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
In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we dev...In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.展开更多
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
The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bon...The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.展开更多
Background:There is a deficiency of bibliometric and visually represented analysis in research on the immunological related variables involved in bone tissue regeneration.Using bibliometric and visual analysis,this st...Background:There is a deficiency of bibliometric and visually represented analysis in research on the immunological related variables involved in bone tissue regeneration.Using bibliometric and visual analysis,this study sought to thoroughly examine the hotspots and future directions in the investigation of immunological important variables in bone tissue regeneration.Methods:The Web of Science Core Collection(WoSCC)database was searched and a collection of published works on the subject of immunological related factors in bone tissue regeneration between 2000 and 2021 was generated.The data chosen from the WoSCC were then subjected to a systematic bibliometric and visualized analysis using the online bibliometric analytics system,Apache ECharts,VOSviewer,Bibliographic Items Co-occurrence Matrix Builder 2.0,and Gcluto 1.0.Results:For this investigation,1,088 publications on the involvement of immune related components in bone tissue regeneration were chosen.Between 2000 and 2021,China maintained its supremacy in global research on the function of immune related components in bone tissue regeneration.Shanghai Jiao Tong University is the most productive institution.Biomaterials has published the most publications on the involvement of immune-related components in bone tissue regeneration.Xiao Y,Schmidt-Bleek K,and Ignatius A all played important roles in the study of immune-related variables in bone tissue regeneration.Research on the role of immune relevant factors in bone tissue regeneration has identified five hotspots:(1)macrophage-based immunomodulation on osteogenesis of mesenchymal stem cells(MSCs);(2)biomaterials for bone repair in bone tissue engineering;(3)osteoimmunomodulation mediated by inflammation and macrophages during bone healing;(4)osteoimmunomodulation in angiogenesis during bone regeneration;and(5)the effect of macrophage polarization regulated by bone tissue engineering on osteogenic differentiation of MSCs as bone tissue.Conclusion:This study represents the first-ever bibliometric and visualized examination of how immune factors contribute to bone tissue regeneration.The focus and forthcoming direction in bone regeneration research will be on macrophage-driven immunomodulation in the process of bone regeneration.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
The experimental research, presented in this study, focuses on athletic tests with the purpose to highlight the elastic deformations of the bones of the lower limbs, intending to verify whether the manually treated an...The experimental research, presented in this study, focuses on athletic tests with the purpose to highlight the elastic deformations of the bones of the lower limbs, intending to verify whether the manually treated anatomical structure increases in elasticity, becoming able to accumulate more energy in the loading phase, to then release it in the final phase of the thrust. Introduction: Too often neglected, the bone tissue is capable of deforming. The deformation has a key role in the cushioning and dissipation of stress, a function that is hindered in the event of fascial tension, which will consequently fall on other structures used for the same purpose (Discs, menisci, cartilage, …). Structures that, in the event of increased mechanical stress, could undergo degeneration, inflammation, and injury. Materials and Method: Randomized double-blind selection of 38 people, 18 in the treatment group and 20 in the control group, men and women, aged between 16 and 35, who have been part, for at least one year, of a sports club, with a large space dedicated to jumping in its training program, have been divided into two groups: the treatment group, which was treated to increase the performance of the jump and the control group subjected to mild manual pressures, without any intention. Results: The treatment group had an increase in Standing Long Jump (SLJ) for 3.67% (p Conclusions: This study has shown that an osteopathic manipulative treatment, aimed at increasing jumping performance, can increase the performance of the SLJ.展开更多
Calcium-based biocomposite materials have a pivotal role in the biomedical field with their diverse properties and applications in combating challenging medical problems. The study states the development and character...Calcium-based biocomposite materials have a pivotal role in the biomedical field with their diverse properties and applications in combating challenging medical problems. The study states the development and characterization of Calcium-based biocomposites: Hydroxyapatite (HAP), and PVA-Gelatin-HAP films. For the preparation of Calcium-based biocomposites, an unconventional source, the waste material calcite stone, was used as calcium raw material, and by the process of calcination, calcium oxide was synthesized. From calcium oxide, HAP was prepared by chemical precipitation method, which was later added in different proportions to PVA-Gelatin solution and finally dried to form biocomposite films. Then the different properties of PVA/Gelatin/HAP composite, for instance, chemical, mechanical, thermal, and swelling properties due to the incorporation of various proportions of HAP in PVA-Gelatin solution, were investigated. The characterization of the HAP was conducted by X-ray Diffraction Analysis, and the characterization of HAP-PVA-Gelatin composites was done by Fourier Transform Infrared Spectroscopy, Thermomechanical Analysis, Tensile test, Thermogravimetric Differential Thermal Analysis, and Swelling Test. The produced biocomposite films might have applications in orthopedic implants, drug delivery, bone tissue engineering, and wound healing.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
Objective To evaluate the feasibility of whole body diffusion weighted imaging (DWI) in bone metastasis detection using bone scintigraphy as comparison. Methods Forty-five patients with malignancy history were enrolle...Objective To evaluate the feasibility of whole body diffusion weighted imaging (DWI) in bone metastasis detection using bone scintigraphy as comparison. Methods Forty-five patients with malignancy history were enrolled in our study. All the patients received the whole body DWI and bone scintigraphy scan within 1 week. The magnetic resonance (MR) examination was performed on 3.0T MR scanner using embedded body coil. The images were reviewed separately by two radiologists and two nuclear medicine physicians, who were blinded to the results of the other imaging modality. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the two techniques for detecting bone metastasis were analyzed. Results A total of 181 metastatic lesions in 77 regions of 34 patients were detected by whole body DWI, and 167 metastatic lesions in 76 regions of 31 patients were identified by bone scintigraphy. The patient-based sensitivity and PPV of whole body DWI and bone scintigraphy were similar (89.5% vs. 81.6%, 97.1% vs. 91.2%), whereas, the patient-based specificity and NPV of whole body DWI were obviously higher than those of bone scintigraphy (85.7% vs. 57.1%, 60.0% vs. 36.4%). Ten regions negative in scintigraphy but positive in whole body DWI, mainly located in spine, pelvis, and femur; nine regions only detected by scintigraphy, mainly located in skull, sternum, clavicle, and scapula. The region-based sensitivity and specificity of whole body DWI were slightly higher than those of bone scintigraphy (89.5% vs. 88.4%, 95.6% vs. 87.6%). Conclusion Whole body DWI reveals excellent concordance with bone scintigraphy regarding detection of bone metastasis, and the two techniques are complementary for each other.展开更多
To investigate the osteoinductive and ectopicly osteogenic effects of a novel peptide P24 derived from bone morphogenetic protein 2 (BMP2), biodegradable collagen scaffolds (CS) were used to load BMP-2-derived pep...To investigate the osteoinductive and ectopicly osteogenic effects of a novel peptide P24 derived from bone morphogenetic protein 2 (BMP2), biodegradable collagen scaffolds (CS) were used to load BMP-2-derived peptide solutions with different concentrations (0.4 mg peptide/CS, 0.1 mg peptide/CS and pure CS, respectively), and the implants were implanted into muscular pockets on the back of Wistar rats. Radiographs and histological analysis were performed to evaluate the ectopic bone effects. Active ectopic bone formation was seen in both groups containing the peptide at different concentration (0.4 mg and 0.1 mg), whereas no bone formation and only fibrous tissue was seen in the pure CS group. The new bone formation induced by the peptide P24 displayed a dose-dependent and time-dependent efficiency. The new bone formation in the 0.4 mg peptide/CS group significantly increased than that of the 0.1 mg peptide/CS group. This novel BMP-2-derived peptide had excellent osteoinductive and ectopicly osteogenic properties which were similar to those of BMP2.展开更多
The biocompatibility and osteogenic activity of allogenic decalcified bone matrix (DBM) used as a carrier for bone tissue engineering were studied. Following the method described by Urist, allogenic DBM was made. In v...The biocompatibility and osteogenic activity of allogenic decalcified bone matrix (DBM) used as a carrier for bone tissue engineering were studied. Following the method described by Urist, allogenic DBM was made. In vitro, DBM and bone marrow stromal cell (BMSC) from rabbits were co-cultured for 3-7 days and subjected to HE staining, and a series of histomorphological observations were performed under phase-contrast microscopy and scanning electron microscopy (SEM). In vivo the mixture of DBM/BMSC co-cultured for 3 days was planted into one side of muscules sacrospinalis of rabbits, and the DBM without BMSC was planted into other side as control. Specimens were collected at postoperative week 1, 2 and 4, and subjected to HE staining, and observed under SEM. The results showed during culture in vitro, the BMSCs adherent to the wall of DBM grew, proliferated and had secretive activity. The in vivo experiment revealed that BMSCs and undifferentiated mesenchymal cells in the perivascular region invaded gradually and proliferated together in DBM/BMSC group, and colony-forming units of chondrocytes were found. Osteoblasts, trabecular bone and medullary cavity appeared. The inflammatory reaction around muscles almost disappeared at the second weeks. In pure DBM group, the similar changes appeared from the surface of the DBM to center, and the volume of total regenerate bones was less than the DBM/BMSC group at the same time. The results indicated that the mixture of DBM and BMSC had good biocompatibility and ectopic induced osteogenic activity.展开更多
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
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 effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing ...The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor (VDR), we examined their response to different concentrations of 25-hydroxy vitamin D3 [25(OH)D3] (100 or 500 nmol·L^-1) and 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] (0.1 or 0.5 nmol·L^-1) metabolites in cell cultures. Specifically, CD14+ monocytes were cultured in charcoal-stripped serum in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Tartrate-resistant acid phosphatase (TRAP) histochemical staining assays and dentine resorption analysis were used to identify the size and number of osteoclast cells, number of nuclei per cell and resorption activity. The expression of VDR was detected in human bone tissue (ex vivo) by immunohistochemistry and in vitro cell cultures by western blotting. Quantitative reverse transcription-PCR (qRT-PCR) was used to determine the level of expression of vitamin D-related genes in response to vitamin D metabolites. VDR-related genes during osteoclastogenesis, shown by qRT-PCR, was stimulated in response to 500 nmol·L^-1 of 25(OH)D3 and 0.1-0.5 nmol·L^-1 of 1,25(OH)2D3, upregulating cytochrome P450 family 27 subfamily B member I (CYP27B1) and cytochrome P450 family 24 subfamily A member I (CYP24A1). Osteoclast fusion transcripts transmembrane 7 subfamily member 4 (tm7sf4) and nuclear factor of activated T-cell cytoplasmic 1 (nfatcl) where downregulated in response to vitamin D metabolites. Osteoclast number and resorption activity were also increased. Both 25(OH)D3 and 1,25(OH)2D3 reduced osteoclast size and number when co-treated with RANKL and M-CSF. The evidence for VDR expression in resorbing osteoclasts in vivo and low-dose effects of 1,25(OH)2D3 on osteoclasts in vitro may therefore provide insight into the effects of clinical vitamin D treatments, further providing a counterpoint to the high-dose effects reported from in vitro experiments.展开更多
As a bone scaffold,meeting all basic requirements besides dealing with other bone-related issues-bone cancer and accelerated regeneration-is not expected from traditional scaffolds,but a newer class of scaffolds calle...As a bone scaffold,meeting all basic requirements besides dealing with other bone-related issues-bone cancer and accelerated regeneration-is not expected from traditional scaffolds,but a newer class of scaffolds called multifunctional.From a clinical point of view,being a multifunctional scaffold means reducing in healing time,direct costs-medicine,surgery,and hospitalization-and indirect costs-loss of mobility,losing job,and pain.The main aim of the present review is following the multifunctional bone scaffolds trend to deal with both bone regeneration and cancer therapy.Special consideration is given to different fabrication techniques which have been applied to yield these materials spanning from traditional to modern ones.Moreover,the hierarchical structure of bone plus bone cancers and available medicines to them are introduced to familiarize the potential reader of review with the pluri-disciplinary essence of the field.Eventually,a brief discussion relating to the future trend of these materials is provided.展开更多
Objectives To construct the cancellous bone explant model and a method of culturing these bone tissues in vitro, and to investigate the effect of mechanical load on growth of cancellous bone tissue in vtro. Methods C...Objectives To construct the cancellous bone explant model and a method of culturing these bone tissues in vitro, and to investigate the effect of mechanical load on growth of cancellous bone tissue in vtro. Methods Cancellous bone were extracted from rabbit femoral head and cut into I-ram-thick and 8-ram-diameter slices under sterile conditions. HE staining and scanning electron microscopy were employed to identify the histomorphology of the model after being cultured with a new dynamic load and circulating perfusion bioreactor system for 0, 3, 5, and 7 days, respectively. We built a three-dimensional model using microCT and analyzed the loading effects using finite element analysis. The model was subjected to mechanical load of 1000, 2000, 3000, and 4000 με respectively for 30 minutes per day. After 5 days of continuous stimuli, the activities of alkaline phosphatase (AKP) and tartrate-resistant acid phosphatase (TRAP) were detected. Apoptosis was analyzed by DNA ladder detection and caspase-3/8/9 activity detection. Results After being cultured for 3, 5, and 7 days, the bone explant model grew well. HE staining showed the apparent nucleus in cells at the each indicated time, and electron microscope revealed the living cells in the bone tissue. The activities of AKP and TRAP in the bone explant model under mechanical load of 3000 and 4000 με were significantly lower than those in the unstressed bone tissues (all P〈0.05). DNA ladders were seen in the bone tissue under 3000 and 4000με mechanical load. Moreover, there was significant enhancement in the activities of caspase-3/8/9 in the mechanical stress group of 3000 and 4000 με (all P〈0.05). Conclusions The cancellous bone explant model extracted from the rabbit femoral head could be alive at least for 7 days in the dynamic load and circulating perfusion bioreactor system, however, pathological mechanical load could affect the bone tissue growth by apoptosis in vitro. The differentiation of osteobiasts and osteoclasts might be inhibited after the model is stimulated by mechanical load of 3000 and 4000 με.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.
基金supported by the National Key R&D Program of China[grant number 2021YFC2400700]the National Natural Science Foundation of China[grant numbers 82170929,81970908 and 81771039].
文摘In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.
文摘Nonunion represents a crucial challenge in orthopedic medicine,demanding innovative solutions beyond the scope of traditional bone grafting methods.Among the various strategies available,magnesium(Mg)implants have been recognized for their biocompatibility and biodegradability.However,their susceptibility to rapid corrosion and degradation has garnered notable research interest in bone tissue engineering(BTE),particularly in the development of Mg-incorporated biocomposite scaffolds.These scaffolds gradually release Mg2+,which enhances immunomodulation,osteogenesis,and angiogenesis,thus facilitating effective bone regeneration.This review presents myriad fabrication techniques used to create Mg-incorporated biocomposite scaffolds,including electrospinning,three-dimensional printing,and sol-gel synthesis.Despite these advancements,the application of Mg-incorporated biocomposite scaffolds faces challenges such as controlling the degradation rate of Mg and ensuring mechanical stability.These limitations highlight the necessity for ongoing research aimed at refining fabrication techniques to better regulate the physicochemical and osteogenic properties of scaffolds.This review provides insights into the potential of Mg-incorporated biocomposite scaffolds for BTE and the challenges that need to be addressed for their successful translation into clinical applications.
基金Supported by the National Key Research and Development Program of China,No.2023YFC2508806Key Research and Development Project in Henan Province,No.231111310500+4 种基金Young Elite Scientists Sponsorship Program by CAST,No.2021-QNRC2-A06Scientific Research Project of Henan Zhongyuan Medical Science and Technology Innovation and Development Foundation,No.ZYYC2023ZDYouth Science Award Project of the Provincial-Level Joint Fund for Science and Technology Research and Development Project in Henan Province,No.225200810084Special Project on Training Top Talents in Traditional Chinese Medicine in Henan Province,No.2022ZYBJ242023 Hunan University of Chinese Medicine Postgraduate Innovation Project,No.2023CX64。
文摘The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.
文摘Background:There is a deficiency of bibliometric and visually represented analysis in research on the immunological related variables involved in bone tissue regeneration.Using bibliometric and visual analysis,this study sought to thoroughly examine the hotspots and future directions in the investigation of immunological important variables in bone tissue regeneration.Methods:The Web of Science Core Collection(WoSCC)database was searched and a collection of published works on the subject of immunological related factors in bone tissue regeneration between 2000 and 2021 was generated.The data chosen from the WoSCC were then subjected to a systematic bibliometric and visualized analysis using the online bibliometric analytics system,Apache ECharts,VOSviewer,Bibliographic Items Co-occurrence Matrix Builder 2.0,and Gcluto 1.0.Results:For this investigation,1,088 publications on the involvement of immune related components in bone tissue regeneration were chosen.Between 2000 and 2021,China maintained its supremacy in global research on the function of immune related components in bone tissue regeneration.Shanghai Jiao Tong University is the most productive institution.Biomaterials has published the most publications on the involvement of immune-related components in bone tissue regeneration.Xiao Y,Schmidt-Bleek K,and Ignatius A all played important roles in the study of immune-related variables in bone tissue regeneration.Research on the role of immune relevant factors in bone tissue regeneration has identified five hotspots:(1)macrophage-based immunomodulation on osteogenesis of mesenchymal stem cells(MSCs);(2)biomaterials for bone repair in bone tissue engineering;(3)osteoimmunomodulation mediated by inflammation and macrophages during bone healing;(4)osteoimmunomodulation in angiogenesis during bone regeneration;and(5)the effect of macrophage polarization regulated by bone tissue engineering on osteogenic differentiation of MSCs as bone tissue.Conclusion:This study represents the first-ever bibliometric and visualized examination of how immune factors contribute to bone tissue regeneration.The focus and forthcoming direction in bone regeneration research will be on macrophage-driven immunomodulation in the process of bone regeneration.
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.
文摘The experimental research, presented in this study, focuses on athletic tests with the purpose to highlight the elastic deformations of the bones of the lower limbs, intending to verify whether the manually treated anatomical structure increases in elasticity, becoming able to accumulate more energy in the loading phase, to then release it in the final phase of the thrust. Introduction: Too often neglected, the bone tissue is capable of deforming. The deformation has a key role in the cushioning and dissipation of stress, a function that is hindered in the event of fascial tension, which will consequently fall on other structures used for the same purpose (Discs, menisci, cartilage, …). Structures that, in the event of increased mechanical stress, could undergo degeneration, inflammation, and injury. Materials and Method: Randomized double-blind selection of 38 people, 18 in the treatment group and 20 in the control group, men and women, aged between 16 and 35, who have been part, for at least one year, of a sports club, with a large space dedicated to jumping in its training program, have been divided into two groups: the treatment group, which was treated to increase the performance of the jump and the control group subjected to mild manual pressures, without any intention. Results: The treatment group had an increase in Standing Long Jump (SLJ) for 3.67% (p Conclusions: This study has shown that an osteopathic manipulative treatment, aimed at increasing jumping performance, can increase the performance of the SLJ.
文摘Calcium-based biocomposite materials have a pivotal role in the biomedical field with their diverse properties and applications in combating challenging medical problems. The study states the development and characterization of Calcium-based biocomposites: Hydroxyapatite (HAP), and PVA-Gelatin-HAP films. For the preparation of Calcium-based biocomposites, an unconventional source, the waste material calcite stone, was used as calcium raw material, and by the process of calcination, calcium oxide was synthesized. From calcium oxide, HAP was prepared by chemical precipitation method, which was later added in different proportions to PVA-Gelatin solution and finally dried to form biocomposite films. Then the different properties of PVA/Gelatin/HAP composite, for instance, chemical, mechanical, thermal, and swelling properties due to the incorporation of various proportions of HAP in PVA-Gelatin solution, were investigated. The characterization of the HAP was conducted by X-ray Diffraction Analysis, and the characterization of HAP-PVA-Gelatin composites was done by Fourier Transform Infrared Spectroscopy, Thermomechanical Analysis, Tensile test, Thermogravimetric Differential Thermal Analysis, and Swelling Test. The produced biocomposite films might have applications in orthopedic implants, drug delivery, bone tissue engineering, and wound healing.
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Objective To evaluate the feasibility of whole body diffusion weighted imaging (DWI) in bone metastasis detection using bone scintigraphy as comparison. Methods Forty-five patients with malignancy history were enrolled in our study. All the patients received the whole body DWI and bone scintigraphy scan within 1 week. The magnetic resonance (MR) examination was performed on 3.0T MR scanner using embedded body coil. The images were reviewed separately by two radiologists and two nuclear medicine physicians, who were blinded to the results of the other imaging modality. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the two techniques for detecting bone metastasis were analyzed. Results A total of 181 metastatic lesions in 77 regions of 34 patients were detected by whole body DWI, and 167 metastatic lesions in 76 regions of 31 patients were identified by bone scintigraphy. The patient-based sensitivity and PPV of whole body DWI and bone scintigraphy were similar (89.5% vs. 81.6%, 97.1% vs. 91.2%), whereas, the patient-based specificity and NPV of whole body DWI were obviously higher than those of bone scintigraphy (85.7% vs. 57.1%, 60.0% vs. 36.4%). Ten regions negative in scintigraphy but positive in whole body DWI, mainly located in spine, pelvis, and femur; nine regions only detected by scintigraphy, mainly located in skull, sternum, clavicle, and scapula. The region-based sensitivity and specificity of whole body DWI were slightly higher than those of bone scintigraphy (89.5% vs. 88.4%, 95.6% vs. 87.6%). Conclusion Whole body DWI reveals excellent concordance with bone scintigraphy regarding detection of bone metastasis, and the two techniques are complementary for each other.
基金the National Natural Science Foundation of China(No.30200063,30070483,301070270)the Program for New Century Excellent Talents in University from the Ministry of Education of China,and the Excellent Youth Foundation of Wuhan Science and Technology Committee(No.20005006071-10)
文摘To investigate the osteoinductive and ectopicly osteogenic effects of a novel peptide P24 derived from bone morphogenetic protein 2 (BMP2), biodegradable collagen scaffolds (CS) were used to load BMP-2-derived peptide solutions with different concentrations (0.4 mg peptide/CS, 0.1 mg peptide/CS and pure CS, respectively), and the implants were implanted into muscular pockets on the back of Wistar rats. Radiographs and histological analysis were performed to evaluate the ectopic bone effects. Active ectopic bone formation was seen in both groups containing the peptide at different concentration (0.4 mg and 0.1 mg), whereas no bone formation and only fibrous tissue was seen in the pure CS group. The new bone formation induced by the peptide P24 displayed a dose-dependent and time-dependent efficiency. The new bone formation in the 0.4 mg peptide/CS group significantly increased than that of the 0.1 mg peptide/CS group. This novel BMP-2-derived peptide had excellent osteoinductive and ectopicly osteogenic properties which were similar to those of BMP2.
文摘The biocompatibility and osteogenic activity of allogenic decalcified bone matrix (DBM) used as a carrier for bone tissue engineering were studied. Following the method described by Urist, allogenic DBM was made. In vitro, DBM and bone marrow stromal cell (BMSC) from rabbits were co-cultured for 3-7 days and subjected to HE staining, and a series of histomorphological observations were performed under phase-contrast microscopy and scanning electron microscopy (SEM). In vivo the mixture of DBM/BMSC co-cultured for 3 days was planted into one side of muscules sacrospinalis of rabbits, and the DBM without BMSC was planted into other side as control. Specimens were collected at postoperative week 1, 2 and 4, and subjected to HE staining, and observed under SEM. The results showed during culture in vitro, the BMSCs adherent to the wall of DBM grew, proliferated and had secretive activity. The in vivo experiment revealed that BMSCs and undifferentiated mesenchymal cells in the perivascular region invaded gradually and proliferated together in DBM/BMSC group, and colony-forming units of chondrocytes were found. Osteoblasts, trabecular bone and medullary cavity appeared. The inflammatory reaction around muscles almost disappeared at the second weeks. In pure DBM group, the similar changes appeared from the surface of the DBM to center, and the volume of total regenerate bones was less than the DBM/BMSC group at the same time. The results indicated that the mixture of DBM and BMSC had good biocompatibility and ectopic induced osteogenic activity.
基金supported by 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 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financial support from Orthopaedic Research UK (P 470)Arthritis Research UK (grant 20299 and Oxford EOTC)
文摘The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor (VDR), we examined their response to different concentrations of 25-hydroxy vitamin D3 [25(OH)D3] (100 or 500 nmol·L^-1) and 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] (0.1 or 0.5 nmol·L^-1) metabolites in cell cultures. Specifically, CD14+ monocytes were cultured in charcoal-stripped serum in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Tartrate-resistant acid phosphatase (TRAP) histochemical staining assays and dentine resorption analysis were used to identify the size and number of osteoclast cells, number of nuclei per cell and resorption activity. The expression of VDR was detected in human bone tissue (ex vivo) by immunohistochemistry and in vitro cell cultures by western blotting. Quantitative reverse transcription-PCR (qRT-PCR) was used to determine the level of expression of vitamin D-related genes in response to vitamin D metabolites. VDR-related genes during osteoclastogenesis, shown by qRT-PCR, was stimulated in response to 500 nmol·L^-1 of 25(OH)D3 and 0.1-0.5 nmol·L^-1 of 1,25(OH)2D3, upregulating cytochrome P450 family 27 subfamily B member I (CYP27B1) and cytochrome P450 family 24 subfamily A member I (CYP24A1). Osteoclast fusion transcripts transmembrane 7 subfamily member 4 (tm7sf4) and nuclear factor of activated T-cell cytoplasmic 1 (nfatcl) where downregulated in response to vitamin D metabolites. Osteoclast number and resorption activity were also increased. Both 25(OH)D3 and 1,25(OH)2D3 reduced osteoclast size and number when co-treated with RANKL and M-CSF. The evidence for VDR expression in resorbing osteoclasts in vivo and low-dose effects of 1,25(OH)2D3 on osteoclasts in vitro may therefore provide insight into the effects of clinical vitamin D treatments, further providing a counterpoint to the high-dose effects reported from in vitro experiments.
文摘As a bone scaffold,meeting all basic requirements besides dealing with other bone-related issues-bone cancer and accelerated regeneration-is not expected from traditional scaffolds,but a newer class of scaffolds called multifunctional.From a clinical point of view,being a multifunctional scaffold means reducing in healing time,direct costs-medicine,surgery,and hospitalization-and indirect costs-loss of mobility,losing job,and pain.The main aim of the present review is following the multifunctional bone scaffolds trend to deal with both bone regeneration and cancer therapy.Special consideration is given to different fabrication techniques which have been applied to yield these materials spanning from traditional to modern ones.Moreover,the hierarchical structure of bone plus bone cancers and available medicines to them are introduced to familiarize the potential reader of review with the pluri-disciplinary essence of the field.Eventually,a brief discussion relating to the future trend of these materials is provided.
基金Supported by grants from the National Natural Science Foundation Key Project of China(10832012)the National Natural Science Foundation of China(31370942 and 11072266)
文摘Objectives To construct the cancellous bone explant model and a method of culturing these bone tissues in vitro, and to investigate the effect of mechanical load on growth of cancellous bone tissue in vtro. Methods Cancellous bone were extracted from rabbit femoral head and cut into I-ram-thick and 8-ram-diameter slices under sterile conditions. HE staining and scanning electron microscopy were employed to identify the histomorphology of the model after being cultured with a new dynamic load and circulating perfusion bioreactor system for 0, 3, 5, and 7 days, respectively. We built a three-dimensional model using microCT and analyzed the loading effects using finite element analysis. The model was subjected to mechanical load of 1000, 2000, 3000, and 4000 με respectively for 30 minutes per day. After 5 days of continuous stimuli, the activities of alkaline phosphatase (AKP) and tartrate-resistant acid phosphatase (TRAP) were detected. Apoptosis was analyzed by DNA ladder detection and caspase-3/8/9 activity detection. Results After being cultured for 3, 5, and 7 days, the bone explant model grew well. HE staining showed the apparent nucleus in cells at the each indicated time, and electron microscope revealed the living cells in the bone tissue. The activities of AKP and TRAP in the bone explant model under mechanical load of 3000 and 4000 με were significantly lower than those in the unstressed bone tissues (all P〈0.05). DNA ladders were seen in the bone tissue under 3000 and 4000με mechanical load. Moreover, there was significant enhancement in the activities of caspase-3/8/9 in the mechanical stress group of 3000 and 4000 με (all P〈0.05). Conclusions The cancellous bone explant model extracted from the rabbit femoral head could be alive at least for 7 days in the dynamic load and circulating perfusion bioreactor system, however, pathological mechanical load could affect the bone tissue growth by apoptosis in vitro. The differentiation of osteobiasts and osteoclasts might be inhibited after the model is stimulated by mechanical load of 3000 and 4000 με.