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
Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant i...Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant interest in bone tissue engineering(BTE)because of their abundant availability,minimally invasive harvesting procedures,and robust differentiation potential into osteogenic lineages.Unlike bone marrow-derived mesenchymal stem cells,AD-MSCs can be easily obtained in large quantities,making them appealing alternatives for therapeutic applications.This review explores hydrogels containing polymers,such as chitosan,collagen,gelatin,and hyaluronic acid,and their composites,tailored for BTE,and emphasizes the importance of these hydrogels as scaffolds for the delivery of AD-MSCs.Various hydrogel fabrication techniques and biocompatibility assessments are discussed,along with innovative modifications to enhance osteogenesis.This review also briefly outlines AD-MSC isolation methods and advanced embedding techniques for precise cell placement,such as direct encapsulation and three-dimensional bioprinting.We discuss the mechanisms of bone regeneration in the AD-MSC-laden hydrogels,including osteoinduction,vascularization,and extracellular matrix remodeling.We also review the preclinical and clinical applications of AD-MSC-hydrogel systems,emphasizing their success and limitations.In this review,we provide a comprehensive overview of AD-MSC-based hydrogel systems to guide the development of effective therapies for bone regeneration.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
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
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
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
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
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 their incre...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
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
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.
文摘Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant interest in bone tissue engineering(BTE)because of their abundant availability,minimally invasive harvesting procedures,and robust differentiation potential into osteogenic lineages.Unlike bone marrow-derived mesenchymal stem cells,AD-MSCs can be easily obtained in large quantities,making them appealing alternatives for therapeutic applications.This review explores hydrogels containing polymers,such as chitosan,collagen,gelatin,and hyaluronic acid,and their composites,tailored for BTE,and emphasizes the importance of these hydrogels as scaffolds for the delivery of AD-MSCs.Various hydrogel fabrication techniques and biocompatibility assessments are discussed,along with innovative modifications to enhance osteogenesis.This review also briefly outlines AD-MSC isolation methods and advanced embedding techniques for precise cell placement,such as direct encapsulation and three-dimensional bioprinting.We discuss the mechanisms of bone regeneration in the AD-MSC-laden hydrogels,including osteoinduction,vascularization,and extracellular matrix remodeling.We also review the preclinical and clinical applications of AD-MSC-hydrogel systems,emphasizing their success and limitations.In this review,we provide a comprehensive overview of AD-MSC-based hydrogel systems to guide the development of effective therapies for bone regeneration.
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.
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.
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.
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.
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.
