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Objectives:To observe the repair effect of AKE/GB30 mesh cage loaded with naringin in spinal bone defect model,and explore the mechanism of this biomaterial based on bone morphogenetic proteins(BMPs)-vascular endothelial growth factor(VEGF)signal pathway.Methods:A dental drill was used to make a 7mmx5mmx4mm spinal bone defect model between L5 and L6 vertebrae in 30 New Zealand male rabbits,and AKE/GB30 mesh cages were prepared.The biomechanical properties of AKE/GB30 mesh cages loaded with naringin were tested,and their in vitro drug release behavior was measured.New Zealand rabbits that were successfully modeled were randomly divided into three groups using a randomly digital table method,namely,blank group,autologous bone graft group,and bone graft biomaterial+naringin combined group.Except the blank group,autologous bone transplantation and AKE/GB30 mesh cage loaded with naringin were used for repair.At 6 weeks and 12 weeks after surgery,5 rabbits were taken from each group,and the bone repair status[including bone volume/tissue volume(BV/TV),bone trabecular thickness(Tb.Th)and bone trabecular number(Tb.N)]were detected by micro computed tomography(Micro CD.Real-time fluorescence quantitative polymerase chain reaction(RT-PCR)was used to detect the expressions of bone morphogenetic protein 2(BMP2),VEGF,Runt related transcription factor 2(RUNX2),alkaline phosphatase(ALP),and osteocalcin(OCN)messenger ribonucleic acid(mRNA).Immunoblotting assay(WB)was used to detect the expressions of BMP2,VEGF,RUNX2,ALP,and OCN proteins in bone tissues.Results:AKE/GB30 mesh cages had been successfully manufactured,and its characteristic testing results met the requirements for repairing spinal bone defects.The AKE/GB30 mesh cage loaded with naringin had a maximum compressive strength of 28MPa and a maximum resistance pressure of 15N.At 6 weeks,its cumulative release rate reached(98.15±1.47)％.After 12 weeks,the BV/TV,Tb.Th,and Tb.N,as well as the mRNA and protein expressions of BMP2,VEGF,RUNX2,ALP,and OCN in bone tissues of each group were higher than those after 6 weeks(P＜0.05).The above indicators in the autologous bone graft group and the bone graft biomaterial+naringin combined group were higher than those in the blank group(P＜0.05),and there were no significant differences in the above indicators between the autologous bone graft group and the bone graft biomaterial+naringin combined group(P＞0.05).Conclusions:The effect of AKE/GB30 cage loaded with naringin in repairing spinal bone defect models is equivalent to that of autologous bone graft,which is presumed to achieve by promoting the expressions of BMP2,VEGF,RUNX2,ALP,and OCN.
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Objective:To investigate the clinical outcomes and efficacy of trabecular metal (TM) cones for the reconstruction of metaphyseal bone defects in revision total knee arthroplasty.Methods:A retrospective analysis was conducted on 46 patients (47 knees), who underwent revision total knee arthroplasty with TM cones for metaphyseal defect reconstruction from July 2015 to August 2023. The cohort comprised 12 males and 34 females, ranging from 41 to 83 years of age, with a mean of 68.65 ± 9.09 years. Body mass index (BMI) ranged from 19.5 to 36.0 kg/m 2, averaging 27.20±4.50 kg/m 2. Bone defects were stratified according to the Anderson Orthopedic Research Institute (AORI) classification, including 64 sides (AORI T2B type 20 sides, T3 type 16 sides, F2B type 11 sides, F3 type 17 sides) which were addressed with 67 cones. Evaluations during follow-up included range of motion (ROM), visual analogue scale (VAS) for pain, and the American Knee Society Score (KSS). Long leg radiographs and knee X-rays were reassessed for femorotibial angle (FTA) and joint alignment, osseointegration of the TM cones, and any complications were documented. Results:The average follow-up duration was 46.22±26.55 months (range 16-103 months). The KSS knee score significantly improved from 29.22±19.79 preoperatively to 88.22±6.01 at the final follow-up ( F=258.118, P<0.001). Similarly, the KSS function score saw a marked increase from a preoperative average of 7.65±8.21 to 56.30±6.10 at the final follow-up ( F=354.711, P<0.001). VAS scores significantly decreased from 5.35±1.50 preoperatively to 0.28±0.50 at the final follow-up ( F=300.934, P<0.001). ROM improved from 67.72°±34.62° preoperatively to 85.33°±9.15° at the final follow-up ( F=7.798, P<0.001), and the FTA improved from 179.24°±10.30° preoperatively to 174.39°±1.69° at the final follow-up, a statistically significant enhancement ( F=9.123, P<0.001). Osseointegration was observed in 95.5% of the cases (64/67 cones). There were no instances of osteolysis or aseptic loosening observed, indicating stable prosthetic fixation. Complications were minimal, with one reported case of a femoral shaft fracture, which was successfully treated with internal fixation, resulting in satisfactory healing at 6 months. At the last follow-up (3 years after operation), the patient could walk at home with a walker and the other patients had no complications such as periprosthetic joint infection, dislocation and periprosthetic fracture. Conclusion:The application of trabecular metal cones in revision total knee arthroplasty provides an effective solution for the reconstruction of severe metaphyseal bone defects, enhancing prosthetic stability and restoring the knee joint's mechanical alignment. The trend towards successful osseointegration in the TM cones is promising, and a significant improvement in knee joint function has been observed.
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With the increasing prevalence of total knee arthroplasty (TKA), there is a corresponding rise in the number of patients requiring revision of total knee arthroplasty (R-TKA) for various reasons. R-TKA presents several complex challenges, with severe bone defect reconstruction being a critical obstacle to securing favorable long-term outcomes. Recently, the approach to managing bone defects has seen significant advancements, with a range of techniques proposed contingent on the defect's size and location. Severe bone defects require reconstruction with autologous or allogeneic bone grafts or metal fillers. However, bone grafts have their usage constrained by limited availability, risks of resorption and collapse, and the potential for disease transmission. Consequently, metal fillers have received widespread attention in practical applications due to their advantages, such as comprehensive source, customizability, and safety. The advantages of metal augment are that they provide immediate support without reinforcement and are not subject to necrosis and resorptive collapse. However, the difference in elastic modulus between metal and bone may lead to stress shielding and increase the risk of potential bone loss. Both Cone and Sleeve can achieve biological fixation of metaphyseal bone; however, in cases of periprosthetic infections, it is generally difficult to remove them easily due to the prosthetic bone in-growth and osseointegration. This study aims to provide a comprehensive review of the use of metal fillers to reconstruct bone defects during R-TKA. It is intended to aid orthopedic surgeons in understanding the spectrum of reconstructive possibilities and provide high-performance revision strategies for their patients.
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BACKGROUND:A large number of studies have confirmed that exosomes can promote osteogenesis and vascularization.However,simple exosome therapy has problems such as poor targeting,and the content of loaded molecules cannot reach the therapeutic concentration. OBJECTIVE:To load exosomes into injectable gluconolactone-sodium alginate β-tricalcium phosphate-polyethylene glycol hydrogel,and observe the effect of the hydrogel on peri-implant bone defect in vivo and in vitro. METHODS:Exosomes were extracted from bone marrow mesenchymal stem cells and wrapped in injectable gluconolactone-sodium alginate β-tricalcium phosphate-polyethylene glycol hydrogel.(1)In vitro experiment:The hydrogel loaded with exosomes and the hydrogel without exosomes were cocultured with endothelial progenitor cells,and exosomes uptake experiment,tubule formation experiment,cell proliferation,migration ability,and angiogenic gene detection were carried out.(2)In vivo experiment:Twelve male New Zealand white rabbits were used to prepare two standard implant cavities and corresponding bone defects in the long axis of one femur.A hydrogel loaded with exosomes was implanted in the bone defect after an implant was implanted in a cavity at the proximal end of the implant(experimental group),and an unloaded exosome hydrogel was implanted in the bone defect after an implant was implanted in a cavity at the distal end of the implant(control group).At 3,6 and 9 weeks after operation,bone defects with implants were removed and stained with hematoxylin-eosin staining and Masson staining.Simultaneously,osteogenic and angiogenic genes were detected at 9 weeks after operation. RESULTS AND CONCLUSION:(1)In vitro experiment:Exosomes could enter endothelial progenitor cells.The proliferation,migration,angiogenesis and gene(CD31,vascular endothelial growth factor and basic fibroblast growth factor)expression of endothelial progenitor cells in the hydrogel-loaded group were higher than those in the hydrogel-unloaded group(P<0.05).(2)In vivo experiment:Hematoxylin-eosin staining and Masson staining showed that at 3 weeks after operation,only a small amount of new bone was found in the two groups,and the material was partially degraded.At 6 weeks after operation,the amount of new bone in the two groups increased,and a large amount of new bone was found in the experimental group,with obvious calcium deposition.At 9 weeks after operation,compared with the control group,a large number of bone trabeculae thicker than mature were found in the experimental group,calcium salt deposition was more obvious,and a large number of osteoblasts were found around the bone trabeculae.The protein expressions of CD31,vascular endothelial growth factor,basic fibroblast growth factor,bone morphogenetic protein 2,type I collagen and osteocalcin in the experimental group were higher than those in the control group at 9 weeks after operation(P<0.05).(3)The exosome-loaded gluconolactone-sodium alginate β-tricalcium phosphate-polyethylene glycol hydrogel could promote the proliferation,migration and angiogenic differentiation of endothelial progenitor cells and promote the repair and regeneration of bone defects around implants.
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BACKGROUND:Metal ions play an important role in the human body.With the progress of material synthesis and processing technology,a variety of metal ions that can be used in bone tissue engineering have been developed,such as magnesium(Mg2+),zinc(Zn2+),manganese(Mn2+),strontium(Sr2+),and copper(Cu2+). OBJECTIVE:To summarize the research progress and development direction of metal ions in bone tissue engineering. METHODS:The literature collected by CNKI,PubMed and WanFang databases from 2014 to 2022 was retrieved.The Chinese and English key words were"metal ions,bone tissue engineering,osteogenic activity,magnesium ions,zinc ions,manganese ions,strontium ions,copper ions,calcium ions,lithium ions,cobalt ions". RESULTS AND CONCLUSION:Different metal ions will be released to varying degrees after the materials are implanted into the body,which can change the tissue microenvironment,thus improving the ability of materials to form blood vessels and bones.Compared with growth factors,metal ions are easier to control the release rate,have lower cost,and can also improve the mechanical properties of implant materials.The application of metal ions in bone tissue engineering is full of prospects.Although some metal ions can already be used to treat bone defects,the mechanism of action of many metal ions in the human body is not completely clear,and the application effect is a lack of clinical experiment verification.Further exploration is needed before clinical application.
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BACKGROUND:Hydrogel microparticles,due to their porous and injectable properties,have demonstrated unique advantages in biomedical fields,such as the delivery of cells and bioactive factors/drugs,the construction of tissue repair scaffolds.They have broad application prospects. OBJECTIVE:To review the latest research progress and discuss the key problems and challenges in the research of bone tissue engineering based on hydrogel microparticles. METHODS:The relevant articles in PubMed and CNKI were searched by computer.The English key words were"hydrogels,microparticles,microspheres,microcarriers,bone,bone defect,bone repair,bone healing,bone tissue engineering"while the Chinese key words were"hydrogels,microparticles,microspheres,bone tissue engineering,bone defect,bone repair,bone regeneration".The retrieval period was from 2002 to 2022,and 127 articles were finally included for review. RESULTS AND CONCLUSION:(1)At present,various hydrogel microparticles have been developed for use in bone tissue engineering strategies,for example,hydrogel microparticles carrying cells or bioactive factors/drugs,hydrogel microparticles as biological scaffolds,stimulus-responsive hydrogel microparticles,biomineralized hydrogel microparticles,hydrogel microparticles combined with other biological materials.(2)Bone tissue engineering repair strategies based on hydrogel microparticles mainly regulate bone repair by promoting stem cell recruitment and osteogenic differentiation,regulating the local inflammatory microenvironment and promoting angiogenesis at the site of injury.However,the present studies did not deeply explore the effect of bone tissue engineering based on hydrogel microparticles on the recruitment and differentiation of endogenous stem cells and the regulation of the inflammatory microenvironment by the physical and chemical properties of hydrogel microparticles.The long-term in vivo adverse reactions of hydrogel microparticles have not been explored yet,and it is difficult to mass-produce them,thus future research needs to strengthen the mechanism exploration and technical route,so as to provide a reasonable reference for the development of hydrogel microparticles that can be used for clinical transformation.
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BACKGROUND:In recent years,with the development of biological scaffold materials and bioprinting technology,tissue-engineered bone has become a research hotspot in bone defect repair. OBJECTIVE:To summarize the current treatment methods for bone defects,summarize the biomaterials and bioprinting technology for preparing tissue-engineered bone scaffolds,and explore the application of biomaterials and printing technology in tissue engineering and the current challenges. METHODS:Search terms were"bone defect,tissue engineering,biomaterials,3D printing technology,4D printing technology,bioprinting,biological scaffold,bone repair"in Chinese and English.Relevant documents published from January 1,2009 to December 1,2022 were retrieved on CNKI,PubMed and Web of Science databases.After being screened by the first author,high-quality references were added.A total of 93 articles were included for review. RESULTS AND CONCLUSION:The main treatment methods for bone defects include bone transplantation,membrane-guided regeneration,gene therapy,bone tissue engineering,etc.The best treatment method is still uncertain.Bone tissue engineering technology is a new technology for the treatment of bone defects.It has become the focus of current research by constructing three-dimensional structures that can promote the proliferation and differentiation of osteoblasts and enhance the ability of bone formation.Biological scaffold materials are diverse,with their characteristics,advantages and disadvantages.A single biological material cannot meet the demand for tissue-engineered bone for the scaffold.Usually,multiple materials are combined to complement each other,which is to meet the demand for mechanical properties while taking into account the biological properties of the scaffold.Bioprinting technology can adjust the pore of the scaffold,build a complex spatial structure,and is more conducive to cell adhesion,proliferation and differentiation.The emerging 4D printing technology introduces"time"as the fourth dimension to make the prepared scaffold dynamic.With the synchronous development of smart materials,4D printing technology provides the possibility of efficient repair of bone defects in the future.
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BACKGROUND:Early transient presence of M1 macrophages can play a beneficial role after the implantation of bone tissue engineering materials.Recently,strategies for manipulating M1 macrophages to produce an early moderate inflammatory response have been extensively studied and many research advances have been made in the design of bone tissue engineering materials. OBJECTIVE:To review the role of early transient presence of M1 macrophages in bone tissue engineering and recent research advances in the strategy for activating early transient presence of M1 macrophages in the field of bone tissue engineering. METHODS:Relevant literature included in PubMed,WanFang database,and CNKI Database from January 2012 to October 2022 was searched.Search terms were"M1,macrophage,bone immunoregulation,bone defect,osteogenesis,osteoimmunology,angiogenesis"in English and Chinese.After excluding articles irrelevant to the research purpose and repetitive articles,63 papers were finally included for review. RESULTS AND CONCLUSION:The early transient presence of M1 macrophages play a key role in bone tissue engineering by promoting angiogenesis,facilitating osteogenic differentiation of bone marrow mesenchymal stem cells and promoting an M2 macrophage phenotype.Strategies for inducing and activating early transient presence of M1 macrophages can modulate the local immune microenvironment for bone defect repair in a manner consistent with early natural bone healing,including modulation of the physicochemical properties of bone tissue engineering materials to promote appropriate M1 macrophage-mediated inflammatory responses,sequential delivery of cytokines,microRNAs or bioactive ions to facilitate the M1-to-M2 transition of macrophages,and controlled release of anti-inflammatory substances to achieve the maintenance of early inflammatory responses.
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BACKGROUND:The repair and clinical outcome of bone defects remains a hot and difficult area of clinical research,which is a common problem that plagues clinicians.Constructing suitable,reproducible and infinitely close to clinical animal experimental models and their scientific evaluation are essential for further clinical treatment of related diseases. OBJECTIVE:To retrospectively analyze the preparation methods and characteristics of common animal models of femoral bone defects and to assess their strengths and weaknesses,thereby providing some reference for relevant researchers to select appropriate animal models of femoral bone defects. METHODS:PubMed,Web of Science,Medline,and CNKI were retrieved for relevant literature published from January 1,2000 to August 1,2022.The keywords were"bone defect,bone,bones,defect,defects,defective,animal model,animal,model,laboratory,laboratory animal,animal laboratory"in English and"bone defect,animal model,experiment"in Chinese. RESULTS AND CONCLUSION:Twenty-seven randomized controlled animal experiments involving rats,mice,New Zealand rabbits,and sheep were included,analyzed and assessed.The most common types of bone defects were cylindrical bone defects and segmental osteotomy bone defects,generally found in the middle and distal femur.These models are mostly used to evaluate the effects of bone repair materials,drugs,drug-loaded active substances and physical therapy on bone defect repair and explore defect healing mechanisms,particularly the weight-bearing bone defect repair mechanism.Different defect kinds and femoral bone defect ranges have been found in different animal experiments.Researchers can select the suitable animal model and bone defect type based on the goal of the experiment and then set an acceptable bone defect value.Current studies have shown that cylindrical and segmental osteotomy-induced bone defects,mainly in the distal and middle femur,are mostly used in the animal models of femoral bone defects and that the surgical methods and postoperative management are more mature and operable to provide mature experimental animal models.In terms of cylindrical bone defects,rats and New Zealand rabbits are more suitable,whereas segmental osteotomy has no special requirements and all types of animals can meet the experimental requirements.
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BACKGROUND:Due to the complex physiological environment of the human body,a wide variety of simulated physiological fluids have been chosen for the current degradation experiments.Therefore,it is of great interest to analyze the degradation behavior of Mg-Zn-Ca alloys in different simulated body fluid environments. OBJECTIVE:To investigate the degradation process and property changes of Mg-Zn-Ca alloy in different simulated body fluids,and to clarify the influence of Ca content and simulated body fluid type on the alloy. METHODS:Mg-Zn-Ca alloys with calcium content of 0.2%,0.5%and 1%were prepared by melting extrusion molding process and were named Mg-Zn-0.2Ca,Mg-Zn-0.5Ca and Mg-Zn-1Ca alloys in turn,with Mg-Zn alloy as the control.The prepared alloys were placed into three simulated body liquids(physiological saline,PBS and Hank's solution),and the morphology,compositional changes,mass loss,pH value and mechanical properties were characterized and analyzed during the degradation. RESULTS AND CONCLUSION:(1)With the extension of degradation time,a large number of nanoscale lamellae and columnar structures were generated on the surface of the degraded alloy,and the main components were MgO and Mg(OH)2.The degradation rate of the four kinds of alloys in physiological saline was the fastest,and that in Hank's solution was the slowest.The degradation rate in physiological saline was as follows:Mg-Zn<Mg-Zn-0.2Ca<Mg-Zn-0.5Ca<Mg-Zn-1Ca.The degradation rate in PBS and Hank's solution was as follows:Mg-Zn<Mg-Zn-0.2Ca ≈ Mg-Zn-0.5Ca<Mg-Zn-1Ca.(2)With the extension of degradation time,all four kinds of alloys had a certain mass loss.The degradation in physiological saline was the fastest;the degradation in Hank's solution and PBS was slow,and in the same simulated body fluid,with the increase of calcium content in the alloy,the corrosion rate of the alloy was obviously accelerated.(3)The pH rise was mainly concentrated in 1 day and slowed down after that,and the pH change was the largest in PBS.In the same simulated body fluid,with the increase of calcium content in the alloy,the pH value in the degradation environment increased significantly.(4)In the initial state,the elastic modulus of all Mg-Zn-Ca alloys was higher than that of Mg-Zn alloys.After being placed in simulated body fluids,the elastic modulus of the four alloys decreased with the extension of degradation time,and the decrease was most obvious in physiological saline.(5)In conclusion,a small amount of Ca addition improved the mechanical properties of Mg-Zn-Ca alloy.A small amount of Ca does not accelerate the degradation rate of the alloy,but excessive Ca accelerates the degradation rate of the alloy.During the degradation,the effect of physiological saline simulated body fluid on the mechanical strength of the alloy was the most significant.
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BACKGROUND:Bone transport has been used for a variety of reasons in bone defects with good clinical results.However,various complications have also attracted the attention of practitioners and the avoidance of non-healing of the docking point has become a common concern for doctors and patients. OBJECTIVE:To explore effective methods of avoiding non-healing of the docking point in the treatment of tibial bone defects by bone transport so as to shorten the treatment period and reduce the pain of patients. METHODS:The clinical data of 21 patients with unilateral tibial bone defect admitted to the No.910 Hospital of Joint Logistics Support Force of Chinese PLA from January 2018 to January 2021 were retrospectively analyzed,including 16 males and 5 females,aged(32.8±10.3)years,with an average bone defect length of 10.2 cm.All 21 patients received bone transport surgery,during which the bone defect area was filled with bone cement to reduce the adverse factors affecting the healing of the docking point.The Association for the Study and Application of the Methods of Ilizarov,healing index and incidence of adverse reactions were evaluated during postoperative follow-up. RESULTS AND CONCLUSION:The 21 patients were followed up for 15 to 24 months after surgery,and the extended area was all well mineralized and had no malformations,and no refractures occurred during treatment.Among them,one patient had foot drop,which could not be completely corrected after surgical release of the Achilles tendon and wearing foot and ankle orthotics.19 patients had different degrees of needle tract infection,and no deep infection occurred after timely needle tract nursing.The healing rate of the docking point was 100%;the healing index was 36-45 d/cm and the average was 38 d/cm.The Association for the Study and Application of the Methods of Ilizarov showed that bone healing was excellent in 17 cases(81%)and poor in 4 cases(19%).The results of limb function were excellent in 18 cases(86%)and good in 3 cases(14%).These findings show that bone cement segmental filling during bone transport is an effective method to solve the non-healing of the docking point,shorten the patient's treatment period and reduce the patient's pain.
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BACKGROUND:In response to the limitations of traditional repair methods for bone defects,stem cells are widely used in the research of regenerative medicine.Chemical factors are the current research hotspots,but recent studies confirm that the application of physical factors to regulate stem cell differentiation at home and abroad has been intensifying,and physical factors combined with biological scaffolds in bone tissue engineering provide a new idea and method for solving the difficult problem of bone defect repair,with good development prospects. OBJECTIVE:To summarize the molecular mechanisms of physical factors such as electromagnetic fields and ultrasound on osteogenic differentiation of stem cells as well as the regulation of signaling pathways and the feasibility of their application in bone tissue engineering. METHODS:A computerized search of the CNKI and PubMed for the last 20 years was conducted.In the title and abstract,we used"stem cell,bone defect,osteogenic differentiation,electromagnetic fields,ultrasound,shock wave,low-level laser therapy,mechanical force,bone tissue engineering"in Chinese and"stem cell,osteoporosis,osteogenic differentiation,electromagnetic fields,ultrasound,bone tissue engineering"in English as search terms.A total of 94 relevant articles were included for review. RESULTS AND CONCLUSION:(1)As a non-invasive,non-contact adjuvant therapy,physical factors have a significant impact on bone tissue engineering,and have a positive effect on regulating osteogenic differentiation of stem cells,promoting cell proliferation and viability in bone engineering scaffolds.(2)In addition to activating signaling pathways and osteogenic gene transcription,physical factors can also improve vascularization,increase the volume,area and thickness of bone formed in the stent,promote osseointegration,and improve the success rate of bone scaffolds in regenerating healthy bone tissue.(3)However,the use of physical factors for bone tissue engineering uses different experimental conditions,such as scaffold type,cell type,and intervention conditions,and cannot be directly compared to determine the best parameter settings.There is also a lack of consistency in the effectiveness of these different interventions in promoting fracture healing in clinical use.Therefore,it is necessary to further determine the optimal parameters of physical factors for bone tissue engineering in the future.(4)In general,as an ideal adjuvant therapy,physical factors have great potential in combining with various biomaterials and applying them in bone tissue engineering.
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BACKGROUND:Mechanical factors can affect the angiogenic ability of vascular endothelial cells.How the vessel number affects the hydrodynamic properties of microvessels remains to be clarified. OBJECTIVE:To investigate the influence of vessel number on the hydrodynamics of vascular networks based on computational fluid dynamics. METHODS:Three three-dimensional models of vascular network with different vessel numbers were constructed using the Geometry module of ANSYS 19.0 software,and then the vascular network was meshed to tetrahedral elements in Mesh module.The vascular network was assumed to rigid wall without slip,and the blood was assumed to laminar,viscous,and incompressible Newtonian fluid.Blood density,velocity,and a series of blood viscosity coefficients were also established.The Navier-Stokes equation was used for calculation.Hydrodynamic properties of different parts of vascular network with different vessel numbers were analyzed and compared. RESULTS AND CONCLUSION:The streamline,velocity,and mass flow all had the same trend in the vascular network,that is,the outlet and inlet were higher and the middle junction of vascular network was lower.The more the number of vessels,the thinner the blood flow lines in each part of the vascular network.Also,the velocity,mass flow,and wall shear decreased with the increase of the number of blood vessels.Therefore,the changes in vessel number could influence the hydrodynamic environment in the vascular network.Computational fluid dynamics indicates that the changes in vessel numbers can influence the hydrodynamic properties of blood,and provides a new idea for treating bone hypoperfusion-induced diseases(fracture nonunion,bone defect,osteoporosis,etc.)through tonifying kidney and activating blood circulation based on the coupling between angiogenesis and osteogenesis.
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BACKGROUND:Bone defects are caused by many factors,such as inflammation,tumor,trauma or bone diseases.Erythropoietin can promote the differentiation of mesenchymal stem cells into osteoblasts and osteoclasts and act on vascular endothelial cells to induce angiogenesis and accelerate the repair of bone and cartilage defects.Erythropoietin is a growth factor with potential application in bone tissue engineering construction. OBJECTIVE:To expound the application and potential mechanism of erythropoietin in bone tissue engineering. METHODS:The first author searched the related articles published in CNKI,WanFang,VIP,and PubMed databases from 2004 to 2022 by computer.Search terms were"erythropoietin,bone defect,bone regeneration,angiogenesis,osteogenesis,osteoblast,osteoclast,bone tissue engineering"in Chinese and English.Finally,64 articles were included for review. RESULTS AND CONCLUSION:(1)Erythropoietin can directly act on osteoblasts and osteoclasts in the bone marrow microenvironment by promoting the differentiation of mesenchymal stem cells into osteoblasts,osteoclasts,adipocytes,nerve cells and stromal cells.The activation of Wnt/β-catenin,hypoxia-inducible factor 1α/vascular endothelial growth factor,p38 MAPK and EphrinB2/EphB4 signaling pathways mediates the osteogenic differentiation of mesenchymal stem cells.(2)Erythropoietin can not only regulate the production of erythrocytes to alter the oxygen-carrying capacity of blood but also stimulate vascular endothelial cells to promote angiogenesis.The new blood vessels can carry oxygen,nutrients,growth factors,and bone progenitor cells necessary for osteogenesis to the osteogenic site,thereby promoting bone formation and fracture healing.(3)Currently,erythropoietin is being used as a growth factor with osteogenic and angiogenic effects in various types of scaffold materials such as chitosan,polycaprolactone,bioceramics,and nanofibers through various drug delivery methods.Erythropoietin,along with other growth factors such as bone morphogenetic protein-2 and bone morphogenetic protein-9,has been applied to the surface of scaffold materials to participate in the repair of bone defects.Erythropoietin has demonstrated excellent practicality in the construction of new tissue-engineered bone and has potential clinical application value.
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BACKGROUND:Hydroxyapatite is the main inorganic component of bone tissue.The polymer has the structure and function of a biomimetic extracellular matrix.The composites of hydroxyapatite and polymer have been widely studied. OBJECTIVE:To summarize the research status of hydroxyapatite composite polymer materials for bone tissue repair. METHODS:The articles collected in PubMed,Web of Science,CNKI and WanFang databases were searched from January 2010 to April 2023.The Chinese and English search terms were"hydroxyapatite,polymer,composites,degradability,bone defect,bone repair".Finally,75 articles were included for review. RESULTS AND CONCLUSION:Polymers often used in composite with hydroxyapatite for bone tissue repair include natural polymers(collagen,chitosan,alginate,serine protein,cellulose,hyaluronic acid,and polyhydroxybutyrate)and synthetic polymers[polylactic acid,polylactic acid-hydroxyacetic acid copolymer,poly(has-lactide),poly(amino acid)and poly(vinyl alcohol)].The mechanical properties and osteoinductivity of hydroxyapatite/polymer composites were improved compared with pure hydroxyapatite.Hydroxyapatite composite with polymers can be made into porous scaffolds,hydrogels,and coatings for bone repair.Hydroxyapatite/polymer composites can accelerate bone reconstruction with a slow release of loaded drugs and cytokines due to their bionic extracellular matrix structure and function.Based on the diversity of causes of bone defects and the fact that bone repair is a complex continuous process involving multiple biological factors and proteins,repair materials with mechanical properties matching bone tissue,degradation processes synchronized with bone repair,and efficient osteogenesis and vascularization need to be further investigated.
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BACKGROUND:The remediation and treatment of bone defects present considerable challenges,with a variety of clinical intervention strategies available.One such approach,the Masquelet technique,has demonstrated high rates of success and reliable outcomes and is currently employed in clinical practice.However,the underlying mechanisms of this technique remain incompletely understood,and certain challenges persist in its clinical application,indicating that this technique is not yet fully mature. OBJECTIVE:To compile and categorize the biomaterials currently employed in research aimed at improving the Masquelet technique,in order to provide insights and references for the further development of this technique. METHODS:A literature search of the China National Knowledge Infrastructure and PubMed databases was conducted,spanning publications from January 2013 to November 2022.The search terms used included"Masquelet technique;induced membrane technique;induced membrane;biomaterial;bone defect"in both Chinese and English.A total of 58 articles meeting the inclusion criteria were reviewed. RESULTS AND CONCLUSION:(1)The emergence and continual development of the Masquelet technique provide a therapeutic strategy for treating bone defects.Some researchers are focusing on developing superior spacer materials,autograft substitutes,and membrane materials that mimic the properties of the induced membrane,to simplify the two-stage procedure,shorten treatment duration,and reduce patient distress.(2)Calcium sulfate,silicone,poly(lactic-co-glycolic acid),and polypropylene can replace polymethylmethacrylate bone cement to form induced membranes in animal experiments or clinical applications,each with their advantages.Contrary to expectations,common materials such as titanium and polyvinyl alcohol sponge cannot replace polymethylmethacrylate bone cement.(3)Autograft substitutes are diverse,with allograft bone,β-tricalcium phosphate,absorbable gelatin sponge,α-calcium sulfate hemihydrate,bioactive glass,titanium,and tantalum demonstrating their ability to reduce the quantity of autologous cancellous bone graft required in the second stage of the procedure.Among them,allograft bone,β-tricalcium phosphate,bioactive glass,titanium and tantalum can replace autogenous bone as grafts,and other materials need to be mixed with autogenous bone,in both clinical and fundamental experiments.(4)Biomimetic-induced membranes,human amnion,human decellularized dermis,polytetrafluoroethylene,and even autogenous cortical bone have been shown to possess properties similar to the induced membrane.(5)Most of the application and research of biomaterials in this technology still exist in the stage of basic research and have not been applied in clinical practice or popularized on a large scale,but the above materials can provide more sufficient theoretical basis and new ideas for the exploration of Masquelet technical mechanism,the improvement of surgical methods and clinical application.
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BACKGROUND:Peripheral nerves play an important role in bone metabolism.In clinical practice,the specific impact of nerve injury on bone transport technology needs further study. OBJECTIVE:To investigate the effect of tibial nerve injury on the treatment of tibial slip by single-plane osteotomy. METHODS:Thirty-two patients with tibial bone defects admitted to Tangshan Second Hospital from May 2011 to June 2022 were selected.According to the presence or absence of tibial nerve injury,patients were divided into the tibial nerve injury group(n=16)and the non-tibial nerve injury group(n=16).Both groups were treated with single-plane osteotomy and bone slip.After treatment,the patients were followed up to collect the mineralization zone healing index,external fixation index,docking point healing and needle infection.After the removal of external fixation,the bone healing and functional evaluation were evaluated by a classification of the Association for the Study and Application of the Method of Ilizarov(ASAMI). RESULTS AND CONCLUSION:(1)All 32 patients were followed up for(25.28±4.79)months.There were no significant differences in bone healing time,external fixation time,healing index and external fixation index between the two groups(P＞0.05).Needle infection occurred in two cases of the tibial nerve injury group and one case of the non-tibial nerve injury group,all of which were PALEY I,and there was no significant difference between the two groups(P＞0.05).The non-union rate of the occlusal end of the tibial nerve injury group was 31%,and that of the non-tibial nerve injury group was 13%;there was no statistical difference between the two groups(P＞0.05).The excellent and good rate of ASAMI bone healing score in the two groups was 100%;the excellent and good rate of limb score was 81%in the tibial nerve injury group and 94%in the non-tibial nerve injury group;there was no statistical difference between the two groups(P＞0.05).(2)Our research shows that tibial nerve injury has no significant effect on the mineralization speed,external fixation time,union of the occlusal end,infection of the needle tract,and the quality of bone formation in the mineralized area of the single-plane osteotomy.
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BACKGROUND:Polyvinylidene fluoride(PVDF)with piezoelectric properties,good biocompatibility and nontoxicity make it a suitable candidate for periosteal repair. OBJECTIVE:To evaluate the cytotoxicity of PVDF bionic periosteum by electrospinning with zinc and magnesium ions in vitro. METHODS:Pure PVDF,zinc-doped PVDF,magnesium-doped PVDF and Zinc-magnesium ion PVDF piezoelectric bionic periosteum were prepared by electrospinning technology,respectively.They were named PVDF,PVDF-Zn,PVDF-Mg and PVDF-Zn-Mg,in which the mass fraction of zinc and magnesium ions were all 1%.Osteoblasts and vascular endothelial cells were co-cultured with four groups of bionic periosteum.Cell compatibility of bionic periosteum was determined by alkaline phosphatase staining,CD31 immunofluorescence staining,and scanning electron microscopy. RESULTS AND CONCLUSION:(1)Osteoblasts:Alkaline phosphatase staining after 7 days of culture showed that the PVDF-Zn group secreted more alkaline phosphatase than the other three groups.Under a scanning electron microscopy,after 1 day of culture,the cells had a certain spread on the surface of PVDF-Mg and PVDF-Zn-Mg bionic periosteum,and the pseudopod extended to all sides.On day 3,the cell edge of each group extended pseudopods to the material.By days 5 and 7,the cells were fully spread,well grown and firmly covered the surface of the fibers,and the cellular pseudopods extended around and into the interstitial space of the fibers.CCK-8 assay showed that the cell proliferation on the bionic periosteum of each group showed an increasing trend over time and the relative proliferation rate of cells at 1,3,5,and 7 days was≥75%,and the cytotoxicity was≤grade 1.(2)Vascular endothelial cells:CD31 immunofluorescence staining for 3 days showed that the cells adhered and spread well on the bionic periosteum of each group and connected with each other,and the number of cells in the PVDF-Zn-Mg group was more than that in the other three groups.Under scanning electron microscope,the cells began to adhere to the surface of each group of fibers after 1 and 3 days of culture.On day 5,the cells were well spread on the surface of the fibers and extended obvious pseudopods.On day 7,the cells on the PVDF-Mg and PVDF-Zn-Mg bionic periosteum grew in multiple layers and extended the pseudopod into the fibrous void.CCK-8 assay showed that the cell proliferation on the bionic periosteum of each group showed a downward trend over time,and the relative proliferation rate of cells at 1,3,5 and 7 days was≥125%,and the cytotoxicity was grade 0.(3)The results showed that Zn-Mg electrospun PVDF piezoelectric bionic periosteum had good cytocompatibility.
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BACKGROUND:Although the clinical application of Masquelet technology has achieved extensive success,the research on optimizing all aspects of Masquelet technology is still being carried out.The focus of doctors is to speed up bone healing and shorten bone healing time after bone grafting. OBJECTIVE:To observe the effect of calcium phosphate combined with recombinant human bone morphogenetic protein-2 in repairing tibial infectious bone defects. METHODS:Thirty-one patients with tibial infectious bone defects were selected from The People's Hospital of Jianyang City from June 2017 to June 2022.They were treated with the Masquelet membrane induction technique.During the second stage of operation,they were divided into a control group(n=15)and a study group(n=16)according to different bone graft materials.Patients in the control group were implanted with autologous bone/allogeneic bone particles,and those in the study group were implanted with calcium phosphate combined with recombinant human bone morphogenetic protein-2/autologous bone particles.Six months after the second stage operation,peripheral blood inflammatory indexes such as white blood cell count,C-reactive protein,and erythrocyte sedimentation rate were detected.Imaging bone healing time,bone healing X-ray score,bone defect healing classification,and adjacent joint function were recorded.The presence of nail track infection,implant absorption,pain,and infection in the bone extraction area were observed. RESULTS AND CONCLUSION:(1)White blood cell count,erythrocyte sedimentation rate,and C-reactive protein levels of the two groups 6 months after the second stage operation were significantly lower than those before the first stage operation(P<0.05).There was no significant difference in each index between the two groups(P>0.05).(2)Bone healing time in the study group was shorter than that in the control group(P<0.05).(3)The Samantha X-ray score of the study group 6 months after the second stage operation was higher than that of the control group(P<0.05).The excellent and good rate of bone defect healing and adjacent joint function of the study group was higher than that of the control group(P<0.05).There was no significant difference in the recurrence rate and complication rate between the two groups(P>0.05).(4)These findings indicate that the effect of calcium phosphate combined with recombinant human bone morphogenetic protein-2 during the second stage operation of the Masquelet membrane induction technique in the treatment of tibial infectious bone defect is good and safe.
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BACKGROUND:Deferoxamine mesylate is a potential anti-osteoporosis drug with iron chelation,vascular regeneration,and antioxidant effects.Recent studies have shown that the application of deferoxamine mesylate can be extended to the field of tissue regeneration engineering. OBJECTIVE:To investigate whether deferoxamine mesylate can promote the repair effect of iron overload osteoporotic rats after bone grafting for mandibular bone defects by simulating the state of iron accumulation in patients with postmenopausal osteoporosis with high iron intervention in osteoporotic rats. METHODS:An iron accumulation ovariectomized osteoporosis model was firstly constructed.The model group underwent bilateral ovariectomy,and the intraperitoneal injection of ferric ammonium citrate(90 mg/kg,twice a week,for 11 weeks)was started in the 2nd week,while the sham-operated group had some fat around the ovaries removed and was given an equal amount of saline for 11 weeks.After the successful modeling,the experimental rats were divided into sham-operated group(n=6),high iron ovariectomtized group(n=6)and high iron ovariectomized deferoxamine mesylate treatment group(deferoxamine mesylate group,n=6).Bone defects of 5 mm in diameter were established in the rat's bilateral mandibles and implanted with Bio-Oss bone powder.Intraperitoneal injection of deferoxamine mesylate(100 mg/kg,3 times a week)was started on postoperative day 4 in the deferoxamine mesylate group,and equal volume of saline was given in the sham-operated and high iron ovariectomized groups.The bone samples of the mandible,liver and blood were taken at 2 and 12 weeks after bone grafting for Prussian blue staining of the jaw and liver and ELISA detection of serum ferritin to detect iron levels in various body tissues;hematoxylin-eosin staining and Masson staining were performed to observe inflammatory cell infiltration and early osteogenesis in the bone defect area;tartrate resistant acid phosphatase staining was performed to observe osteoclast differentiation;ELISA was performed to detect serum calcitonin and type I collagen C-terminal peptide levels;and Micro-CT and hematoxylin-eosin staining were performed to observe osteogenesis in the middle and late stages. RESULTS AND CONCLUSION:The number of tibial trabeculae was reduced and the trabeculae were sparsely arranged in the high iron ovariectomized group.Iron levels in the liver,jaw bone and serum were significantly higher in the high iron ovariectomized group than the sham-operated group at 2 weeks after bone grafting,while the iron levels were significantly decreased after deferoxamine mesylate intervention(P＜0.05).In the early stage of bone defect repair,more inflammatory cell infiltration,less new bone matrix and less type I collagen fiber production were observed in the high iron ovariectomized group than in the sham-operated group(P＜0.05);after deferoxamine mesylate treatment,inflammatory cell infiltration was reduced,a small amount of new bone matrix was produced and collagen fibers increased significantly(P＜0.05).In the middle and late stages of bone defect repair,Micro-CT results showed a reduction in new bone production in the high iron ovariectomized group compared with the sham-operated group and increased new bone matrix after deferoxamine mesylate treatment(P＜0.05).Compared with the sham-operated group,the osteoclast number,serum calcitonin level,and serum type I collagen C-terminal peptide level were increased in the high-iron ovariectomized group,while the osteoclast number was decreased and bone metabolic indexes were improved after treatment with deferoxamine mesylate.To conclude,in ovariectomized rats with high iron intervention,elevated iron levels can be seen in multiple tissues,accompanied by reduced new bone production in the mandibular bone defect area.Deferoxamine mesylate can improve bone metabolism and inhibit osteoclast activity by removing iron deposits in tissues,improve bone formation in iron-accumulated osteoporotic rats,and promote bone healing in the mandibular bone defect area.