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
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
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 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
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
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
In order to obtain larger,clinical-scale and practical-scale bone grafts,we have designed both tailored scaffolds and tailored bio incubator with optimal bio-production characteristics.Using DIC files to Simpleware Sc...In order to obtain larger,clinical-scale and practical-scale bone grafts,we have designed both tailored scaffolds and tailored bio incubator with optimal bio-production characteristics.Using DIC files to Simpleware Scan-IP(Simple-ware-exeter United Kingdom),we have digitally reconstructed segmental additive bone-tissue in order to perform images processing.Both hydroxyapatite and tannin composites have been used in order to get the final bone modules combined for retexturing of segmental bone defect.We have found that sectioning of bone segment deficiency reorganizations into well disk-shaped design permits one to standardize the cell culture and seeding protocol,to get better products.The present study concludes that some techniques with cultured cell in segmental bone grafts in the laboratory can be transferred and clinically used.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
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
Presently, there is a high paucity of bone grafts in the United States and worldwide. Regenerating bone is of prime concern due to the current demand of bone grafts and the increasing number of diseases causing bone l...Presently, there is a high paucity of bone grafts in the United States and worldwide. Regenerating bone is of prime concern due to the current demand of bone grafts and the increasing number of diseases causing bone loss. Autogenous bone is the present gold standard of bone regeneration. However, disadvantages like donor site morbidity and its decreased availability limit its use. Even allografts and synthetic grafting materials have their own limitations. As certain specific stem cells can be directed to differentiate into an osteoblastic lineage in the presence of growth factors(GFs), it makes stem cells the ideal agents for bone regeneration.Furthermore, platelet-rich plasma(PRP), which can be easily isolated from whole blood, is often used for bone regeneration, wound healing and bone defect repair. When stem cells are combined with PRP in the presence of GFs, they are able to promote osteogenesis. This review provides in-depth knowledge regarding the use of stem cells and PRP in vitro, in vivo and their application in clinical studies in the future.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
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
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
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 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.
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In order to obtain larger,clinical-scale and practical-scale bone grafts,we have designed both tailored scaffolds and tailored bio incubator with optimal bio-production characteristics.Using DIC files to Simpleware Scan-IP(Simple-ware-exeter United Kingdom),we have digitally reconstructed segmental additive bone-tissue in order to perform images processing.Both hydroxyapatite and tannin composites have been used in order to get the final bone modules combined for retexturing of segmental bone defect.We have found that sectioning of bone segment deficiency reorganizations into well disk-shaped design permits one to standardize the cell culture and seeding protocol,to get better products.The present study concludes that some techniques with cultured cell in segmental bone grafts in the laboratory can be transferred and clinically used.
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.
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 the National Institute of Arthritis and Musculoskeletal and Skin Diseases,and National Institute of Dental and Craniofacial Research under Award Numbers AR061052,AR066101 and DE023105 to S.Y
文摘Presently, there is a high paucity of bone grafts in the United States and worldwide. Regenerating bone is of prime concern due to the current demand of bone grafts and the increasing number of diseases causing bone loss. Autogenous bone is the present gold standard of bone regeneration. However, disadvantages like donor site morbidity and its decreased availability limit its use. Even allografts and synthetic grafting materials have their own limitations. As certain specific stem cells can be directed to differentiate into an osteoblastic lineage in the presence of growth factors(GFs), it makes stem cells the ideal agents for bone regeneration.Furthermore, platelet-rich plasma(PRP), which can be easily isolated from whole blood, is often used for bone regeneration, wound healing and bone defect repair. When stem cells are combined with PRP in the presence of GFs, they are able to promote osteogenesis. This review provides in-depth knowledge regarding the use of stem cells and PRP in vitro, in vivo and their application in clinical studies in the future.
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.
