Bone defects,characterized by a loss of skeletal structure integrity,represent a prevalent clinical challenge affecting millions of patients.While bone autografts and allografts offer potential solutions,limitations,i...Bone defects,characterized by a loss of skeletal structure integrity,represent a prevalent clinical challenge affecting millions of patients.While bone autografts and allografts offer potential solutions,limitations,including donor scarcity,immune rejection,anatomical constraints,and complications arising from host comorbidities such as diabetes,often lead to unsatisfactory outcomes.This necessitates the need for alternative treatments.Researchers have identified that reactive oxygen species(ROS)play a crucial role in bone regeneration.Although physiological ROS levels are essential for normal healing,excessive ROS accumulation disrupts the balance between bone formation and resorption,hindering regeneration.Antioxidants can mitigate oxidative stress by scavenging ROS or inhibiting their formation,thereby restoring the equilibrium between bone formation and resorption.Advances in nanotechnology have enabled the development of various ROS-scavenging nanomaterials with enhanced therapeutic efficacy.These nanomaterials either function as delivery platforms for conventional antioxidants or as direct ROS-neutralizing agents through intrinsic redox or enzyme-mimicking properties.This review comprehensively summarizes ROS-scavenging nanomaterials for bone tissue regeneration,focusing on their design strategies,underlying mechanisms,applications,and potential for clinical translation.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
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
This review article presents a comprehensive overview of emerging technologies in bone tissue engineering(BTE).This rapidly advancing field addresses the challenges of bone defects and injuries beyond traditional trea...This review article presents a comprehensive overview of emerging technologies in bone tissue engineering(BTE).This rapidly advancing field addresses the challenges of bone defects and injuries beyond traditional treatments like autografts and allografts.The study highlights the integration of 3D bioprinting,stem cell therapy,gene therapy,biomaterials,nanotechnology,and computational modeling as transformative approaches in BTE.Developing biomimetic scaffolds,advanced bio-inks,and composite nanomaterials has enhanced seaffold design,improving mechanical properties and biocompatibility.Innovatiohs in gene therapy and bioactive molecule delivery are showcased for their ability to modulate cellular behavior and enhance osteogenesis.Stem cell-based therapies leverage the regenerative potential of mesenchymal stem cells,facilitating tissue integration and functional restoration.Computational tools,including finite element analysis(FEA)and agent-based modelling,aid in the optimization of scaffold design,predicting mechanical responses and biological behaviors.Despite notable progress,signifieant challenges,such as achieving reliable vascularization,sealable manu-facturing of engineered constructs,and effective clinical translation,remain substantial barriers to widespread adoption.Future research efforts focused on refining these technologies are vital for translating innovative strategies into elinical practice,paving the way for personalized regenerative solutions in bone repair.展开更多
Nanofiber scaffold has built a bionic microenvironment for bone marrow mesenchymal stem cells by highly simulating the topological structure of natural extracellular matrix.Its ordered fiber network effectively guides...Nanofiber scaffold has built a bionic microenvironment for bone marrow mesenchymal stem cells by highly simulating the topological structure of natural extracellular matrix.Its ordered fiber network effectively guides the directional migration and spatial arrangement of cells through the mechanical signal transduction mediated by integrin.Surface functionalization can synergistically activate the osteogenic transcription network and significantly enhance the osteogenic differentiation potential of cells.The precise design of scaffold stiffness affects the cell fate choice by regulating the nuclear translocation of mechanical sensitive factors.This triple cooperative strategy of“physical topology-biochemical signal-mechanical microenvironment”effectively overcomes the biological inertia of traditional scaffolds and provides a dynamic and adjustable platform for bone defect repair.Looking forward to the future,breaking through the bottleneck of clinical transformation such as long-term intelligent slow release of functional factors and in situ efficient construction of vascular network is the key to promoting nanofiber scaffolds from basic research to precise bone regeneration treatment.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
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
The biocompatibility and osteogenic activity of allogenic decalcified bone matrix (DBM) used as a carrier for bone tissue engineering were studied. Following the method described by Urist, allogenic DBM was made. In v...The biocompatibility and osteogenic activity of allogenic decalcified bone matrix (DBM) used as a carrier for bone tissue engineering were studied. Following the method described by Urist, allogenic DBM was made. In vitro, DBM and bone marrow stromal cell (BMSC) from rabbits were co-cultured for 3-7 days and subjected to HE staining, and a series of histomorphological observations were performed under phase-contrast microscopy and scanning electron microscopy (SEM). In vivo the mixture of DBM/BMSC co-cultured for 3 days was planted into one side of muscules sacrospinalis of rabbits, and the DBM without BMSC was planted into other side as control. Specimens were collected at postoperative week 1, 2 and 4, and subjected to HE staining, and observed under SEM. The results showed during culture in vitro, the BMSCs adherent to the wall of DBM grew, proliferated and had secretive activity. The in vivo experiment revealed that BMSCs and undifferentiated mesenchymal cells in the perivascular region invaded gradually and proliferated together in DBM/BMSC group, and colony-forming units of chondrocytes were found. Osteoblasts, trabecular bone and medullary cavity appeared. The inflammatory reaction around muscles almost disappeared at the second weeks. In pure DBM group, the similar changes appeared from the surface of the DBM to center, and the volume of total regenerate bones was less than the DBM/BMSC group at the same time. The results indicated that the mixture of DBM and BMSC had good biocompatibility and ectopic induced osteogenic activity.展开更多
Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate （CAP） biomaterials/scaffolds are of special interest as they share chemical/crystallographic simila...Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate （CAP） biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review： nanostructured calcium phosphate cement （CPC）; nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/ morphology, differentiation and in vivo bone regeneration. Several trends can be seen： （i） nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; （ii） the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; （iii） nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; （iv） combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and （v） cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.展开更多
Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration,blood vessels invasion and transport of nutrient and waste.However,efforts and understanding of the interconnec...Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration,blood vessels invasion and transport of nutrient and waste.However,efforts and understanding of the interconnectivity of porous Mg is limited due to the diverse architectures of pore struts and pore size distribution of Mg scaffold systems.In this work,biomimetic hierarchical porous Mg scaffolds with tailored interconnectivity as well as pore size distribution were prepared by template replication of infiltration casting.Mg scaffold with better interconnectivity showed lower mechanical strength.Enlarging interconnected pores would enhance the interconnectivity of the whole scaffold and reduce the change of ion concentration,pH value and osmolality of the degradation microenvironment due to the lower specific surface area.Nevertheless,the degradation rates of five tested Mg scaffolds were no different because of the same geometry of strut unit.Direct cell culture and evaluation of cell density at both sides of four typical Mg scaffolds indicated that cell migration through hierarchical porous Mg scaffolds could be enhanced by not only bigger interconnected pore size but also larger main pore size.In summary,design of interconnectivity in terms of pore size distribution could regulate mechanical strength,microenvironment in cell culture condition and cell migration potential,and beyond that it shows great potential for personalized therapy which could facilitate the regeneration process.展开更多
In this paper, preparation of nano-biphasic calcium phosphate （nBCP）, mechanical behavior and load-bearing of poly （lactide-co-glycolide） （PLGA） and PLGA/nBCP are presented. The nBCP with composition of 63/37 （...In this paper, preparation of nano-biphasic calcium phosphate （nBCP）, mechanical behavior and load-bearing of poly （lactide-co-glycolide） （PLGA） and PLGA/nBCP are presented. The nBCP with composition of 63/37 （w/w） HA/-TCP （hydroxyapatite/fl-tricalcium phosphate） was produced by heating of bovine bone at 700℃. Composite scaffolds were made by using PLGA matrix and 10-50 wt% nBCP powders as reinforcement material. All scaffolds were prepared by thermally induced solid-liquid phase separation （TIPS） at -60~C under 4 Pa （0.04 mbar） vacuum. The results of elastic modulus testing were adjusted with Ishai-Cohen and Narkis models for rigid polymeric matrix and compared to each other. PLGA/nBCP scaffolds with 30 wt% nBCP showed the highest value of yield strength among the scaffolds. In addition, it was found that by increasing the nBCP in scaffolds to 50 wt%, the modulus of elasticity was highly enhanced. However, the optimum value of yield strength was obtained at 30 wt% nBCP, and the agglomeration of reinforcing particles at higher percentages caused a reduction in yield strength. It is clear that the elastic modulus of matrix has the significant role in elastic modulus of scaffolds, as also the size of the filler particles in the matrix.展开更多
The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing ...The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor （VDR）, we examined their response to different concentrations of 25-hydroxy vitamin D3 [25（OH）D3] （100 or 500 nmol·L^-1） and 1,25-dihydroxy vitamin D3 [1,25（OH）2D3] （0.1 or 0.5 nmol·L^-1） metabolites in cell cultures. Specifically, CD14＋ monocytes were cultured in charcoal-stripped serum in the presence of receptor activator of nuclear factor kappa-B ligand （RANKL） and macrophage colony-stimulating factor （M-CSF）. Tartrate-resistant acid phosphatase （TRAP） histochemical staining assays and dentine resorption analysis were used to identify the size and number of osteoclast cells, number of nuclei per cell and resorption activity. The expression of VDR was detected in human bone tissue （ex vivo） by immunohistochemistry and in vitro cell cultures by western blotting. Quantitative reverse transcription-PCR （qRT-PCR） was used to determine the level of expression of vitamin D-related genes in response to vitamin D metabolites. VDR-related genes during osteoclastogenesis, shown by qRT-PCR, was stimulated in response to 500 nmol·L^-1 of 25（OH）D3 and 0.1-0.5 nmol·L^-1 of 1,25（OH）2D3, upregulating cytochrome P450 family 27 subfamily B member I （CYP27B1） and cytochrome P450 family 24 subfamily A member I （CYP24A1）. Osteoclast fusion transcripts transmembrane 7 subfamily member 4 （tm7sf4） and nuclear factor of activated T-cell cytoplasmic 1 （nfatcl） where downregulated in response to vitamin D metabolites. Osteoclast number and resorption activity were also increased. Both 25（OH）D3 and 1,25（OH）2D3 reduced osteoclast size and number when co-treated with RANKL and M-CSF. The evidence for VDR expression in resorbing osteoclasts in vivo and low-dose effects of 1,25（OH）2D3 on osteoclasts in vitro may therefore provide insight into the effects of clinical vitamin D treatments, further providing a counterpoint to the high-dose effects reported from in vitro experiments.展开更多
Lanthanum(La)has tremendous potential in the treatment and prevention of bone diseases especially osteoporosis and metabolic disorders.However,controlling its distribution and keeping the release of La^(3+)ions sustai...Lanthanum(La)has tremendous potential in the treatment and prevention of bone diseases especially osteoporosis and metabolic disorders.However,controlling its distribution and keeping the release of La^(3+)ions sustained and steady in the body is still a big challenge.In this study,we prepared La-OCP powders via co-precipitation method,and further prepared La-OCP/PLA porous scaffolds by 3 D printing.La^(3+)was successfully introduced into the OCP crystal structure and substituted Ca^(2+)at the Ca-5 and Ca-8 sites.In particular,some La^(3+)ions were deposited on the crystal surface in the form of nanoparticles.Both octacalcium phosphate(OCP,Ca_(8)H_(2)(PO_(4))_6·5 H_(2)O)crystals and nanoparticles played as the carriers for La^(3+)ions.The La-OCP/PLA scaffolds displayed obvious mineralization effects and sustained release of La^(3+).The scaffolds contained a uniform structure with rough micro surface topography which acted as a suitable pathway for BMSCs cells to adhere,grow and proliferation.At a certain La^(3+)concentration,the extracts from La-OCP/PLA scaffolds increased the expression of osteogenesis-related genes,thus promoting the osteogenic differentiation of BMSCs.Moreover,the extracts regulated the immune responses.The experiment in vivo proved that La-OCP/PLA porous scaffolds were safe and could enhance bone defect regeneration in vivo.These findings suggest that 3 D printed La-OCP/PLA porous scaffolds have promising potentials in bone tissue engineering.展开更多
Bone tissue engineering(BTE)has proven to be a promising strategy for bone defect repair.Due to its excellent biological properties,gelatin methacrylate(GelMA)hydrogels have been used as bioinks for 3D bioprinting in ...Bone tissue engineering(BTE)has proven to be a promising strategy for bone defect repair.Due to its excellent biological properties,gelatin methacrylate(GelMA)hydrogels have been used as bioinks for 3D bioprinting in some BTE studies to produce scaffolds for bone regeneration.However,applications for load-bearing defects are limited by poor mechanical properties and a lack of bioactivity.In this study,3D printing technology was used to create nano-attapulgite(nano-ATP)/GelMA composite hydrogels loaded into mouse bone mesenchymal stem cells(BMSCs)and mouse umbilical vein endothelial cells(MUVECs).The bioprintability,physicochemical properties,and mechanical properties were all thoroughly evaluated.Our findings showed that nano-ATP groups outperform the control group in terms of printability,indicating that nano-ATP is beneficial for printability.Additionally,after incorporation with nano-ATP,the mechanical strength of the composite hydrogels was significantly improved,resulting in adequate mechanical properties for bone regeneration.The presence of nano-ATP in the scaffolds has also been stud-ied for cell-material interactions.The findings show that cells within the scaffold not only have high viability but also a clear proclivity to promote osteogenic differentiation of BMSCs.Besides,the MUVECs-loaded composite hydrogels demonstrated increased angiogenic activity.A cranial defect model was also developed to evaluate the bone repair capability of scaffolds loaded with rat BMSCs.According to histo-logical analysis,cell-laden nano-ATP composite hydrogels can effectively im prove bone regeneration and promote angiogenesis.This study demonstrated the potential of nano-ATP for bone tissue engineering,which should also increase the clinical practicality of nano-ATP.展开更多
The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bon...The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.展开更多
Metal-organic frameworks(MOFs), a class of hybrid materials, consist of organic linkers and bridging metal ions or clusters. Their tunable pore sizes, large surface area, good biocompatibility, structural variability ...Metal-organic frameworks(MOFs), a class of hybrid materials, consist of organic linkers and bridging metal ions or clusters. Their tunable pore sizes, large surface area, good biocompatibility, structural variability in combination with materials and chemicals, and osteogenic effects provide potential approaches for bone tissue engineering and bone diseases. And there are more and more research on MOFs in the field of osteogenesis in recent years. This review presents an overall summary of the application in the bone tissue engineering and bone diseases of MOFs and their composites, starting with the synthesis of MOFs, which discusses the advantages and disadvantages of different syntheses. Then, the biological functions of MOFs are discussed, which are the basics of MOFs applied in the organism. Importantly,mechanisms and abundant applications of MOFs are detailed in the bone tissue engineering and bone diseases. Finally, some prospects of MOFs are discussed, for instance, exploring whether MOFs can be used to treat other bone diseases.展开更多
Bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction.Autografts and allografts have been used in clinical application for some time,but they have disadvantage...Bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction.Autografts and allografts have been used in clinical application for some time,but they have disadvantages.With the inherent drawback in the precision and reproducibility of conventional scaffold fabrication techniques,the results of bone surgery may not be ideal.This is despite the introduction of bone tissue engineering which provides a powerful approach for bone repair.Rapid prototyping technologies have emerged as an alternative and have been widely used in bone tissue engineering,enhancing bone tissue regeneration in terms of mechanical strength,pore geometry,and bioactive factors,and overcoming some of the disadvantages of conventional technologies.This review focuses on the basic principles and characteristics of various fabrication technologies,such as stereolithography,selective laser sintering,and fused deposition modeling,and reviews the application of rapid prototyping techniques to scaffolds for bone tissue engineering.In the near future,the use of scaffolds for bone tissue engineering prepared by rapid prototyping technology might be an effective therapeutic strategy for bone defects.展开更多
基金supported by the National Natural Science Foundation of China(No.82371102,China)the Key program of Shanghai Science and Technology Commission(No.23JC1402400,China).
文摘Bone defects,characterized by a loss of skeletal structure integrity,represent a prevalent clinical challenge affecting millions of patients.While bone autografts and allografts offer potential solutions,limitations,including donor scarcity,immune rejection,anatomical constraints,and complications arising from host comorbidities such as diabetes,often lead to unsatisfactory outcomes.This necessitates the need for alternative treatments.Researchers have identified that reactive oxygen species(ROS)play a crucial role in bone regeneration.Although physiological ROS levels are essential for normal healing,excessive ROS accumulation disrupts the balance between bone formation and resorption,hindering regeneration.Antioxidants can mitigate oxidative stress by scavenging ROS or inhibiting their formation,thereby restoring the equilibrium between bone formation and resorption.Advances in nanotechnology have enabled the development of various ROS-scavenging nanomaterials with enhanced therapeutic efficacy.These nanomaterials either function as delivery platforms for conventional antioxidants or as direct ROS-neutralizing agents through intrinsic redox or enzyme-mimicking properties.This review comprehensively summarizes ROS-scavenging nanomaterials for bone tissue regeneration,focusing on their design strategies,underlying mechanisms,applications,and potential for clinical translation.
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.
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.
基金the Deanship of Scientific Research at King Khalid University for funding this study through the Large Research Group Project under grant number"RGP 2/365/45".
文摘This review article presents a comprehensive overview of emerging technologies in bone tissue engineering(BTE).This rapidly advancing field addresses the challenges of bone defects and injuries beyond traditional treatments like autografts and allografts.The study highlights the integration of 3D bioprinting,stem cell therapy,gene therapy,biomaterials,nanotechnology,and computational modeling as transformative approaches in BTE.Developing biomimetic scaffolds,advanced bio-inks,and composite nanomaterials has enhanced seaffold design,improving mechanical properties and biocompatibility.Innovatiohs in gene therapy and bioactive molecule delivery are showcased for their ability to modulate cellular behavior and enhance osteogenesis.Stem cell-based therapies leverage the regenerative potential of mesenchymal stem cells,facilitating tissue integration and functional restoration.Computational tools,including finite element analysis(FEA)and agent-based modelling,aid in the optimization of scaffold design,predicting mechanical responses and biological behaviors.Despite notable progress,signifieant challenges,such as achieving reliable vascularization,sealable manu-facturing of engineered constructs,and effective clinical translation,remain substantial barriers to widespread adoption.Future research efforts focused on refining these technologies are vital for translating innovative strategies into elinical practice,paving the way for personalized regenerative solutions in bone repair.
文摘Nanofiber scaffold has built a bionic microenvironment for bone marrow mesenchymal stem cells by highly simulating the topological structure of natural extracellular matrix.Its ordered fiber network effectively guides the directional migration and spatial arrangement of cells through the mechanical signal transduction mediated by integrin.Surface functionalization can synergistically activate the osteogenic transcription network and significantly enhance the osteogenic differentiation potential of cells.The precise design of scaffold stiffness affects the cell fate choice by regulating the nuclear translocation of mechanical sensitive factors.This triple cooperative strategy of“physical topology-biochemical signal-mechanical microenvironment”effectively overcomes the biological inertia of traditional scaffolds and provides a dynamic and adjustable platform for bone defect repair.Looking forward to the future,breaking through the bottleneck of clinical transformation such as long-term intelligent slow release of functional factors and in situ efficient construction of vascular network is the key to promoting nanofiber scaffolds from basic research to precise bone regeneration treatment.
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.
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.
文摘The biocompatibility and osteogenic activity of allogenic decalcified bone matrix (DBM) used as a carrier for bone tissue engineering were studied. Following the method described by Urist, allogenic DBM was made. In vitro, DBM and bone marrow stromal cell (BMSC) from rabbits were co-cultured for 3-7 days and subjected to HE staining, and a series of histomorphological observations were performed under phase-contrast microscopy and scanning electron microscopy (SEM). In vivo the mixture of DBM/BMSC co-cultured for 3 days was planted into one side of muscules sacrospinalis of rabbits, and the DBM without BMSC was planted into other side as control. Specimens were collected at postoperative week 1, 2 and 4, and subjected to HE staining, and observed under SEM. The results showed during culture in vitro, the BMSCs adherent to the wall of DBM grew, proliferated and had secretive activity. The in vivo experiment revealed that BMSCs and undifferentiated mesenchymal cells in the perivascular region invaded gradually and proliferated together in DBM/BMSC group, and colony-forming units of chondrocytes were found. Osteoblasts, trabecular bone and medullary cavity appeared. The inflammatory reaction around muscles almost disappeared at the second weeks. In pure DBM group, the similar changes appeared from the surface of the DBM to center, and the volume of total regenerate bones was less than the DBM/BMSC group at the same time. The results indicated that the mixture of DBM and BMSC had good biocompatibility and ectopic induced osteogenic activity.
基金supported by NIH R01 DE14190 and R21 DE22625 (HX)National Science Foundation of China 31100695 and 31328008 (LZ), 81401794 (PW)Maryland Stem Cell Research Fund and University of Maryland School of Dentistry
文摘Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate （CAP） biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review： nanostructured calcium phosphate cement （CPC）; nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/ morphology, differentiation and in vivo bone regeneration. Several trends can be seen： （i） nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; （ii） the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; （iii） nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; （iv） combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and （v） cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.
基金supported by grants from Shenzhen Key Medical Subject(No.SZXK023)Shenzhen“SanMing”Project of Medicine(No.SZSM201612092)+3 种基金Shenzhen Research and Development Projects(No.JCYJ20170307111755218)Guangdong Basic and Applied Basic Research Foundation(No.2019A1515011290)National Key Research and Development Program of China(No.2016YFC1102103)China Postdoctoral Science Foundation(No.2020M672756)
文摘Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration,blood vessels invasion and transport of nutrient and waste.However,efforts and understanding of the interconnectivity of porous Mg is limited due to the diverse architectures of pore struts and pore size distribution of Mg scaffold systems.In this work,biomimetic hierarchical porous Mg scaffolds with tailored interconnectivity as well as pore size distribution were prepared by template replication of infiltration casting.Mg scaffold with better interconnectivity showed lower mechanical strength.Enlarging interconnected pores would enhance the interconnectivity of the whole scaffold and reduce the change of ion concentration,pH value and osmolality of the degradation microenvironment due to the lower specific surface area.Nevertheless,the degradation rates of five tested Mg scaffolds were no different because of the same geometry of strut unit.Direct cell culture and evaluation of cell density at both sides of four typical Mg scaffolds indicated that cell migration through hierarchical porous Mg scaffolds could be enhanced by not only bigger interconnected pore size but also larger main pore size.In summary,design of interconnectivity in terms of pore size distribution could regulate mechanical strength,microenvironment in cell culture condition and cell migration potential,and beyond that it shows great potential for personalized therapy which could facilitate the regeneration process.
基金supported by Isfahan University of Technology and Ministry of Sciences, Research & Technology in Iran and Materials Science & Engineering School of Nanyang Technological University in Singapore
文摘In this paper, preparation of nano-biphasic calcium phosphate （nBCP）, mechanical behavior and load-bearing of poly （lactide-co-glycolide） （PLGA） and PLGA/nBCP are presented. The nBCP with composition of 63/37 （w/w） HA/-TCP （hydroxyapatite/fl-tricalcium phosphate） was produced by heating of bovine bone at 700℃. Composite scaffolds were made by using PLGA matrix and 10-50 wt% nBCP powders as reinforcement material. All scaffolds were prepared by thermally induced solid-liquid phase separation （TIPS） at -60~C under 4 Pa （0.04 mbar） vacuum. The results of elastic modulus testing were adjusted with Ishai-Cohen and Narkis models for rigid polymeric matrix and compared to each other. PLGA/nBCP scaffolds with 30 wt% nBCP showed the highest value of yield strength among the scaffolds. In addition, it was found that by increasing the nBCP in scaffolds to 50 wt%, the modulus of elasticity was highly enhanced. However, the optimum value of yield strength was obtained at 30 wt% nBCP, and the agglomeration of reinforcing particles at higher percentages caused a reduction in yield strength. It is clear that the elastic modulus of matrix has the significant role in elastic modulus of scaffolds, as also the size of the filler particles in the matrix.
基金financial support from Orthopaedic Research UK (P 470)Arthritis Research UK (grant 20299 and Oxford EOTC)
文摘The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor （VDR）, we examined their response to different concentrations of 25-hydroxy vitamin D3 [25（OH）D3] （100 or 500 nmol·L^-1） and 1,25-dihydroxy vitamin D3 [1,25（OH）2D3] （0.1 or 0.5 nmol·L^-1） metabolites in cell cultures. Specifically, CD14＋ monocytes were cultured in charcoal-stripped serum in the presence of receptor activator of nuclear factor kappa-B ligand （RANKL） and macrophage colony-stimulating factor （M-CSF）. Tartrate-resistant acid phosphatase （TRAP） histochemical staining assays and dentine resorption analysis were used to identify the size and number of osteoclast cells, number of nuclei per cell and resorption activity. The expression of VDR was detected in human bone tissue （ex vivo） by immunohistochemistry and in vitro cell cultures by western blotting. Quantitative reverse transcription-PCR （qRT-PCR） was used to determine the level of expression of vitamin D-related genes in response to vitamin D metabolites. VDR-related genes during osteoclastogenesis, shown by qRT-PCR, was stimulated in response to 500 nmol·L^-1 of 25（OH）D3 and 0.1-0.5 nmol·L^-1 of 1,25（OH）2D3, upregulating cytochrome P450 family 27 subfamily B member I （CYP27B1） and cytochrome P450 family 24 subfamily A member I （CYP24A1）. Osteoclast fusion transcripts transmembrane 7 subfamily member 4 （tm7sf4） and nuclear factor of activated T-cell cytoplasmic 1 （nfatcl） where downregulated in response to vitamin D metabolites. Osteoclast number and resorption activity were also increased. Both 25（OH）D3 and 1,25（OH）2D3 reduced osteoclast size and number when co-treated with RANKL and M-CSF. The evidence for VDR expression in resorbing osteoclasts in vivo and low-dose effects of 1,25（OH）2D3 on osteoclasts in vitro may therefore provide insight into the effects of clinical vitamin D treatments, further providing a counterpoint to the high-dose effects reported from in vitro experiments.
基金financially supported by the National Natural Science Foundation of China(No.82072074)the National Natural Science Foundation of China(No.51801198)+2 种基金funds of Scientific and Technological Plan of Fujian Province(No.2020Y0083)the Natural and Science Foundation of Fujian Province(No.2019I0027)the Funds of Scientific and Technological Plan of Fujian Province(No.2020L3026)。
文摘Lanthanum(La)has tremendous potential in the treatment and prevention of bone diseases especially osteoporosis and metabolic disorders.However,controlling its distribution and keeping the release of La^(3+)ions sustained and steady in the body is still a big challenge.In this study,we prepared La-OCP powders via co-precipitation method,and further prepared La-OCP/PLA porous scaffolds by 3 D printing.La^(3+)was successfully introduced into the OCP crystal structure and substituted Ca^(2+)at the Ca-5 and Ca-8 sites.In particular,some La^(3+)ions were deposited on the crystal surface in the form of nanoparticles.Both octacalcium phosphate(OCP,Ca_(8)H_(2)(PO_(4))_6·5 H_(2)O)crystals and nanoparticles played as the carriers for La^(3+)ions.The La-OCP/PLA scaffolds displayed obvious mineralization effects and sustained release of La^(3+).The scaffolds contained a uniform structure with rough micro surface topography which acted as a suitable pathway for BMSCs cells to adhere,grow and proliferation.At a certain La^(3+)concentration,the extracts from La-OCP/PLA scaffolds increased the expression of osteogenesis-related genes,thus promoting the osteogenic differentiation of BMSCs.Moreover,the extracts regulated the immune responses.The experiment in vivo proved that La-OCP/PLA porous scaffolds were safe and could enhance bone defect regeneration in vivo.These findings suggest that 3 D printed La-OCP/PLA porous scaffolds have promising potentials in bone tissue engineering.
基金This research was funded by Jiangsu Province’s Key Project of Science and Technology(Grant No.BE2018644)Changzhou Health Commission’s Young Talents Science and Technology project(Grant No.QN202029).
文摘Bone tissue engineering(BTE)has proven to be a promising strategy for bone defect repair.Due to its excellent biological properties,gelatin methacrylate(GelMA)hydrogels have been used as bioinks for 3D bioprinting in some BTE studies to produce scaffolds for bone regeneration.However,applications for load-bearing defects are limited by poor mechanical properties and a lack of bioactivity.In this study,3D printing technology was used to create nano-attapulgite(nano-ATP)/GelMA composite hydrogels loaded into mouse bone mesenchymal stem cells(BMSCs)and mouse umbilical vein endothelial cells(MUVECs).The bioprintability,physicochemical properties,and mechanical properties were all thoroughly evaluated.Our findings showed that nano-ATP groups outperform the control group in terms of printability,indicating that nano-ATP is beneficial for printability.Additionally,after incorporation with nano-ATP,the mechanical strength of the composite hydrogels was significantly improved,resulting in adequate mechanical properties for bone regeneration.The presence of nano-ATP in the scaffolds has also been stud-ied for cell-material interactions.The findings show that cells within the scaffold not only have high viability but also a clear proclivity to promote osteogenic differentiation of BMSCs.Besides,the MUVECs-loaded composite hydrogels demonstrated increased angiogenic activity.A cranial defect model was also developed to evaluate the bone repair capability of scaffolds loaded with rat BMSCs.According to histo-logical analysis,cell-laden nano-ATP composite hydrogels can effectively im prove bone regeneration and promote angiogenesis.This study demonstrated the potential of nano-ATP for bone tissue engineering,which should also increase the clinical practicality of nano-ATP.
基金Supported by the National Key Research and Development Program of China,No.2023YFC2508806Key Research and Development Project in Henan Province,No.231111310500+4 种基金Young Elite Scientists Sponsorship Program by CAST,No.2021-QNRC2-A06Scientific Research Project of Henan Zhongyuan Medical Science and Technology Innovation and Development Foundation,No.ZYYC2023ZDYouth Science Award Project of the Provincial-Level Joint Fund for Science and Technology Research and Development Project in Henan Province,No.225200810084Special Project on Training Top Talents in Traditional Chinese Medicine in Henan Province,No.2022ZYBJ242023 Hunan University of Chinese Medicine Postgraduate Innovation Project,No.2023CX64。
文摘The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.
基金supported by the National Natural Science Foundation of China (Nos. 82071164 and 82271016)Key Research Program of Sichuan Science and Technology Department (No. 2021YFS0052)。
文摘Metal-organic frameworks(MOFs), a class of hybrid materials, consist of organic linkers and bridging metal ions or clusters. Their tunable pore sizes, large surface area, good biocompatibility, structural variability in combination with materials and chemicals, and osteogenic effects provide potential approaches for bone tissue engineering and bone diseases. And there are more and more research on MOFs in the field of osteogenesis in recent years. This review presents an overall summary of the application in the bone tissue engineering and bone diseases of MOFs and their composites, starting with the synthesis of MOFs, which discusses the advantages and disadvantages of different syntheses. Then, the biological functions of MOFs are discussed, which are the basics of MOFs applied in the organism. Importantly,mechanisms and abundant applications of MOFs are detailed in the bone tissue engineering and bone diseases. Finally, some prospects of MOFs are discussed, for instance, exploring whether MOFs can be used to treat other bone diseases.
基金supported by the Science and Technology Commission of Shanghai Municipality(No.15JC1491003),China
文摘Bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction.Autografts and allografts have been used in clinical application for some time,but they have disadvantages.With the inherent drawback in the precision and reproducibility of conventional scaffold fabrication techniques,the results of bone surgery may not be ideal.This is despite the introduction of bone tissue engineering which provides a powerful approach for bone repair.Rapid prototyping technologies have emerged as an alternative and have been widely used in bone tissue engineering,enhancing bone tissue regeneration in terms of mechanical strength,pore geometry,and bioactive factors,and overcoming some of the disadvantages of conventional technologies.This review focuses on the basic principles and characteristics of various fabrication technologies,such as stereolithography,selective laser sintering,and fused deposition modeling,and reviews the application of rapid prototyping techniques to scaffolds for bone tissue engineering.In the near future,the use of scaffolds for bone tissue engineering prepared by rapid prototyping technology might be an effective therapeutic strategy for bone defects.
