nature and long-term degradation hinder its use in scaffold fabrication.NHA and NC have been employed to improve the hydrophilic characteristics,mechanical strength,adhesive properties,biocompatibility,biodegradability,and osteoconductive behavior of PCL.The morphology results demonstrated 3D-printed structures with interconnected rectangular macropores and proper nanoparticle distribution.The sample containing 70 wt%NC showed the highest porosity(65.98±2.54%),leading to an increased degradation rate.The compressive strength ranged from 10.65±1.90 to 84.93±9.93 MPa,which is directly proportional to the compressive strength of cancellous bone(2–12 MPa).The wettability,water uptake,and biodegradability of PCL scaffolds considerably improved as the amount of NC increased.The results of the cellular assays exhibited increased proliferation,viability,and adhesion of MG-63 cells due to the addition of NHA and NC to the scaffolds.Finally,according to the in vitro results,it can be concluded that 3D-printed samples with higher amounts of NC can be regarded as a suitable scaffold for expediting the regeneration process of bone defects.展开更多
The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infan...The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infancy and there are significant challenges to overcome.In the modern era,the scientific community is increasingly turned to natural substances due to their superior biological ability,lower cost,biodegradability,and lower toxicity than synthetic lab-made products.Chitosan is a well-known polysaccharide that has recently garnered a high amount of attention for its biological activities,especially in 3D bone tissue engineering.Chitosan closely matches the native tissues and thus stands out as a popular candidate for bioprinting.This review focuses on the potential of chitosan-based scaffolds for advancements and the drawbacks in bone treatment.Chitosan-based nanocomposites have exhibited strong mechanical strength,water-trapping ability,cellular interaction,and biodegradability.Chitosan derivatives have also encouraged and provided different routes for treatment and enhanced biological activities.3D tailored bioprinting has opened new doors for designing and manufacturing scaffolds with biological,mechanical,and topographical properties.展开更多
Background We previously showed that nano-hydroxyapatite/carboxymethyl chitosan （n-Ha/CMCS） displayed excellent mechanical properties, good degradation rates and exceptional biocompatibility, with negligible toxicit...Background We previously showed that nano-hydroxyapatite/carboxymethyl chitosan （n-Ha/CMCS） displayed excellent mechanical properties, good degradation rates and exceptional biocompatibility, with negligible toxicity. The aim of this study was to determine the effect of the same composite with vascular endothelial growth factor （VEGF）transfected bone marrow stromal cells （BMSCs） in a rabbit radial defect model.展开更多
Background:Three-dimensional(3D)printed tissue engineered bone was used to repair the bone tissue defects in the oral and maxillofacial(OMF)region of experimental dogs.Material and methods:Canine bone marrow stromal c...Background:Three-dimensional(3D)printed tissue engineered bone was used to repair the bone tissue defects in the oral and maxillofacial(OMF)region of experimental dogs.Material and methods:Canine bone marrow stromal cells(BMSCs)were obtained from 9 male Beagle dogs and in vitro cultured for osteogenic differentiation.The OMF region was scanned for 3D printed surgical guide plate and mold by ProJet1200 high-precision printer using implant materials followed sintering at 1250℃.The tissue engineered bones was co-cultured with BASCs for 2 or 8 d.The cell scaffold composite was placed in the defects and fixed in 9 dogs in 3 groups.Postoperative CT and/or micro-CT scans were performed to observe the osteogenesis and material degradation.Results:BMSCs were cultured with osteogenic differentiation in the second generation(P2).The nanoporous hydroxyapatite implant was made using the 3D printing mold with the white porous structure and the hard texture.BMSCs with osteogenic induction were densely covered with the surface of the material after co-culture and ECM was secreted to form calcium-like crystal nodules.The effect of the tissue engineered bone on the in vivo osteogenesis ability was no significant difference between 2 d and 8 d of the compositing time.Conclusions:The tissue-engineered bone was constructed by 3D printing mold and hightemperature sintering to produce nanoporous hydroxyapatite scaffolds,which repair in situ bone defects in experimental dogs.The time of compositing for tissue engineered bone was reduced from 8 d to 2 d without the in vivo effect.展开更多
Nonunion represents a crucial challenge in orthopedic medicine,demanding innovative solutions beyond the scope of traditional bone grafting methods.Among the various strategies available,magnesium(Mg)implants have bee...Nonunion represents a crucial challenge in orthopedic medicine,demanding innovative solutions beyond the scope of traditional bone grafting methods.Among the various strategies available,magnesium(Mg)implants have been recognized for their biocompatibility and biodegradability.However,their susceptibility to rapid corrosion and degradation has garnered notable research interest in bone tissue engineering(BTE),particularly in the development of Mg-incorporated biocomposite scaffolds.These scaffolds gradually release Mg2+,which enhances immunomodulation,osteogenesis,and angiogenesis,thus facilitating effective bone regeneration.This review presents myriad fabrication techniques used to create Mg-incorporated biocomposite scaffolds,including electrospinning,three-dimensional printing,and sol-gel synthesis.Despite these advancements,the application of Mg-incorporated biocomposite scaffolds faces challenges such as controlling the degradation rate of Mg and ensuring mechanical stability.These limitations highlight the necessity for ongoing research aimed at refining fabrication techniques to better regulate the physicochemical and osteogenic properties of scaffolds.This review provides insights into the potential of Mg-incorporated biocomposite scaffolds for BTE and the challenges that need to be addressed for their successful translation into clinical applications.展开更多
In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we dev...In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.展开更多
Polycaprolactone(PCL)scaffolds that are produced through additive manufacturing are one of the most researched bone tissue engineering structures in the field.Due to the intrinsic limitations of PCL,carbon nanomateria...Polycaprolactone(PCL)scaffolds that are produced through additive manufacturing are one of the most researched bone tissue engineering structures in the field.Due to the intrinsic limitations of PCL,carbon nanomaterials are often investigated to reinforce the PCL scaffolds.Despite several studies that have been conducted on carbon nanomaterials,such as graphene(G)and graphene oxide(GO),certain challenges remain in terms of the precise design of the biological and nonbiological properties of the scaffolds.This paper addresses this limitation by investigating both the nonbiological(element composition,surface,degradation,and thermal and mechanical properties)and biological characteristics of carbon nanomaterial-reinforced PCL scaffolds for bone tissue engineering applications.Results showed that the incorporation of G and GO increased surface properties(reduced modulus and wettability),material crystallinity,crystallization temperature,and degradation rate.However,the variations in compressive modulus,strength,surface hardness,and cell metabolic activity strongly depended on the type of reinforcement.Finally,a series of phenomenological models were developed based on experimental results to describe the variations of scaffold’s weight,fiber diameter,porosity,and mechanical properties as functions of degradation time and carbon nanomaterial concentrations.The results presented in this paper enable the design of three-dimensional(3D)bone scaffolds with tuned properties by adjusting the type and concentration of different functional fillers.展开更多
With an elemental composition similar to bone mineral,and the ability to release phosphorus and calcium that benefit bone regeneration,Calcium Phosphate Glass(CPG)serves as a promising component of bone tissue enginee...With an elemental composition similar to bone mineral,and the ability to release phosphorus and calcium that benefit bone regeneration,Calcium Phosphate Glass(CPG)serves as a promising component of bone tissue engineering scaffolds.However,the degradation of CPG composites typically results in increased acidity,and its impact on bone-forming activity is less studied.In this work,we prepared 3D-printed composite scaffolds comprising CPG,Poly-ε-caprolactone(PCL),and various Magnesium Oxide(MgO)contents.Increasing the MgO content effectively suppressed the degradation of CPG,maintaining a physiological pH of the degradation media.While the degradation of CPG/PCL scaffolds resulted in upregulated apoptosis of Rat Bone Marrow-derived Stem Cells(rBMSC),scaffolds containing MgO were free from these negative impacts,and an optimal MgO content of 1 wt%led to the most pronounced osteogenic differentiation of rBMSCs.This work demonstrated that the rapid degradation of CPG impaired the renewability of stem cells through the increased acidity of the surrounding media,and MgO effectively modulated the degradation rate of CPG,thus preventing the negative effects of rapid degradation and supporting the proliferation and osteogenic differentiation of the stem cells.展开更多
BACKGROUND Stem cells from apical papilla(SCAPs)represent promising candidates for bone regenerative therapies due to their osteogenic potential.However,enhancing their differentiation capacity remains a critical chal...BACKGROUND Stem cells from apical papilla(SCAPs)represent promising candidates for bone regenerative therapies due to their osteogenic potential.However,enhancing their differentiation capacity remains a critical challenge.Enhancer of zeste homolog 2(EZH2),a histone H3 lysine 27 methyltransferase,regulates osteogenesis through epigenetic mechanisms,but its role in SCAPs remains unclear.We hypothesized that EZH2 modulates SCAP osteogenic differentiation via interaction with lysine demethylase 2B(KDM2B),offering a target for therapeutic intervention.AIM To investigate the functional role and molecular mechanism of EZH2 in SCAP osteogenic differentiation.METHODS SCAPs were isolated from healthy human third molars(n=6 donors).Osteogenic differentiation was assessed via Alizarin red staining and alkaline phosphatase assays.EZH2 overexpression/knockdown models were established using lentiviral vectors.Protein interactions were analyzed by co-immunoprecipitation,transcriptomic changes via microarray(Affymetrix platform),and chromatin binding by chromatin immunoprecipitation-quantitative polymerase chain reaction.In vivo bone formation was evaluated in immunodeficient mice(n=8/group)transplanted with SCAPs-hydroxyapatite scaffolds.Data were analyzed using Student’s t-test and ANOVA.RESULTS EZH2 overexpression increased osteogenic markers and mineralized nodule formation.In vivo,EZH2-overexpressing SCAPs generated 10%more bone/dentin-like tissue.Co-immunoprecipitation confirmed EZH2-KDM2B interaction,and peptide-mediated disruption of this binding enhanced osteogenesis.Transcriptome analysis identified 1648 differentially expressed genes(971 upregulated;677 downregulated),with pathway enrichment in Wnt/β-catenin signaling.CONCLUSION EZH2 promotes SCAP osteogenesis via antagonistic interaction with KDM2B,and targeted disruption of this axis offers a translatable strategy for bone regeneration.展开更多
The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical te...The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive （second generation） biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials （third generation） are designed to be not only osteo- conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer- ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental ＂origin＂ require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.展开更多
Three-dimensional honeycomb-structured magnesium （Mg） scaffolds with interconnected pores of accurately controlled pore size and porosity were fabricated by laser perforation technique. Biodegradable and bioactiveβ...Three-dimensional honeycomb-structured magnesium （Mg） scaffolds with interconnected pores of accurately controlled pore size and porosity were fabricated by laser perforation technique. Biodegradable and bioactiveβ- tricalcium phosphate （β-TCP） coatings were prepared on and the biodegradation mechanism was simply evaluated the porous Mg to further improve its biocompatibility, in vitro. It was found that the mechanical properties of this type of porous Mg significantly depended on its porosity. Elastic modulus and compressive strength similar to human bones could be obtained for the porous Mg with porosity of 42.6%-51%. It was observed that the human osteosarcoma cells （UMR106） were well adhered and proliferated on the surface of the β- TCP coated porous Mg, which indicates that theβ-TCP coated porous Mg is promising to be a bone tissue engineering scaffold material.展开更多
Bone organoids,which simulate and construct special organs in vitro with complex biological func-tions based on tissue engineering technology,provide dramatically realistic models for bone regenerative medicine develo...Bone organoids,which simulate and construct special organs in vitro with complex biological func-tions based on tissue engineering technology,provide dramatically realistic models for bone regenerative medicine development and lay the foundation for a new therapeutic strategy.The matrix microenviron-ment around tissues and cells plays a key role in the physiological functions and phenotypes of bone organoids.Traditionally,the commercially available Matrigel has been widely applied for organoid cul-tures.However,Matrigel is still facing challenges,including xenogenous origins and variable composi-tion.To address these issues,newly developed hydrogels become an appropriate candidate to alternate Matrigel for bone organoid culture.In this review,we summarized the development and limitations of ECM-based matrix(Matrigel)in the bone organoid cultures.Then we highlighted various hydrogel al-ternatives,including PEG,collagen,alginate,gelatin,chitosan,skin fibroin,and DNA derivative hydrogels,which have shown a promising application in bone tissue engineering and organoid cultures.Additionally,the effects of material properties(stiffness,viscoelasticity,charge,et al.)in hydrogels on cell culture and bone organoid culture were deeply investigated.Finally,we predicted that hydrogel-based biomaterials have a great potential for the construction and application of bone organoids.展开更多
Calcium phosphate cements （CPCs） are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports thei...Calcium phosphate cements （CPCs） are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports their increased application in bone tissue engineering. Much effort has been made to enhance the biological performance of CPCs, including their biocompatibility, osteoconductivity, osteoinductivity, biodegradability, bioactivity, and interactions with cells. This review article focuses on the major recent developments in CPCs, including 3D printing, injectability, stem cell delivery, growth factor and drug delivery, and pre- vascularization of CPC scaffolds via co-culture and tri-culture techniques to enhance angiogenesis and osteogenesis.展开更多
A new biomimetic bone tissue engineering scaffold material, nano-HAI PLGA-（ PEG-Asp ）n composite, was synthesized by a biologically inspired self-assembling approach. A novel biodegradable PLGA- （ PEG-Asp ）n cop...A new biomimetic bone tissue engineering scaffold material, nano-HAI PLGA-（ PEG-Asp ）n composite, was synthesized by a biologically inspired self-assembling approach. A novel biodegradable PLGA- （ PEG-Asp ）n copolymer with pendant amine functional groups and enhanced hydrophilicity woo synthesized by bulk ring-opening copolymerization by DL-lactide（ DLLA） and glycolide（ GA ） with Aspartic acid （ Asp ）-Polyethylene glycol（PEG） alt-prepolymer. A Three-dimensional, porous scaffold of the PLGA-（ PEG- Asp）n copolymer was fabricated by a solvent casting , particulate leaching process. The scaffold woo then incubated in modified simulated body fluid （naSBF）. Growth of HA nanocrystals on the inner pore surfaces of the porous scaffold is confirmed by calcium ion binding analyses, SEM , mass increooe meoourements and quantification of phosphate content within scaffolds. SEM analysis demonstrated the nucleation and growth of a continuous bonelike, low crystalline carbonated HA nanocrystals on the inner pore surfaces of the PLGA- （ PEG-Asp ）n scaffolds. The amount of calcium binding, total mass and the mass of phosphate on experimental PLGA- （ PEG-Asp ） n scaffolds at different incubation times in mSBF was significantly greater than that of control PLGA scaffolds. This nano-HA/ PLGA-（ PEG- Asp ）n composite stunts some features of natural bone both in main composition and hierarchical microstrueture. The Asp- PEG alt-prepolymer modified PleA copolymer provide a controllable high surface density and distribution of anionic functional groups which would enhance nucleation and growth of bonelike mineral following exposure to mSBF. This biomimetic treatment provides a simple method for surface functionalization and sabsequent mineral nucleation and self-oosembling on bodegradable polymer scaffolds for tissue engineering.展开更多
To investigate the osteoinductive and ectopicly osteogenic effects of a novel peptide P24 derived from bone morphogenetic protein 2 （BMP2）, biodegradable collagen scaffolds （CS） were used to load BMP-2-derived pep...To investigate the osteoinductive and ectopicly osteogenic effects of a novel peptide P24 derived from bone morphogenetic protein 2 （BMP2）, biodegradable collagen scaffolds （CS） were used to load BMP-2-derived peptide solutions with different concentrations （0.4 mg peptide/CS, 0.1 mg peptide/CS and pure CS, respectively）, and the implants were implanted into muscular pockets on the back of Wistar rats. Radiographs and histological analysis were performed to evaluate the ectopic bone effects. Active ectopic bone formation was seen in both groups containing the peptide at different concentration （0.4 mg and 0.1 mg）, whereas no bone formation and only fibrous tissue was seen in the pure CS group. The new bone formation induced by the peptide P24 displayed a dose-dependent and time-dependent efficiency. The new bone formation in the 0.4 mg peptide/CS group significantly increased than that of the 0.1 mg peptide/CS group. This novel BMP-2-derived peptide had excellent osteoinductive and ectopicly osteogenic properties which were similar to those of BMP2.展开更多
基金National Key Research and Development Program of China(2018YFA0703000)National Natural Science Foundation of China(8212200044,52075482,82071085,81873720)+2 种基金Zhejiang Provincial Natural Science Foundation of China(LR21H140001)Key Research and Development Program of Zhejiang,China(2017C01054,2018C03062)Scientific Research Fund of Zhejiang Provincial Education Department(Y202045564)。
文摘Mandibular defects caused by injuries,tumors,and infections are common and can severely affect mandibular function and the patient's appearance.However,mandible reconstruction with a mandibular bionic structure remains challenging.Inspired by the process of intramembranous ossification in mandibular development,a hierarchical vascularized engineered bone consisting of angiogenesis and osteogenesis modules has been produced.Moreover,the hierarchical vascular network and bone structure generated by these hierarchical vascularized engineered bone modules match the particular anatomical structure of the mandible.The ultra-tough polyion complex has been used as the basic scaffold for hierarchical vascularized engineered bone for ensuring better reconstruction of mandible function.According to the results of in vivo experiments,the bone regenerated using hierarchical vascularized engineered bone is similar to the natural mandibular bone in terms of morphology and genomics.The sonic hedgehog signaling pathway is specifically activated in hierarchical vascularized engineered bone,indicating that the new bone in hierarchical vascularized engineered bone underwent a process of intramembranous ossification identical to that of mandible development.Thus,hierarchical vascularized engineered bone has a high potential for clinical application in mandibular defect reconstruction.Moreover,the concept based on developmental processes and bionic structures provides an effective strategy for tissue regeneration.
基金supported by the National Natural Science Foundation of China(Nos.82160419 and 82302772)Guizhou Basic Research Project(No.ZK[2023]General 201)。
文摘As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially in the context of an imbalance between osteoblast and osteoclast activities.Therefore,the development of new biomaterials has become the key.This article reviews various design strategies and their advantages and disadvantages for biomaterials aimed at osteoporotic bone defects.Overall,current research progress indicates that innovative design,functionalization,and targeting of materials can significantly enhance bone regeneration under osteoporotic conditions.By comprehensively considering biocompatibility,mechanical properties,and bioactivity,these biomaterials can be further optimized,offering a range of choices and strategies for the repair of osteoporotic bone defects.
基金financially supported by the National Natural Science Foundation of China(Nos.52103184 and 8226030956)the National Key Research and Development Program of China(No.2022YFC2407503)+3 种基金Key Project of the Natural Science Basic Research Plan of Shaanxi Province(No.2022JZ43)Natural Science Basic Research Program of Shaanxi Province(No.2024JCYBQN-0874)Medical Research Key Project of Xi'an Science and Technology Bureau(No.2024JH-YXZD-0055)Medical Research Project of Xi'an Science and Technology Bureau(No.22YXYJ0083)
文摘Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired bone tissue.In recent years,strategies for the design and optimization of nanomaterials through thiolation modification have been widely applied in BTE.This review concisely summarizes the categories of nanomaterials commonly used in BTE and focuses on various strategies for the modification of nanomaterials via thiolation.A multifaceted analysis of the mechanisms by which thiolated nanomaterials enhance nanomaterial-cell interactions,promote drug loading and release,and modulate osteogenic differentiation is presented.Furthermore,this review introduces biomedical applications of thiolated nanomaterials in BTE,including as scaffold components for bone regeneration,coatings for bone implants,and drug delivery systems.Finally,the future perspectives and challenges in the development of this field are discussed.Thiolation modification strategies provide a platform for developing new ideas and methods for designing nanomaterials for BTE and are expected to accelerate the development and clinical translation of novel bone repair materials.
文摘The field of bone tissue engineering has experienced an increase in prevalence due to the inherent challenge of the natural regeneration of significant bone deformities.This investigation focused on the preparation of Three-Dimensional(3D)-printed Polycaprolactone(PCL)scaffolds with varying proportions of Nanohydroxyapatite(NHA)and Nanoclay(NC),and their physiochemical and biological properties were assessed.The mechanical properties of PCL are satisfactory;however,its hydrophobic nature and long-term degradation hinder its use in scaffold fabrication.NHA and NC have been employed to improve the hydrophilic characteristics,mechanical strength,adhesive properties,biocompatibility,biodegradability,and osteoconductive behavior of PCL.The morphology results demonstrated 3D-printed structures with interconnected rectangular macropores and proper nanoparticle distribution.The sample containing 70 wt%NC showed the highest porosity(65.98±2.54%),leading to an increased degradation rate.The compressive strength ranged from 10.65±1.90 to 84.93±9.93 MPa,which is directly proportional to the compressive strength of cancellous bone(2–12 MPa).The wettability,water uptake,and biodegradability of PCL scaffolds considerably improved as the amount of NC increased.The results of the cellular assays exhibited increased proliferation,viability,and adhesion of MG-63 cells due to the addition of NHA and NC to the scaffolds.Finally,according to the in vitro results,it can be concluded that 3D-printed samples with higher amounts of NC can be regarded as a suitable scaffold for expediting the regeneration process of bone defects.
文摘The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infancy and there are significant challenges to overcome.In the modern era,the scientific community is increasingly turned to natural substances due to their superior biological ability,lower cost,biodegradability,and lower toxicity than synthetic lab-made products.Chitosan is a well-known polysaccharide that has recently garnered a high amount of attention for its biological activities,especially in 3D bone tissue engineering.Chitosan closely matches the native tissues and thus stands out as a popular candidate for bioprinting.This review focuses on the potential of chitosan-based scaffolds for advancements and the drawbacks in bone treatment.Chitosan-based nanocomposites have exhibited strong mechanical strength,water-trapping ability,cellular interaction,and biodegradability.Chitosan derivatives have also encouraged and provided different routes for treatment and enhanced biological activities.3D tailored bioprinting has opened new doors for designing and manufacturing scaffolds with biological,mechanical,and topographical properties.
文摘Background We previously showed that nano-hydroxyapatite/carboxymethyl chitosan （n-Ha/CMCS） displayed excellent mechanical properties, good degradation rates and exceptional biocompatibility, with negligible toxicity. The aim of this study was to determine the effect of the same composite with vascular endothelial growth factor （VEGF）transfected bone marrow stromal cells （BMSCs） in a rabbit radial defect model.
基金The study was approved by the Animal Experimental Enthical Review From Of Southwest Medical University.Informed consent was obtained。
文摘Background:Three-dimensional(3D)printed tissue engineered bone was used to repair the bone tissue defects in the oral and maxillofacial(OMF)region of experimental dogs.Material and methods:Canine bone marrow stromal cells(BMSCs)were obtained from 9 male Beagle dogs and in vitro cultured for osteogenic differentiation.The OMF region was scanned for 3D printed surgical guide plate and mold by ProJet1200 high-precision printer using implant materials followed sintering at 1250℃.The tissue engineered bones was co-cultured with BASCs for 2 or 8 d.The cell scaffold composite was placed in the defects and fixed in 9 dogs in 3 groups.Postoperative CT and/or micro-CT scans were performed to observe the osteogenesis and material degradation.Results:BMSCs were cultured with osteogenic differentiation in the second generation(P2).The nanoporous hydroxyapatite implant was made using the 3D printing mold with the white porous structure and the hard texture.BMSCs with osteogenic induction were densely covered with the surface of the material after co-culture and ECM was secreted to form calcium-like crystal nodules.The effect of the tissue engineered bone on the in vivo osteogenesis ability was no significant difference between 2 d and 8 d of the compositing time.Conclusions:The tissue-engineered bone was constructed by 3D printing mold and hightemperature sintering to produce nanoporous hydroxyapatite scaffolds,which repair in situ bone defects in experimental dogs.The time of compositing for tissue engineered bone was reduced from 8 d to 2 d without the in vivo effect.
文摘Nonunion represents a crucial challenge in orthopedic medicine,demanding innovative solutions beyond the scope of traditional bone grafting methods.Among the various strategies available,magnesium(Mg)implants have been recognized for their biocompatibility and biodegradability.However,their susceptibility to rapid corrosion and degradation has garnered notable research interest in bone tissue engineering(BTE),particularly in the development of Mg-incorporated biocomposite scaffolds.These scaffolds gradually release Mg2+,which enhances immunomodulation,osteogenesis,and angiogenesis,thus facilitating effective bone regeneration.This review presents myriad fabrication techniques used to create Mg-incorporated biocomposite scaffolds,including electrospinning,three-dimensional printing,and sol-gel synthesis.Despite these advancements,the application of Mg-incorporated biocomposite scaffolds faces challenges such as controlling the degradation rate of Mg and ensuring mechanical stability.These limitations highlight the necessity for ongoing research aimed at refining fabrication techniques to better regulate the physicochemical and osteogenic properties of scaffolds.This review provides insights into the potential of Mg-incorporated biocomposite scaffolds for BTE and the challenges that need to be addressed for their successful translation into clinical applications.
基金supported by the National Key R&D Program of China[grant number 2021YFC2400700]the National Natural Science Foundation of China[grant numbers 82170929,81970908 and 81771039].
文摘In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.
基金The authors wish to acknowledge Engineering and Physical Sciences Research Council(EPSRC)UK for the Global Challenges Research Fund(No.EP/R015139/1)Rosetrees Trust UK&Stoneygate Trust UK for the Enterprise Fellowship(Ref:M874).
文摘Polycaprolactone(PCL)scaffolds that are produced through additive manufacturing are one of the most researched bone tissue engineering structures in the field.Due to the intrinsic limitations of PCL,carbon nanomaterials are often investigated to reinforce the PCL scaffolds.Despite several studies that have been conducted on carbon nanomaterials,such as graphene(G)and graphene oxide(GO),certain challenges remain in terms of the precise design of the biological and nonbiological properties of the scaffolds.This paper addresses this limitation by investigating both the nonbiological(element composition,surface,degradation,and thermal and mechanical properties)and biological characteristics of carbon nanomaterial-reinforced PCL scaffolds for bone tissue engineering applications.Results showed that the incorporation of G and GO increased surface properties(reduced modulus and wettability),material crystallinity,crystallization temperature,and degradation rate.However,the variations in compressive modulus,strength,surface hardness,and cell metabolic activity strongly depended on the type of reinforcement.Finally,a series of phenomenological models were developed based on experimental results to describe the variations of scaffold’s weight,fiber diameter,porosity,and mechanical properties as functions of degradation time and carbon nanomaterial concentrations.The results presented in this paper enable the design of three-dimensional(3D)bone scaffolds with tuned properties by adjusting the type and concentration of different functional fillers.
基金support from the National Key Research and Development Program of China(Grant No.2018YFA0703000)the National Natural Science Foundation of China(Grant Nos.52250006,52075482)+1 种基金the Ningbo Top Medical and Health Research Program(Grant No.2022020304)the Ningbo Key Science and Technology Major Project(Grant No.2022Z143).
文摘With an elemental composition similar to bone mineral,and the ability to release phosphorus and calcium that benefit bone regeneration,Calcium Phosphate Glass(CPG)serves as a promising component of bone tissue engineering scaffolds.However,the degradation of CPG composites typically results in increased acidity,and its impact on bone-forming activity is less studied.In this work,we prepared 3D-printed composite scaffolds comprising CPG,Poly-ε-caprolactone(PCL),and various Magnesium Oxide(MgO)contents.Increasing the MgO content effectively suppressed the degradation of CPG,maintaining a physiological pH of the degradation media.While the degradation of CPG/PCL scaffolds resulted in upregulated apoptosis of Rat Bone Marrow-derived Stem Cells(rBMSC),scaffolds containing MgO were free from these negative impacts,and an optimal MgO content of 1 wt%led to the most pronounced osteogenic differentiation of rBMSCs.This work demonstrated that the rapid degradation of CPG impaired the renewability of stem cells through the increased acidity of the surrounding media,and MgO effectively modulated the degradation rate of CPG,thus preventing the negative effects of rapid degradation and supporting the proliferation and osteogenic differentiation of the stem cells.
基金Supported by National Key Research and Development Program,No.2022YFA1104401Beijing Natural Science Foundation,No.7222075+1 种基金CAMS Innovation Fund for Medical Sciences,No.2019RU020Innovation Research Team Project of Beijing Stomatological Hospital,No.CXTD202204.
文摘BACKGROUND Stem cells from apical papilla(SCAPs)represent promising candidates for bone regenerative therapies due to their osteogenic potential.However,enhancing their differentiation capacity remains a critical challenge.Enhancer of zeste homolog 2(EZH2),a histone H3 lysine 27 methyltransferase,regulates osteogenesis through epigenetic mechanisms,but its role in SCAPs remains unclear.We hypothesized that EZH2 modulates SCAP osteogenic differentiation via interaction with lysine demethylase 2B(KDM2B),offering a target for therapeutic intervention.AIM To investigate the functional role and molecular mechanism of EZH2 in SCAP osteogenic differentiation.METHODS SCAPs were isolated from healthy human third molars(n=6 donors).Osteogenic differentiation was assessed via Alizarin red staining and alkaline phosphatase assays.EZH2 overexpression/knockdown models were established using lentiviral vectors.Protein interactions were analyzed by co-immunoprecipitation,transcriptomic changes via microarray(Affymetrix platform),and chromatin binding by chromatin immunoprecipitation-quantitative polymerase chain reaction.In vivo bone formation was evaluated in immunodeficient mice(n=8/group)transplanted with SCAPs-hydroxyapatite scaffolds.Data were analyzed using Student’s t-test and ANOVA.RESULTS EZH2 overexpression increased osteogenic markers and mineralized nodule formation.In vivo,EZH2-overexpressing SCAPs generated 10%more bone/dentin-like tissue.Co-immunoprecipitation confirmed EZH2-KDM2B interaction,and peptide-mediated disruption of this binding enhanced osteogenesis.Transcriptome analysis identified 1648 differentially expressed genes(971 upregulated;677 downregulated),with pathway enrichment in Wnt/β-catenin signaling.CONCLUSION EZH2 promotes SCAP osteogenesis via antagonistic interaction with KDM2B,and targeted disruption of this axis offers a translatable strategy for bone regeneration.
文摘The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive （second generation） biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials （third generation） are designed to be not only osteo- conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer- ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental ＂origin＂ require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.
基金supported by Chinese Academy of Sciences (The Applied Research of Bioactive Bone Implantation Materials, No. KGCX2-YW-207)
文摘Three-dimensional honeycomb-structured magnesium （Mg） scaffolds with interconnected pores of accurately controlled pore size and porosity were fabricated by laser perforation technique. Biodegradable and bioactiveβ- tricalcium phosphate （β-TCP） coatings were prepared on and the biodegradation mechanism was simply evaluated the porous Mg to further improve its biocompatibility, in vitro. It was found that the mechanical properties of this type of porous Mg significantly depended on its porosity. Elastic modulus and compressive strength similar to human bones could be obtained for the porous Mg with porosity of 42.6%-51%. It was observed that the human osteosarcoma cells （UMR106） were well adhered and proliferated on the surface of the β- TCP coated porous Mg, which indicates that theβ-TCP coated porous Mg is promising to be a bone tissue engineering scaffold material.
基金This work was funded by the National Key R&D Program of China(No.2018YFC2001500)the National Natural Science Foun-dation of China(Nos.82172098,82001968)Shanghai Pujiang Program(No.20PJ1403800).
文摘Bone organoids,which simulate and construct special organs in vitro with complex biological func-tions based on tissue engineering technology,provide dramatically realistic models for bone regenerative medicine development and lay the foundation for a new therapeutic strategy.The matrix microenviron-ment around tissues and cells plays a key role in the physiological functions and phenotypes of bone organoids.Traditionally,the commercially available Matrigel has been widely applied for organoid cul-tures.However,Matrigel is still facing challenges,including xenogenous origins and variable composi-tion.To address these issues,newly developed hydrogels become an appropriate candidate to alternate Matrigel for bone organoid culture.In this review,we summarized the development and limitations of ECM-based matrix(Matrigel)in the bone organoid cultures.Then we highlighted various hydrogel al-ternatives,including PEG,collagen,alginate,gelatin,chitosan,skin fibroin,and DNA derivative hydrogels,which have shown a promising application in bone tissue engineering and organoid cultures.Additionally,the effects of material properties(stiffness,viscoelasticity,charge,et al.)in hydrogels on cell culture and bone organoid culture were deeply investigated.Finally,we predicted that hydrogel-based biomaterials have a great potential for the construction and application of bone organoids.
基金supported by NIH R01 DE14190 and R21 DE22625(HX)the National Science Foundation of China 81401794(PW)and 81400487(LW)+2 种基金the Youth Fund of Science and Technology of Jilin Province 20150520043JH(LW)the China Postdoctoral Science Foundation 2015M581405(LW)the University of Maryland School of Dentistry bridge fund(HX)
文摘Calcium phosphate cements （CPCs） are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports their increased application in bone tissue engineering. Much effort has been made to enhance the biological performance of CPCs, including their biocompatibility, osteoconductivity, osteoinductivity, biodegradability, bioactivity, and interactions with cells. This review article focuses on the major recent developments in CPCs, including 3D printing, injectability, stem cell delivery, growth factor and drug delivery, and pre- vascularization of CPC scaffolds via co-culture and tri-culture techniques to enhance angiogenesis and osteogenesis.
文摘A new biomimetic bone tissue engineering scaffold material, nano-HAI PLGA-（ PEG-Asp ）n composite, was synthesized by a biologically inspired self-assembling approach. A novel biodegradable PLGA- （ PEG-Asp ）n copolymer with pendant amine functional groups and enhanced hydrophilicity woo synthesized by bulk ring-opening copolymerization by DL-lactide（ DLLA） and glycolide（ GA ） with Aspartic acid （ Asp ）-Polyethylene glycol（PEG） alt-prepolymer. A Three-dimensional, porous scaffold of the PLGA-（ PEG- Asp）n copolymer was fabricated by a solvent casting , particulate leaching process. The scaffold woo then incubated in modified simulated body fluid （naSBF）. Growth of HA nanocrystals on the inner pore surfaces of the porous scaffold is confirmed by calcium ion binding analyses, SEM , mass increooe meoourements and quantification of phosphate content within scaffolds. SEM analysis demonstrated the nucleation and growth of a continuous bonelike, low crystalline carbonated HA nanocrystals on the inner pore surfaces of the PLGA- （ PEG-Asp ）n scaffolds. The amount of calcium binding, total mass and the mass of phosphate on experimental PLGA- （ PEG-Asp ） n scaffolds at different incubation times in mSBF was significantly greater than that of control PLGA scaffolds. This nano-HA/ PLGA-（ PEG- Asp ）n composite stunts some features of natural bone both in main composition and hierarchical microstrueture. The Asp- PEG alt-prepolymer modified PleA copolymer provide a controllable high surface density and distribution of anionic functional groups which would enhance nucleation and growth of bonelike mineral following exposure to mSBF. This biomimetic treatment provides a simple method for surface functionalization and sabsequent mineral nucleation and self-oosembling on bodegradable polymer scaffolds for tissue engineering.
基金the National Natural Science Foundation of China(No.30200063,30070483,301070270)the Program for New Century Excellent Talents in University from the Ministry of Education of China,and the Excellent Youth Foundation of Wuhan Science and Technology Committee(No.20005006071-10)
文摘To investigate the osteoinductive and ectopicly osteogenic effects of a novel peptide P24 derived from bone morphogenetic protein 2 （BMP2）, biodegradable collagen scaffolds （CS） were used to load BMP-2-derived peptide solutions with different concentrations （0.4 mg peptide/CS, 0.1 mg peptide/CS and pure CS, respectively）, and the implants were implanted into muscular pockets on the back of Wistar rats. Radiographs and histological analysis were performed to evaluate the ectopic bone effects. Active ectopic bone formation was seen in both groups containing the peptide at different concentration （0.4 mg and 0.1 mg）, whereas no bone formation and only fibrous tissue was seen in the pure CS group. The new bone formation induced by the peptide P24 displayed a dose-dependent and time-dependent efficiency. The new bone formation in the 0.4 mg peptide/CS group significantly increased than that of the 0.1 mg peptide/CS group. This novel BMP-2-derived peptide had excellent osteoinductive and ectopicly osteogenic properties which were similar to those of BMP2.
