Polycaprolactone(PCL)scaffolds that are produced through additive manufacturing are one of the most researched bone tissue engineering structures in the field.Due to the intrinsic limitations of PCL,carbon nanomateria...Polycaprolactone(PCL)scaffolds that are produced through additive manufacturing are one of the most researched bone tissue engineering structures in the field.Due to the intrinsic limitations of PCL,carbon nanomaterials are often investigated to reinforce the PCL scaffolds.Despite several studies that have been conducted on carbon nanomaterials,such as graphene(G)and graphene oxide(GO),certain challenges remain in terms of the precise design of the biological and nonbiological properties of the scaffolds.This paper addresses this limitation by investigating both the nonbiological(element composition,surface,degradation,and thermal and mechanical properties)and biological characteristics of carbon nanomaterial-reinforced PCL scaffolds for bone tissue engineering applications.Results showed that the incorporation of G and GO increased surface properties(reduced modulus and wettability),material crystallinity,crystallization temperature,and degradation rate.However,the variations in compressive modulus,strength,surface hardness,and cell metabolic activity strongly depended on the type of reinforcement.Finally,a series of phenomenological models were developed based on experimental results to describe the variations of scaffold’s weight,fiber diameter,porosity,and mechanical properties as functions of degradation time and carbon nanomaterial concentrations.The results presented in this paper enable the design of three-dimensional(3D)bone scaffolds with tuned properties by adjusting the type and concentration of different functional fillers.展开更多
Nonunion represents a crucial challenge in orthopedic medicine,demanding innovative solutions beyond the scope of traditional bone grafting methods.Among the various strategies available,magnesium(Mg)implants have bee...Nonunion represents a crucial challenge in orthopedic medicine,demanding innovative solutions beyond the scope of traditional bone grafting methods.Among the various strategies available,magnesium(Mg)implants have been recognized for their biocompatibility and biodegradability.However,their susceptibility to rapid corrosion and degradation has garnered notable research interest in bone tissue engineering(BTE),particularly in the development of Mg-incorporated biocomposite scaffolds.These scaffolds gradually release Mg2+,which enhances immunomodulation,osteogenesis,and angiogenesis,thus facilitating effective bone regeneration.This review presents myriad fabrication techniques used to create Mg-incorporated biocomposite scaffolds,including electrospinning,three-dimensional printing,and sol-gel synthesis.Despite these advancements,the application of Mg-incorporated biocomposite scaffolds faces challenges such as controlling the degradation rate of Mg and ensuring mechanical stability.These limitations highlight the necessity for ongoing research aimed at refining fabrication techniques to better regulate the physicochemical and osteogenic properties of scaffolds.This review provides insights into the potential of Mg-incorporated biocomposite scaffolds for BTE and the challenges that need to be addressed for their successful translation into clinical applications.展开更多
Bone is a complex but orderly mineralized tissue with hydroxyapatite(HA)as the inorganic phase and collagen as the organic phase.Inspired by natural bone tissues,HA-mineralized hydrogels have been widely designed and ...Bone is a complex but orderly mineralized tissue with hydroxyapatite(HA)as the inorganic phase and collagen as the organic phase.Inspired by natural bone tissues,HA-mineralized hydrogels have been widely designed and used in bone tissue engineering.HA is majorly utilized for the treatment of bone defects because of its excellent osteoconduction and bone inductivity.Hydrogel is a three-dimensional hydrophilic network structure with similar properties to the extracellular matrix(ECM).The combination of HA and hydrogels produces a new hybrid material that could effectively promote osteointegration and accelerate the healing of bone defects.In this review,the structure and growth of bone and the common strategies used to prepare HA were briefly introduced.Importantly,we discussed the fabrication of HA mineralized hydrogels from simple blending to in situ mineralization.We hope this review can provide a reference for the development of bone repair hydrogels.展开更多
Three-dimensional honeycomb-structured magnesium (Mg) scaffolds with interconnected pores of accurately controlled pore size and porosity were fabricated by laser perforation technique. Biodegradable and bioactiveβ...Three-dimensional honeycomb-structured magnesium (Mg) scaffolds with interconnected pores of accurately controlled pore size and porosity were fabricated by laser perforation technique. Biodegradable and bioactiveβ- tricalcium phosphate (β-TCP) coatings were prepared on and the biodegradation mechanism was simply evaluated the porous Mg to further improve its biocompatibility, in vitro. It was found that the mechanical properties of this type of porous Mg significantly depended on its porosity. Elastic modulus and compressive strength similar to human bones could be obtained for the porous Mg with porosity of 42.6%-51%. It was observed that the human osteosarcoma cells (UMR106) were well adhered and proliferated on the surface of the β- TCP coated porous Mg, which indicates that theβ-TCP coated porous Mg is promising to be a bone tissue engineering scaffold material.展开更多
A new biomimetic bone tissue engineering scaffold material, nano-HAI PLGA-( PEG-Asp )n composite, was synthesized by a biologically inspired self-assembling approach. A novel biodegradable PLGA- ( PEG-Asp )n cop...A new biomimetic bone tissue engineering scaffold material, nano-HAI PLGA-( PEG-Asp )n composite, was synthesized by a biologically inspired self-assembling approach. A novel biodegradable PLGA- ( PEG-Asp )n copolymer with pendant amine functional groups and enhanced hydrophilicity woo synthesized by bulk ring-opening copolymerization by DL-lactide( DLLA) and glycolide( GA ) with Aspartic acid ( Asp )-Polyethylene glycol(PEG) alt-prepolymer. A Three-dimensional, porous scaffold of the PLGA-( PEG- Asp)n copolymer was fabricated by a solvent casting , particulate leaching process. The scaffold woo then incubated in modified simulated body fluid (naSBF). Growth of HA nanocrystals on the inner pore surfaces of the porous scaffold is confirmed by calcium ion binding analyses, SEM , mass increooe meoourements and quantification of phosphate content within scaffolds. SEM analysis demonstrated the nucleation and growth of a continuous bonelike, low crystalline carbonated HA nanocrystals on the inner pore surfaces of the PLGA- ( PEG-Asp )n scaffolds. The amount of calcium binding, total mass and the mass of phosphate on experimental PLGA- ( PEG-Asp ) n scaffolds at different incubation times in mSBF was significantly greater than that of control PLGA scaffolds. This nano-HA/ PLGA-( PEG- Asp )n composite stunts some features of natural bone both in main composition and hierarchical microstrueture. The Asp- PEG alt-prepolymer modified PleA copolymer provide a controllable high surface density and distribution of anionic functional groups which would enhance nucleation and growth of bonelike mineral following exposure to mSBF. This biomimetic treatment provides a simple method for surface functionalization and sabsequent mineral nucleation and self-oosembling on bodegradable polymer scaffolds for tissue engineering.展开更多
The biocompatibility and osteogenic activity of allogenic decalcified bone matrix (DBM) used as a carrier for bone tissue engineering were studied. Following the method described by Urist, allogenic DBM was made. In v...The biocompatibility and osteogenic activity of allogenic decalcified bone matrix (DBM) used as a carrier for bone tissue engineering were studied. Following the method described by Urist, allogenic DBM was made. In vitro, DBM and bone marrow stromal cell (BMSC) from rabbits were co-cultured for 3-7 days and subjected to HE staining, and a series of histomorphological observations were performed under phase-contrast microscopy and scanning electron microscopy (SEM). In vivo the mixture of DBM/BMSC co-cultured for 3 days was planted into one side of muscules sacrospinalis of rabbits, and the DBM without BMSC was planted into other side as control. Specimens were collected at postoperative week 1, 2 and 4, and subjected to HE staining, and observed under SEM. The results showed during culture in vitro, the BMSCs adherent to the wall of DBM grew, proliferated and had secretive activity. The in vivo experiment revealed that BMSCs and undifferentiated mesenchymal cells in the perivascular region invaded gradually and proliferated together in DBM/BMSC group, and colony-forming units of chondrocytes were found. Osteoblasts, trabecular bone and medullary cavity appeared. The inflammatory reaction around muscles almost disappeared at the second weeks. In pure DBM group, the similar changes appeared from the surface of the DBM to center, and the volume of total regenerate bones was less than the DBM/BMSC group at the same time. The results indicated that the mixture of DBM and BMSC had good biocompatibility and ectopic induced osteogenic activity.展开更多
Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate (CAP) biomaterials/scaffolds are of special interest as they share chemical/crystallographic simila...Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate (CAP) biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review: nanostructured calcium phosphate cement (CPC); nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/ morphology, differentiation and in vivo bone regeneration. Several trends can be seen: (i) nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; (ii) the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; (iii) nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; (iv) combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and (v) cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.展开更多
Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration,blood vessels invasion and transport of nutrient and waste.However,efforts and understanding of the interconnec...Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration,blood vessels invasion and transport of nutrient and waste.However,efforts and understanding of the interconnectivity of porous Mg is limited due to the diverse architectures of pore struts and pore size distribution of Mg scaffold systems.In this work,biomimetic hierarchical porous Mg scaffolds with tailored interconnectivity as well as pore size distribution were prepared by template replication of infiltration casting.Mg scaffold with better interconnectivity showed lower mechanical strength.Enlarging interconnected pores would enhance the interconnectivity of the whole scaffold and reduce the change of ion concentration,pH value and osmolality of the degradation microenvironment due to the lower specific surface area.Nevertheless,the degradation rates of five tested Mg scaffolds were no different because of the same geometry of strut unit.Direct cell culture and evaluation of cell density at both sides of four typical Mg scaffolds indicated that cell migration through hierarchical porous Mg scaffolds could be enhanced by not only bigger interconnected pore size but also larger main pore size.In summary,design of interconnectivity in terms of pore size distribution could regulate mechanical strength,microenvironment in cell culture condition and cell migration potential,and beyond that it shows great potential for personalized therapy which could facilitate the regeneration process.展开更多
The optimization of the scaffolds to provide a suitable matrix and accelerate the regeneration process is vital for bone tissue engineering.However,poor mechanical and biological characteristics remain the primary cha...The optimization of the scaffolds to provide a suitable matrix and accelerate the regeneration process is vital for bone tissue engineering.However,poor mechanical and biological characteristics remain the primary challenges that must be addressed.For example,although bredigite(Br)has shown great potential for application in bone tissue engineering,it easily fails in replacement.In the present work,these challenges are addressed by reinforcing the Br matrix with nanosheets of graphene oxide(rGO)that have been reduced by bovine serum albumin(BSA)in order to enhance the mechanical properties and biological behavior.The reduction of graphene oxide by BSA improves the water stability of the nanosheets and provides an electrostatic interaction between theBSA-rGO nanosheets and theBr particles.The high thermal conductivity of theBSA-rGO nanosheets decreases the porosity of the Br by transferring heat to the core of the tablet.Furthermore,the addition of BSA-rGO nanosheets into the Br matrix enhances the adhesion of G-292 cells on the surface of the tablets.These findings suggest that the tablet consisting of BSA-rGO-reinforced Br has encouraging potential for application in bone tissue engineering.展开更多
Colloidal gels made of oppositely charged nanoparticles are a novel class of hydrogels and can exhibit pseudoplastic behavior which will enable them to mold easily into specific shapes.These moldable gels can be used ...Colloidal gels made of oppositely charged nanoparticles are a novel class of hydrogels and can exhibit pseudoplastic behavior which will enable them to mold easily into specific shapes.These moldable gels can be used as building blocks to self-assemble into integral scaffolds from bottom to up through electrostatic forces.However,they are too weak to maintain scaffold morphology just depending on interparticle interactions such as Van der Waals attraction and electrostatic forces especially for bone tissue engineering.In this study,oppositely charged gelatin nanoparticles were firstly prepared by two-step desolvation method,followed by the mixture with water to form colloid gels.To solve the problem of weak mechanical performance of colloid gels, gelatin macromolecules were introduced into the prepared gels to form blend gels.The blend gels can be easily processed into three-dimensional( 3D) porous scaffolds via motor assisted microsyringe( MAM)system,a nozzle-based rapid prototyping technology,under mild conditions.After fabrication the scaffolds were crosslinked by glutaraldehyde( GA,25% solution in water by weight),then the crosslinked gelatin macromolecules network could form to improve the mechanical properties of colloid gels.The average particle size and zeta potential of gelatin nanoparticles were measured by NanoZS instrument.The morphology and microstructures of scaffolds were characterized by macroscopic images.The mechanical properties of the scaffolds were studied by a universal material testing machine.展开更多
BACKGROUND Bone tissue engineering is an area of continued interest within orthopaedic surgery,as it promises to create implantable bone substitute materials that obviate the need for autologous bone graft.Recently,ox...BACKGROUND Bone tissue engineering is an area of continued interest within orthopaedic surgery,as it promises to create implantable bone substitute materials that obviate the need for autologous bone graft.Recently,oxysterols–oxygenated derivatives of cholesterol-have been proposed as a novel class of osteoinductive small molecules for bone tissue engineering.Here,we present the first systematic review of the in vivo evidence describing the potential therapeutic utility of oxysterols for bone tissue engineering.AIM To systematically review the available literature examining the effect of oxysterols on in vivo bone formation.METHODS We conducted a systematic review of the literature following PRISMA guidelines.Using the PubMed/MEDLINE,Embase,and Web of Science databases,we queried all publications in the English-language literature investigating the effect of oxysterols on in vivo bone formation.Articles were screened for eligibility using PICOS criteria and assessed for potential bias using an expanded version of the SYRCLE Risk of Bias assessment tool.All full-text articles examining the effect of oxysterols on in vivo bone formation were included.Extracted data included:Animal species,surgical/defect model,description of therapeutic and control treatments,and method for assessing bone growth.Primary outcome was fusion rate for spinal fusion models and percent bone regeneration for critical-sized defect models.Data were tabulated and described by both surgical/defect model and oxysterol employed.Additionally,data from all included studies were aggregated to posit the mechanism by which oxysterols may mediate in vivo bone formation.RESULTS Our search identified 267 unique articles,of which 27 underwent full-text review.Thirteen studies(all preclinical)met our inclusion/exclusion criteria.Of the 13 included studies,5 employed spinal fusion models,2 employed critical-sized alveolar defect models,and 6 employed critical-sized calvarial defect models.Based upon SYRCLE criteria,the included studies were found to possess an overall“unclear risk of bias”;54%of studies reported treatment randomization and 38%reported blinding at any level.Overall,seven unique oxysterols were evaluated:20(S)-hydroxycholesterol,22(R)-hydroxycholesterol,22(S)-hydroxycholesterol,Oxy4/Oxy34,Oxy18,Oxy21/Oxy133,and Oxy49.All had statistically significant in vivo osteoinductive properties,with Oxy4/Oxy34,Oxy21/Oxy133,and Oxy49 showing a dose-dependent effect in some cases.In the eight studies that directly compared oxysterols to rhBMP-2-treated animals,similar rates of bone growth occurred in the two groups.Biochemical investigation of these effects suggests that they may be primarily mediated by direct activation of Smoothened in the Hedgehog signaling pathway.CONCLUSION Present preclinical evidence suggests oxysterols significantly augment in vivo bone formation.However,clinical trials are necessary to determine which have the greatest therapeutic potential for orthopaedic surgery patients.展开更多
Tissue engineering’s main goal is to regenerate or replace tissues or organs that have been destroyed by disease,injury,or congenital disabilities.Tissue engineering now uses artificial supporting structures called s...Tissue engineering’s main goal is to regenerate or replace tissues or organs that have been destroyed by disease,injury,or congenital disabilities.Tissue engineering now uses artificial supporting structures called scaffolds to restore damaged tissues and organs.These are utilized to attach the right cells and then grow them.Rapid prototyping appears to be the most promising technology due to its high level of precision and control.Bone tissue replacement“scaffolding”is a common theme discussed in this article.The fused deposition technique was used to construct our scaffold,and a polymer called polylactic acids and soybean oil resin were used to construct our samples.The samples were then divided into two groups;the first group was left without immersion in the simulated body fluid and served as a control for comparison.The second group was immersed in the simulated body fluid.The results of the Field Emission Scanning Electron Microscope(FESEM),Energy Dispersive X-ray Spectroscopy(EDX)and X-ray diffraction(XRD)were utilized to interpret the surface attachment to ions,elements,and compounds,giving us a new perspective on scaffold architecture.In this study,an innovative method has been used to print therapeutic scaffold that combines fused deposition three-dimensional printing with ultraviolet curing to create a high-quality biodegradable polymeric scaffold.Finally,the results demonstrate that adding soybean oil resin to the PLA increased ion attachment to the surface while also attracting tricalcium phosphate formation on the surface of the scaffold,which is highly promising in bone tissue replacement.In conclusion,the soybean oil resin,which is new in the field of bone tissue engineering,shows magnificent characteristics and is a good replacement biopolymer that replaces many ceramic and polymeric materials used in this field that have poor morphological characteristics.展开更多
A novel method of designing and preparing bone tissue engineering scaffolds with controllable porous structure of both macro channels and micro pores was proposed. The CAD software UG NX3.0 was used to design the macr...A novel method of designing and preparing bone tissue engineering scaffolds with controllable porous structure of both macro channels and micro pores was proposed. The CAD software UG NX3.0 was used to design the macro channels' shape, size and distribution. By integrating rapid prototyping and traditional porogen technique, the macro channels and micro pores were formed respectively. The size, shape and quantity of micro pores were controlled by porogen particulates. The sintered β-TCP porous scaffolds possessed connective macro channels of approximately 500 μm and micro pores of 200-400 μm. The porosity and connectivity of micro pores became higher with the increase of porogen ratio, while the mechanical properties weakened. The average porosity and compressive strength offl-TCP scaffolds prepared with porogen ratio of 60wt% were 78.12% and 0.2983 MPa, respectively. The cells' adhesion ratio of scaffolds was 67.43%. The ALP activity, OCN content and cells micro morphology indicated that cells grew and proliferated well on the scaffolds.展开更多
The limited bioactivity of scaffold materials is an important factor that restricts the development of bone tissue engineering.Wnt3a activates the classicWnt/β-catenin signaling pathway which effects bone growth and ...The limited bioactivity of scaffold materials is an important factor that restricts the development of bone tissue engineering.Wnt3a activates the classicWnt/β-catenin signaling pathway which effects bone growth and development by the accumulation ofβ-catenin in the nucleus.In this study,we fabricated 3D printed PCL scaffold with Wnt3a-induced murine bone marrow-derived stromal cell line ST2 decellularized matrix(Wnt3a-ST2-dCM-PCL)and ST2 decellularized matrix(ST2-dCM-PCL)by freeze-thaw cycle and DNase decellularization treatment which efficiently decellularized>90%DNA while preserved most protein.Compared to ST2-dCM-PCL,Wnt3a-ST2-dCM-PCL significantly enhanced newly-seeded ST2 proliferation,osteogenic differentiation and upregulated osteogenic marker genes alkaline phosphatase(Alp),Runx2,type I collagen(Col 1)and osteocalcin(Ocn)mRNA expression.After 14 days of osteogenic induction,Wnt3a-ST2-dCM-PCL promoted ST2 mineralization.These results demonstrated that Wnt3a-induced ST2 decellularized matrix improve scaffold materials’osteoinductivity and osteoconductivity.展开更多
The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/...The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/PCL)composite scaffold with porous structure was fabricated by thermally induced phase separation(TIPS).Dexamethasone(DEX)was incorporated into PLGA microspheres and then loaded on the PLLA/PLGA/PCL scaffoldtopreparethedesiredcompositescaffold.The physicochemical properties of the prepared composite scaffold were characterized.The morphology of rat bone marrow mesenchymal stem cells(BMSCs)grown on scaffolds was observed using scanning electron microscope(SEM)and fluorescence microscope.The resultsshowedthatthePLLA/PLGA/PCLscaffoldhad interconnected macropores and biomimetic nanofibrous structure.In addition,DEX can be released from scaffold in a sustained manner.More importantly,DEX loaded composite scaffold can effectively support the proliferation of BMSCs as indicated by fluorescence observation and cell proliferation assay.The results suggested that the prepared PLLA/PLGA/PCL composite scaffold incorporating drug-loaded PLGA microspheres could hold great potential for bone tissue engineering applications.展开更多
The customized implants which are composed of polycaprolactone( PCL) and strontium substituted nanohydroxyapatite( SrHA) were fabricated successfully by using fused deposition modeling( FDM),which is a simple 3 D prin...The customized implants which are composed of polycaprolactone( PCL) and strontium substituted nanohydroxyapatite( SrHA) were fabricated successfully by using fused deposition modeling( FDM),which is a simple 3 D printing technology for fabricating personalized products. The physical and chemical properties of composite scaffolds were characterized by transmission electron microscopy( TEM), Fourier transform infrared spectroscopy( FTIR), X-Ray diffraction( XRD) and inductively coupled plasma-atomic emission spectroscopy( ICPAES). The results suggested that strontium element was successfully doped into nanohydroxyapatite and all scaffolds showed the homogeneous network structure. Furthermore, the in vitro biocompatibility of the scaffolds was evaluated by cell counting kit-8( CCK-8) assay. The data indicated that the prepared scaffolds exhibited excellent biocompatibility to bone marrow mesenchymal stem cells( BMSCs). Besides,strontium element can be released from PCL-SrHA scaffolds in a sustained manner. Therefore,the 3 D printing PCL-SrHA scaffolds hold great potential for bone tissue engineering.展开更多
Effective bone regeneration through tissue engineering requires a combination of osteogenic progenitors,osteoinductive biofactors and biocompatible scaffold materials.Mesenchymal stem cells(MSCs)represent the most pro...Effective bone regeneration through tissue engineering requires a combination of osteogenic progenitors,osteoinductive biofactors and biocompatible scaffold materials.Mesenchymal stem cells(MSCs)represent the most promising seed cells for bone tissue engineering.As multipotent stem cells that can self-renew and differentiate into multiple lineages including bone and fat,MSCs can be isolated from numerous tissues and exhibit varied differentiation potential.To identify an optimal progenitor cell source for bone tissue engineering,we analyzed the proliferative activity and osteogenic potential of four commonly-used mouse MSC sources,including immortalized mouse embryonic fibroblasts(iMEF),immortalized mouse bone marrow stromal stem cells(imBMSC),immortalized mouse calvarial mesenchymal progenitors(iCAL),and immortalized mouse adipose-derived mesenchymal stem cells(iMAD).We found that iMAD exhibited highest osteogenic and adipogenic capabilities upon BMP9 stimulation in vitro,whereas iMAD and iCAL exhibited highest osteogenic capability in BMP9-induced ectopic osteogenesis and critical-sized calvarial defect repair.Transcriptomic analysis revealed that,while each MSC line regulated a distinct set of target genes upon BMP9 stimulation,all MSC lines underwent osteogenic differentiation by regulating osteogenesis-related signaling including Wnt,TGF-β,PI3K/AKT,MAPK,Hippo and JAK-STAT pathways.Collectively,our results demonstrate that adipose-derived MSCs represent optimal progenitor sources for cell-based bone tissue engineering.展开更多
Bone fractures are common occurrence in clinical settings,creating a high demand for effective repair material.Unfortunately,limited graft availability,donor site morbidities,unpredictable clinical outcomes,immunologi...Bone fractures are common occurrence in clinical settings,creating a high demand for effective repair material.Unfortunately,limited graft availability,donor site morbidities,unpredictable clinical outcomes,immunologic reactions,infection risks,and geometrical mismatching concerns hampered tissue graft use and underscored the need for scaffolds for more effective bone reconstructions due to their tunable properties.Significant progress has been carried out in past decade in the fields of nanoceramics synthesis,bioconjugate chemistry,and composite material processing.This review outlines hierarchical structures and biology of bone tissue,materialistic compo-nents of scaffolds(bioceramics,polymers,bioactive drugs),featured scaffolding strategies(nanofibers,hydrogels,aerogels,bioprinting,and fiber-reinforced composite),and emphasis that hierarchical and physiochemical char-acteristics of bone should be used as an inspiration for scaffold design.This review discussed how differences in materiobiological aspects of scaffolds,such as polymer/bioceramic nanocomposite,mineralized nanocomposite,matrix-rich nanocomposite,3D microenvironmental cues,pore space cues,mechanical cues,usage of physical stimulation(magnetic,electroactive,and photoactivated cues),surface cues(wettability,roughness,textured,and surface charge),and biointerface cues(cell-biomaterial interactions,cell-selective homing,and cell regula-tory strategies)modulate cellular and biological response for bone tissue engineering.This study further outlines the challenges and benefits of integrating materiobiological cues of scaffolds for bone tissue engineering.展开更多
In the field of bone defect repair,critical requirements for favorable cytocompatibility and optimal mechanical properties have propelled research efforts towards the development of composite materials.In this study,c...In the field of bone defect repair,critical requirements for favorable cytocompatibility and optimal mechanical properties have propelled research efforts towards the development of composite materials.In this study,carbon nanotubes/polylactic acid/hydroxyapatite(CNTs/PLA/HA)scaffolds with different contents(0.5,1,1.5 and 2 wt.%)of CNTs were prepared by the thermally induced phase separation(TIPS)method.The results revealed that the composite scaffolds had uniform pores with high porosities over 68%and high through performances.The addition of CNTs significantly enhanced the mechanical properties of resulted PLA/HA,in which the 1.5 wt.%CNTs/PLA/HA composite scaffold demonstrated the optimum mechanical behaviors with the bending elastic modulus of(868.5±12.34)MPa,the tensile elastic modulus of(209.51±12.73)MPa,and the tensile strength of(3.26±0.61)MPa.Furthermore,L929 cells on the 1.5 wt.%CNTs/PLA/HA scaffold displayed good spreading performance and favorable cytocompatibility.Therefore,it is expected that the 1.5 wt.%CNTs/PLA/HA scaffold has potential applications in bone tissue engineering.展开更多
基金The authors wish to acknowledge Engineering and Physical Sciences Research Council(EPSRC)UK for the Global Challenges Research Fund(No.EP/R015139/1)Rosetrees Trust UK&Stoneygate Trust UK for the Enterprise Fellowship(Ref:M874).
文摘Polycaprolactone(PCL)scaffolds that are produced through additive manufacturing are one of the most researched bone tissue engineering structures in the field.Due to the intrinsic limitations of PCL,carbon nanomaterials are often investigated to reinforce the PCL scaffolds.Despite several studies that have been conducted on carbon nanomaterials,such as graphene(G)and graphene oxide(GO),certain challenges remain in terms of the precise design of the biological and nonbiological properties of the scaffolds.This paper addresses this limitation by investigating both the nonbiological(element composition,surface,degradation,and thermal and mechanical properties)and biological characteristics of carbon nanomaterial-reinforced PCL scaffolds for bone tissue engineering applications.Results showed that the incorporation of G and GO increased surface properties(reduced modulus and wettability),material crystallinity,crystallization temperature,and degradation rate.However,the variations in compressive modulus,strength,surface hardness,and cell metabolic activity strongly depended on the type of reinforcement.Finally,a series of phenomenological models were developed based on experimental results to describe the variations of scaffold’s weight,fiber diameter,porosity,and mechanical properties as functions of degradation time and carbon nanomaterial concentrations.The results presented in this paper enable the design of three-dimensional(3D)bone scaffolds with tuned properties by adjusting the type and concentration of different functional fillers.
文摘Nonunion represents a crucial challenge in orthopedic medicine,demanding innovative solutions beyond the scope of traditional bone grafting methods.Among the various strategies available,magnesium(Mg)implants have been recognized for their biocompatibility and biodegradability.However,their susceptibility to rapid corrosion and degradation has garnered notable research interest in bone tissue engineering(BTE),particularly in the development of Mg-incorporated biocomposite scaffolds.These scaffolds gradually release Mg2+,which enhances immunomodulation,osteogenesis,and angiogenesis,thus facilitating effective bone regeneration.This review presents myriad fabrication techniques used to create Mg-incorporated biocomposite scaffolds,including electrospinning,three-dimensional printing,and sol-gel synthesis.Despite these advancements,the application of Mg-incorporated biocomposite scaffolds faces challenges such as controlling the degradation rate of Mg and ensuring mechanical stability.These limitations highlight the necessity for ongoing research aimed at refining fabrication techniques to better regulate the physicochemical and osteogenic properties of scaffolds.This review provides insights into the potential of Mg-incorporated biocomposite scaffolds for BTE and the challenges that need to be addressed for their successful translation into clinical applications.
基金supported by the National Natural Science Foundation of China(Grant no:12272253)Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(Grant no:2021SX-AT008,2021SX-AT009).
文摘Bone is a complex but orderly mineralized tissue with hydroxyapatite(HA)as the inorganic phase and collagen as the organic phase.Inspired by natural bone tissues,HA-mineralized hydrogels have been widely designed and used in bone tissue engineering.HA is majorly utilized for the treatment of bone defects because of its excellent osteoconduction and bone inductivity.Hydrogel is a three-dimensional hydrophilic network structure with similar properties to the extracellular matrix(ECM).The combination of HA and hydrogels produces a new hybrid material that could effectively promote osteointegration and accelerate the healing of bone defects.In this review,the structure and growth of bone and the common strategies used to prepare HA were briefly introduced.Importantly,we discussed the fabrication of HA mineralized hydrogels from simple blending to in situ mineralization.We hope this review can provide a reference for the development of bone repair hydrogels.
基金supported by Chinese Academy of Sciences (The Applied Research of Bioactive Bone Implantation Materials, No. KGCX2-YW-207)
文摘Three-dimensional honeycomb-structured magnesium (Mg) scaffolds with interconnected pores of accurately controlled pore size and porosity were fabricated by laser perforation technique. Biodegradable and bioactiveβ- tricalcium phosphate (β-TCP) coatings were prepared on and the biodegradation mechanism was simply evaluated the porous Mg to further improve its biocompatibility, in vitro. It was found that the mechanical properties of this type of porous Mg significantly depended on its porosity. Elastic modulus and compressive strength similar to human bones could be obtained for the porous Mg with porosity of 42.6%-51%. It was observed that the human osteosarcoma cells (UMR106) were well adhered and proliferated on the surface of the β- TCP coated porous Mg, which indicates that theβ-TCP coated porous Mg is promising to be a bone tissue engineering scaffold material.
文摘A new biomimetic bone tissue engineering scaffold material, nano-HAI PLGA-( PEG-Asp )n composite, was synthesized by a biologically inspired self-assembling approach. A novel biodegradable PLGA- ( PEG-Asp )n copolymer with pendant amine functional groups and enhanced hydrophilicity woo synthesized by bulk ring-opening copolymerization by DL-lactide( DLLA) and glycolide( GA ) with Aspartic acid ( Asp )-Polyethylene glycol(PEG) alt-prepolymer. A Three-dimensional, porous scaffold of the PLGA-( PEG- Asp)n copolymer was fabricated by a solvent casting , particulate leaching process. The scaffold woo then incubated in modified simulated body fluid (naSBF). Growth of HA nanocrystals on the inner pore surfaces of the porous scaffold is confirmed by calcium ion binding analyses, SEM , mass increooe meoourements and quantification of phosphate content within scaffolds. SEM analysis demonstrated the nucleation and growth of a continuous bonelike, low crystalline carbonated HA nanocrystals on the inner pore surfaces of the PLGA- ( PEG-Asp )n scaffolds. The amount of calcium binding, total mass and the mass of phosphate on experimental PLGA- ( PEG-Asp ) n scaffolds at different incubation times in mSBF was significantly greater than that of control PLGA scaffolds. This nano-HA/ PLGA-( PEG- Asp )n composite stunts some features of natural bone both in main composition and hierarchical microstrueture. The Asp- PEG alt-prepolymer modified PleA copolymer provide a controllable high surface density and distribution of anionic functional groups which would enhance nucleation and growth of bonelike mineral following exposure to mSBF. This biomimetic treatment provides a simple method for surface functionalization and sabsequent mineral nucleation and self-oosembling on bodegradable polymer scaffolds for tissue engineering.
文摘The biocompatibility and osteogenic activity of allogenic decalcified bone matrix (DBM) used as a carrier for bone tissue engineering were studied. Following the method described by Urist, allogenic DBM was made. In vitro, DBM and bone marrow stromal cell (BMSC) from rabbits were co-cultured for 3-7 days and subjected to HE staining, and a series of histomorphological observations were performed under phase-contrast microscopy and scanning electron microscopy (SEM). In vivo the mixture of DBM/BMSC co-cultured for 3 days was planted into one side of muscules sacrospinalis of rabbits, and the DBM without BMSC was planted into other side as control. Specimens were collected at postoperative week 1, 2 and 4, and subjected to HE staining, and observed under SEM. The results showed during culture in vitro, the BMSCs adherent to the wall of DBM grew, proliferated and had secretive activity. The in vivo experiment revealed that BMSCs and undifferentiated mesenchymal cells in the perivascular region invaded gradually and proliferated together in DBM/BMSC group, and colony-forming units of chondrocytes were found. Osteoblasts, trabecular bone and medullary cavity appeared. The inflammatory reaction around muscles almost disappeared at the second weeks. In pure DBM group, the similar changes appeared from the surface of the DBM to center, and the volume of total regenerate bones was less than the DBM/BMSC group at the same time. The results indicated that the mixture of DBM and BMSC had good biocompatibility and ectopic induced osteogenic activity.
基金supported by NIH R01 DE14190 and R21 DE22625 (HX)National Science Foundation of China 31100695 and 31328008 (LZ), 81401794 (PW)Maryland Stem Cell Research Fund and University of Maryland School of Dentistry
文摘Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate (CAP) biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review: nanostructured calcium phosphate cement (CPC); nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/ morphology, differentiation and in vivo bone regeneration. Several trends can be seen: (i) nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; (ii) the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; (iii) nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; (iv) combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and (v) cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.
基金supported by grants from Shenzhen Key Medical Subject(No.SZXK023)Shenzhen“SanMing”Project of Medicine(No.SZSM201612092)+3 种基金Shenzhen Research and Development Projects(No.JCYJ20170307111755218)Guangdong Basic and Applied Basic Research Foundation(No.2019A1515011290)National Key Research and Development Program of China(No.2016YFC1102103)China Postdoctoral Science Foundation(No.2020M672756)
文摘Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration,blood vessels invasion and transport of nutrient and waste.However,efforts and understanding of the interconnectivity of porous Mg is limited due to the diverse architectures of pore struts and pore size distribution of Mg scaffold systems.In this work,biomimetic hierarchical porous Mg scaffolds with tailored interconnectivity as well as pore size distribution were prepared by template replication of infiltration casting.Mg scaffold with better interconnectivity showed lower mechanical strength.Enlarging interconnected pores would enhance the interconnectivity of the whole scaffold and reduce the change of ion concentration,pH value and osmolality of the degradation microenvironment due to the lower specific surface area.Nevertheless,the degradation rates of five tested Mg scaffolds were no different because of the same geometry of strut unit.Direct cell culture and evaluation of cell density at both sides of four typical Mg scaffolds indicated that cell migration through hierarchical porous Mg scaffolds could be enhanced by not only bigger interconnected pore size but also larger main pore size.In summary,design of interconnectivity in terms of pore size distribution could regulate mechanical strength,microenvironment in cell culture condition and cell migration potential,and beyond that it shows great potential for personalized therapy which could facilitate the regeneration process.
基金Thiswork is financially supported by IranUniversity of Science and Technology(IUST)and Motamed Cancer Institute(ACECR).
文摘The optimization of the scaffolds to provide a suitable matrix and accelerate the regeneration process is vital for bone tissue engineering.However,poor mechanical and biological characteristics remain the primary challenges that must be addressed.For example,although bredigite(Br)has shown great potential for application in bone tissue engineering,it easily fails in replacement.In the present work,these challenges are addressed by reinforcing the Br matrix with nanosheets of graphene oxide(rGO)that have been reduced by bovine serum albumin(BSA)in order to enhance the mechanical properties and biological behavior.The reduction of graphene oxide by BSA improves the water stability of the nanosheets and provides an electrostatic interaction between theBSA-rGO nanosheets and theBr particles.The high thermal conductivity of theBSA-rGO nanosheets decreases the porosity of the Br by transferring heat to the core of the tablet.Furthermore,the addition of BSA-rGO nanosheets into the Br matrix enhances the adhesion of G-292 cells on the surface of the tablets.These findings suggest that the tablet consisting of BSA-rGO-reinforced Br has encouraging potential for application in bone tissue engineering.
基金National Natural Science Foundations of China(Nos.30973105,31271035)Science and Technology Commission of Shanghai Municipality,China(No.11nm0506200)Ph.D.Programs Foundation of Ministry of Education of China(No.20130075110005)
文摘Colloidal gels made of oppositely charged nanoparticles are a novel class of hydrogels and can exhibit pseudoplastic behavior which will enable them to mold easily into specific shapes.These moldable gels can be used as building blocks to self-assemble into integral scaffolds from bottom to up through electrostatic forces.However,they are too weak to maintain scaffold morphology just depending on interparticle interactions such as Van der Waals attraction and electrostatic forces especially for bone tissue engineering.In this study,oppositely charged gelatin nanoparticles were firstly prepared by two-step desolvation method,followed by the mixture with water to form colloid gels.To solve the problem of weak mechanical performance of colloid gels, gelatin macromolecules were introduced into the prepared gels to form blend gels.The blend gels can be easily processed into three-dimensional( 3D) porous scaffolds via motor assisted microsyringe( MAM)system,a nozzle-based rapid prototyping technology,under mild conditions.After fabrication the scaffolds were crosslinked by glutaraldehyde( GA,25% solution in water by weight),then the crosslinked gelatin macromolecules network could form to improve the mechanical properties of colloid gels.The average particle size and zeta potential of gelatin nanoparticles were measured by NanoZS instrument.The morphology and microstructures of scaffolds were characterized by macroscopic images.The mechanical properties of the scaffolds were studied by a universal material testing machine.
文摘BACKGROUND Bone tissue engineering is an area of continued interest within orthopaedic surgery,as it promises to create implantable bone substitute materials that obviate the need for autologous bone graft.Recently,oxysterols–oxygenated derivatives of cholesterol-have been proposed as a novel class of osteoinductive small molecules for bone tissue engineering.Here,we present the first systematic review of the in vivo evidence describing the potential therapeutic utility of oxysterols for bone tissue engineering.AIM To systematically review the available literature examining the effect of oxysterols on in vivo bone formation.METHODS We conducted a systematic review of the literature following PRISMA guidelines.Using the PubMed/MEDLINE,Embase,and Web of Science databases,we queried all publications in the English-language literature investigating the effect of oxysterols on in vivo bone formation.Articles were screened for eligibility using PICOS criteria and assessed for potential bias using an expanded version of the SYRCLE Risk of Bias assessment tool.All full-text articles examining the effect of oxysterols on in vivo bone formation were included.Extracted data included:Animal species,surgical/defect model,description of therapeutic and control treatments,and method for assessing bone growth.Primary outcome was fusion rate for spinal fusion models and percent bone regeneration for critical-sized defect models.Data were tabulated and described by both surgical/defect model and oxysterol employed.Additionally,data from all included studies were aggregated to posit the mechanism by which oxysterols may mediate in vivo bone formation.RESULTS Our search identified 267 unique articles,of which 27 underwent full-text review.Thirteen studies(all preclinical)met our inclusion/exclusion criteria.Of the 13 included studies,5 employed spinal fusion models,2 employed critical-sized alveolar defect models,and 6 employed critical-sized calvarial defect models.Based upon SYRCLE criteria,the included studies were found to possess an overall“unclear risk of bias”;54%of studies reported treatment randomization and 38%reported blinding at any level.Overall,seven unique oxysterols were evaluated:20(S)-hydroxycholesterol,22(R)-hydroxycholesterol,22(S)-hydroxycholesterol,Oxy4/Oxy34,Oxy18,Oxy21/Oxy133,and Oxy49.All had statistically significant in vivo osteoinductive properties,with Oxy4/Oxy34,Oxy21/Oxy133,and Oxy49 showing a dose-dependent effect in some cases.In the eight studies that directly compared oxysterols to rhBMP-2-treated animals,similar rates of bone growth occurred in the two groups.Biochemical investigation of these effects suggests that they may be primarily mediated by direct activation of Smoothened in the Hedgehog signaling pathway.CONCLUSION Present preclinical evidence suggests oxysterols significantly augment in vivo bone formation.However,clinical trials are necessary to determine which have the greatest therapeutic potential for orthopaedic surgery patients.
文摘Tissue engineering’s main goal is to regenerate or replace tissues or organs that have been destroyed by disease,injury,or congenital disabilities.Tissue engineering now uses artificial supporting structures called scaffolds to restore damaged tissues and organs.These are utilized to attach the right cells and then grow them.Rapid prototyping appears to be the most promising technology due to its high level of precision and control.Bone tissue replacement“scaffolding”is a common theme discussed in this article.The fused deposition technique was used to construct our scaffold,and a polymer called polylactic acids and soybean oil resin were used to construct our samples.The samples were then divided into two groups;the first group was left without immersion in the simulated body fluid and served as a control for comparison.The second group was immersed in the simulated body fluid.The results of the Field Emission Scanning Electron Microscope(FESEM),Energy Dispersive X-ray Spectroscopy(EDX)and X-ray diffraction(XRD)were utilized to interpret the surface attachment to ions,elements,and compounds,giving us a new perspective on scaffold architecture.In this study,an innovative method has been used to print therapeutic scaffold that combines fused deposition three-dimensional printing with ultraviolet curing to create a high-quality biodegradable polymeric scaffold.Finally,the results demonstrate that adding soybean oil resin to the PLA increased ion attachment to the surface while also attracting tricalcium phosphate formation on the surface of the scaffold,which is highly promising in bone tissue replacement.In conclusion,the soybean oil resin,which is new in the field of bone tissue engineering,shows magnificent characteristics and is a good replacement biopolymer that replaces many ceramic and polymeric materials used in this field that have poor morphological characteristics.
基金Funded by the Postdoctor Science Fund of China (No. 20070410715) Shanghai Excellent Youth Special Fund (No. 17014)
文摘A novel method of designing and preparing bone tissue engineering scaffolds with controllable porous structure of both macro channels and micro pores was proposed. The CAD software UG NX3.0 was used to design the macro channels' shape, size and distribution. By integrating rapid prototyping and traditional porogen technique, the macro channels and micro pores were formed respectively. The size, shape and quantity of micro pores were controlled by porogen particulates. The sintered β-TCP porous scaffolds possessed connective macro channels of approximately 500 μm and micro pores of 200-400 μm. The porosity and connectivity of micro pores became higher with the increase of porogen ratio, while the mechanical properties weakened. The average porosity and compressive strength offl-TCP scaffolds prepared with porogen ratio of 60wt% were 78.12% and 0.2983 MPa, respectively. The cells' adhesion ratio of scaffolds was 67.43%. The ALP activity, OCN content and cells micro morphology indicated that cells grew and proliferated well on the scaffolds.
基金This work was supported by the National Natural Science Foundation of China(Grant No.U1601220)the National Natural Science Foundation of China(Grant No.82002310)+1 种基金the Chongqing Postgraduate Research and Innovation Project(Grant No.CYB20167)the Chongqing Postdoctoral Science Foundation(Grant No.csts2019jcyj-bsh0068).
文摘The limited bioactivity of scaffold materials is an important factor that restricts the development of bone tissue engineering.Wnt3a activates the classicWnt/β-catenin signaling pathway which effects bone growth and development by the accumulation ofβ-catenin in the nucleus.In this study,we fabricated 3D printed PCL scaffold with Wnt3a-induced murine bone marrow-derived stromal cell line ST2 decellularized matrix(Wnt3a-ST2-dCM-PCL)and ST2 decellularized matrix(ST2-dCM-PCL)by freeze-thaw cycle and DNase decellularization treatment which efficiently decellularized>90%DNA while preserved most protein.Compared to ST2-dCM-PCL,Wnt3a-ST2-dCM-PCL significantly enhanced newly-seeded ST2 proliferation,osteogenic differentiation and upregulated osteogenic marker genes alkaline phosphatase(Alp),Runx2,type I collagen(Col 1)and osteocalcin(Ocn)mRNA expression.After 14 days of osteogenic induction,Wnt3a-ST2-dCM-PCL promoted ST2 mineralization.These results demonstrated that Wnt3a-induced ST2 decellularized matrix improve scaffold materials’osteoinductivity and osteoconductivity.
基金National Natural Science Foundations of China(Nos.31271028,31570984)Innovation Program of Shanghai Municipal Education Commission,China(No.13ZZ051)+2 种基金International Cooperation Fund of the Science and Technology Commission of Shanghai Municipality,China(No.15540723400)Open Foundation of State Key Laboratory for Modification of Chemical Fibers and Polymer Materials,China(No.LK1416)“111 Project” Biomedical Textile Materials Science and Technology,China(No.B07024)
文摘The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/PCL)composite scaffold with porous structure was fabricated by thermally induced phase separation(TIPS).Dexamethasone(DEX)was incorporated into PLGA microspheres and then loaded on the PLLA/PLGA/PCL scaffoldtopreparethedesiredcompositescaffold.The physicochemical properties of the prepared composite scaffold were characterized.The morphology of rat bone marrow mesenchymal stem cells(BMSCs)grown on scaffolds was observed using scanning electron microscope(SEM)and fluorescence microscope.The resultsshowedthatthePLLA/PLGA/PCLscaffoldhad interconnected macropores and biomimetic nanofibrous structure.In addition,DEX can be released from scaffold in a sustained manner.More importantly,DEX loaded composite scaffold can effectively support the proliferation of BMSCs as indicated by fluorescence observation and cell proliferation assay.The results suggested that the prepared PLLA/PLGA/PCL composite scaffold incorporating drug-loaded PLGA microspheres could hold great potential for bone tissue engineering applications.
基金National Natural Science Foundations of China(Nos.31771048,31570984,31271028)International Cooperation Fund of the Science and Technology Commission of Shanghai Municipality,China(No.15540723400)+1 种基金Innovation Foundation of Donghua University,China(No.EG2017012)Biomedical Textile Materials Science and Technology(111 Project),China(No.B07024)
文摘The customized implants which are composed of polycaprolactone( PCL) and strontium substituted nanohydroxyapatite( SrHA) were fabricated successfully by using fused deposition modeling( FDM),which is a simple 3 D printing technology for fabricating personalized products. The physical and chemical properties of composite scaffolds were characterized by transmission electron microscopy( TEM), Fourier transform infrared spectroscopy( FTIR), X-Ray diffraction( XRD) and inductively coupled plasma-atomic emission spectroscopy( ICPAES). The results suggested that strontium element was successfully doped into nanohydroxyapatite and all scaffolds showed the homogeneous network structure. Furthermore, the in vitro biocompatibility of the scaffolds was evaluated by cell counting kit-8( CCK-8) assay. The data indicated that the prepared scaffolds exhibited excellent biocompatibility to bone marrow mesenchymal stem cells( BMSCs). Besides,strontium element can be released from PCL-SrHA scaffolds in a sustained manner. Therefore,the 3 D printing PCL-SrHA scaffolds hold great potential for bone tissue engineering.
基金by research grants from the Natural Science Foundation of China(82102696 to JF)the Chongqing Bayu Young Scholar Award(JF),the 2019 Chongqing Support Program for Entrepreneurship and Innovation(No.cx2019113 to JF)+4 种基金the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298 to JF),the National Institutes of Health(CA226303 to TCH,and DE030480 to RRR)supported by the Medical Scientist Training Program of the National Institutes of Health(T32 GM007281)supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1TR002389-07.
文摘Effective bone regeneration through tissue engineering requires a combination of osteogenic progenitors,osteoinductive biofactors and biocompatible scaffold materials.Mesenchymal stem cells(MSCs)represent the most promising seed cells for bone tissue engineering.As multipotent stem cells that can self-renew and differentiate into multiple lineages including bone and fat,MSCs can be isolated from numerous tissues and exhibit varied differentiation potential.To identify an optimal progenitor cell source for bone tissue engineering,we analyzed the proliferative activity and osteogenic potential of four commonly-used mouse MSC sources,including immortalized mouse embryonic fibroblasts(iMEF),immortalized mouse bone marrow stromal stem cells(imBMSC),immortalized mouse calvarial mesenchymal progenitors(iCAL),and immortalized mouse adipose-derived mesenchymal stem cells(iMAD).We found that iMAD exhibited highest osteogenic and adipogenic capabilities upon BMP9 stimulation in vitro,whereas iMAD and iCAL exhibited highest osteogenic capability in BMP9-induced ectopic osteogenesis and critical-sized calvarial defect repair.Transcriptomic analysis revealed that,while each MSC line regulated a distinct set of target genes upon BMP9 stimulation,all MSC lines underwent osteogenic differentiation by regulating osteogenesis-related signaling including Wnt,TGF-β,PI3K/AKT,MAPK,Hippo and JAK-STAT pathways.Collectively,our results demonstrate that adipose-derived MSCs represent optimal progenitor sources for cell-based bone tissue engineering.
基金supported by National Natural Science Foundation of China (31971326)Science and Technology Project of Suzhou (ZXT2022007).
文摘Bone fractures are common occurrence in clinical settings,creating a high demand for effective repair material.Unfortunately,limited graft availability,donor site morbidities,unpredictable clinical outcomes,immunologic reactions,infection risks,and geometrical mismatching concerns hampered tissue graft use and underscored the need for scaffolds for more effective bone reconstructions due to their tunable properties.Significant progress has been carried out in past decade in the fields of nanoceramics synthesis,bioconjugate chemistry,and composite material processing.This review outlines hierarchical structures and biology of bone tissue,materialistic compo-nents of scaffolds(bioceramics,polymers,bioactive drugs),featured scaffolding strategies(nanofibers,hydrogels,aerogels,bioprinting,and fiber-reinforced composite),and emphasis that hierarchical and physiochemical char-acteristics of bone should be used as an inspiration for scaffold design.This review discussed how differences in materiobiological aspects of scaffolds,such as polymer/bioceramic nanocomposite,mineralized nanocomposite,matrix-rich nanocomposite,3D microenvironmental cues,pore space cues,mechanical cues,usage of physical stimulation(magnetic,electroactive,and photoactivated cues),surface cues(wettability,roughness,textured,and surface charge),and biointerface cues(cell-biomaterial interactions,cell-selective homing,and cell regula-tory strategies)modulate cellular and biological response for bone tissue engineering.This study further outlines the challenges and benefits of integrating materiobiological cues of scaffolds for bone tissue engineering.
基金supported by the National Natural Science Foundation of China(Grant Nos.12202302,12272253,and 82103147)The support of the Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province(Grant No.20220006)was also acknowledged with gratitude.
文摘In the field of bone defect repair,critical requirements for favorable cytocompatibility and optimal mechanical properties have propelled research efforts towards the development of composite materials.In this study,carbon nanotubes/polylactic acid/hydroxyapatite(CNTs/PLA/HA)scaffolds with different contents(0.5,1,1.5 and 2 wt.%)of CNTs were prepared by the thermally induced phase separation(TIPS)method.The results revealed that the composite scaffolds had uniform pores with high porosities over 68%and high through performances.The addition of CNTs significantly enhanced the mechanical properties of resulted PLA/HA,in which the 1.5 wt.%CNTs/PLA/HA composite scaffold demonstrated the optimum mechanical behaviors with the bending elastic modulus of(868.5±12.34)MPa,the tensile elastic modulus of(209.51±12.73)MPa,and the tensile strength of(3.26±0.61)MPa.Furthermore,L929 cells on the 1.5 wt.%CNTs/PLA/HA scaffold displayed good spreading performance and favorable cytocompatibility.Therefore,it is expected that the 1.5 wt.%CNTs/PLA/HA scaffold has potential applications in bone tissue engineering.