The original online version of this article was revised:The layout update for Article 758 has impacted the page range in the published issue,but did not affect the scholarly content.To ensure consistency with the orig...The original online version of this article was revised:The layout update for Article 758 has impacted the page range in the published issue,but did not affect the scholarly content.To ensure consistency with the originally assigned pages(2595-2614),we will need to publish an erratum to correct the article and restore the original page range.The original article has been corrected.展开更多
Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue en...Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue engineering scaffolds is of great significance for bone repair.This study synthesized copper(Cu)-doped mesoporous silica nanoparticles(Cu@MSN)modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN(Cu@MSNMA).Furtheremore,bio-mimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution.This hydrogel achieves multi-modal bone tissue biomimicry:(ⅰ)GelMA/gelatin mimics the matrix components in bone ECM,ensuring biocompatibility while promoting cellular behavior(such as adhesion,proliferation,and differentiation);(ⅱ)GelMA/gela-tin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure,achieving structural and mechanical biomimicry to provide necessary support for bone defects;(ⅲ)The elemental biomimicry of Si and Cu in Cu@MSNMA achieves efficient osteogenic induction.The effect of different proportions of Cu@MSNMA on the physi-cal properties of the composite hydrogels was investigated to determine the optimal proportion.The results indicated that the mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio.Notably,5%NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel.In vitro and vivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition.In conclusion,the proposed nanocomposite hydrogel with biomimetic components and ion-regulating properties can serve as a multifunctional scaffold,offering antimicrobial properties for infected bone regeneration,and guide for future research in bone regeneration and three-dimensional printing.展开更多
Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal t...Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal therapy hydrogel with a pulsed drug delivery mechanism.The system is predicated on a hydrogel matrix that is thermally responsive,characteristic of bone defect sites,facilitating controlled and site-specific drug release.The cornerstone of this system is the incorporation of mild photothermal nanoparticles,which are activated within the temperature range of 40–43°C,thereby enhancing the precision and efficacy of drug delivery.Our findings demonstrate that the photothermal response significantly augments the localized delivery of therapeutic agents,mitigating systemic side effects and bolstering efficacy at the defect site.The synchronized pulsed release,cooperated with mild photothermal therapy,effectively addresses infection control,and promotes bone regeneration.This approach signifies a considerable advancement in the management of infectious bone defects,offering an effective and patient-centric alternative to traditional methods.Our research endeavors to extend its applicability to a wider spectrum of tissue regeneration scenarios,underscoring its transformative potential in the realm of regenerative medicine.展开更多
As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially ...As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially in the context of an imbalance between osteoblast and osteoclast activities.Therefore,the development of new biomaterials has become the key.This article reviews various design strategies and their advantages and disadvantages for biomaterials aimed at osteoporotic bone defects.Overall,current research progress indicates that innovative design,functionalization,and targeting of materials can significantly enhance bone regeneration under osteoporotic conditions.By comprehensively considering biocompatibility,mechanical properties,and bioactivity,these biomaterials can be further optimized,offering a range of choices and strategies for the repair of osteoporotic bone defects.展开更多
BACKGROUND The induced-membrane technique was initially described by Masquelet as an effective treatment for large bone defects,especially those caused by infection.Here,we report a case of chronic osteomyelitis of th...BACKGROUND The induced-membrane technique was initially described by Masquelet as an effective treatment for large bone defects,especially those caused by infection.Here,we report a case of chronic osteomyelitis of the radius associated with a 9 cm bone defect,which was filled with a large allogeneic cortical bone graft from a bone bank.Complete bony union was achieved after 14 months of follow-up.Previous studies have used autogenous bone as the primary bone source for the Masquelet technique;in our case,the exclusive use of allografts is as successful as the use of autologous bone grafts.With the advent of bone banks,it is possible to obtain an unlimited amount of allograft,and the Masquelet technique may be further improved based on this new way of bone grafting.CASE SUMMARY In this study,we reported a case of repair of a long bone defect in a 40-year-old male patient,which was characterized by the utilization of allograft cortical bone combined with the Masquelet technique for the treatment of the patient's long bone defect in the forearm.The patient's results of functional recovery of the forearm were surprising,which further deepens the scope of application of Masquelet technique and helps to strengthen the efficacy of Masquelet technique in the treatment of long bones indeed.CONCLUSION Allograft cortical bone combined with the Masquelet technique provides a new method of treatment to large bone defect.展开更多
Large bone defects in load-bearing bone can result from tumor resection,osteomyelitis,trauma,and other factors.Although bone has the intrinsic potential to self-repair and regenerate,the repair of large bone defects w...Large bone defects in load-bearing bone can result from tumor resection,osteomyelitis,trauma,and other factors.Although bone has the intrinsic potential to self-repair and regenerate,the repair of large bone defects which exceed a certain critical size remains a substantial clinical challenge.Traditionally,repair methods involve using autologous or allogeneic bone tissue to replace the lost bone tissue at defect sites,and autogenous bone grafting remains the“gold standard”treatment.However,the application of traditional bone grafts is limited by drawbacks such as the quantity of extractable bone,donor-site morbidities,and the risk of rejection.In recent years,the clinical demand for alternatives to traditional bone grafts has promoted the development of novel bone-grafting substitutes.In addition to osteoconductivity and osteoinductivity,optimal mechanical properties have recently been the focus of efforts to improve the treatment success of novel bone-grafting alternatives in load-bearing bone defects,but most biomaterial synthetic scaffolds cannot provide sufficient mechanical strength.A fundamental challenge is to find an appropriate balance between mechanical and tissue-regeneration requirements.In this review,the use of traditional bone grafts in load-bearing bone defects,as well as their advantages and disadvantages,is summarized and reviewed.Furthermore,we highlight recent development strategies for novel bone grafts appropriate for load-bearing bone defects based on substance,structural,and functional bionics to provide ideas and directions for future research.展开更多
The regeneration of infected bone defects is still challenging and time-consuming,due to the adverse osteogenic microenvironment caused by bacterial contamination and pronounced ischemia.Biodegradable magnesium(Mg)-ba...The regeneration of infected bone defects is still challenging and time-consuming,due to the adverse osteogenic microenvironment caused by bacterial contamination and pronounced ischemia.Biodegradable magnesium(Mg)-based alloys are desirable for orthopedic implants due to the mechanical properties approximating those of human bone and the released Mg^(2+)ions essential to osteogenic activity.However,the fast and uncontrolled self-degradation of Mg alloy,along with the inadequate antimicrobial activity,limit their strength in the osteogenic microenvironment.Inspired by the structural and physiological characteristics of“fish scales,”two-dimensional(2D)nanomaterials,black phosphorus(BP)and graphene oxide(GO),were assembled together under the action of pulsed electric field.The bionic 2D layered BP/GO nano-coating was constructed for infection resistance,osteogenic microenvironment optimization,and biodegradation control.In the early stage of implantation,it exerted a photothermal effect to ablate bacterial biofilms and avoid contaminating the microenvironment.The blocking effect of the“nano fish scales”-2D material superposition regulated the degradation of implants.In the later stage,it attracted the migration of vascular endothelial cells(VECs)and released phosphate slowly for in situ mineralization to create the microenvironment favoring vascularized bone formation.It is indicated that the enhancement of microtubule deacetylation and cytoskeletal reorganization played a key role in the effect of VEC migration and angiogenesis.This study provided a promising bionic strategy for creating osteogenic microenvironments that match the sequential healing process of infected bone defects.展开更多
The technology of three dimensional(3D) printing,also known as additive manufacturing,is a cuttingedge type of fabrication method that utilizes a computer-aided design platform and employs layer-bylayer stacking to co...The technology of three dimensional(3D) printing,also known as additive manufacturing,is a cuttingedge type of fabrication method that utilizes a computer-aided design platform and employs layer-bylayer stacking to construct objects with exceptional flexibility.Due to its capacity to produce a substantial quantity of products within a short period of time,3D printing has emerged as one of the most significant manufacturing technology.Over the past two decades,remarkable advancements have been made in the application of 3D printing technology in the realm of bone tissue engineering.This review presents an innovative and systematic discussion on the potential application of 3D printing technology in bone tissue engineering,particularly in the treatment of infected bone defects.It comprehensively evaluates the materials utilized in 3D printing,highlights the interplay between cells and bone regeneration,and addresses and resolves challenges associated with current 3D printing technology.These challenges include material selection,fabrication of intricate 3D structures,integration of different cell types,streamlining design processes and material selection procedures,enhancing the clinical translational potential of 3D printing technology,and ultimately exploring future applications of four dimensional(4D) printing technology.The 3D printing technology has demonstrated significant potential in the synthesis of bone substitutes,offering consistent mechanical properties and ease of use.It has found extensive applications in personalized implant customization,prosthetic limb manufacturing,surgical tool production,tissue engineering,biological modeling,and cell diagnostics.Simultaneously,3D bioprinting provides an effective solution to address the issue of organ donor shortage.However,challenges still exist in material selection,management of structural complexity,integration of different cell types,and construction of functionally mature tissues.With advancements in multi-material printing techniques as well as bioprinting and 4D printing technologies emerging on the horizon;3D printing holds immense prospects for revolutionizing the means by which infectious bone defects are repaired.展开更多
Bone defects represent a significant clinical challenge with diverse etiologies,including but not limited to tumors,trauma,necrosis,and congenital deformities,imposing substantial patient suffering and socioeconomic b...Bone defects represent a significant clinical challenge with diverse etiologies,including but not limited to tumors,trauma,necrosis,and congenital deformities,imposing substantial patient suffering and socioeconomic burdens.In recent years,novel approaches for bone defect repair have been continuously explored.Biodegradable synthetic materials,particularly those capable of gradual decomposition during tissue regeneration processes,are recognized as ideal candidates for bone repair implants.Natural or synthetic polymer-based materials have been extensively employed in osteochondral repair due to their favorable biocompatibility.Furthermore,biodegradable magnesium(Mg)-based metals constitute another crucial category of bone substitutes.Mg alloys demonstrate unique advantages,including tunable degradation rates,excellent biocompatibility,appropriate mechanical strength,and remarkable osteogenic potential,positioning Mgcontaining implants as a pivotal direction in bone regenerative medicine.However,clinical applications of Mg alloys still face challenges such as rapid degradation kinetics and insufficient osteogenic performance.Further investigation into advanced application strategies for Mg alloys holds significant clinical implications for bone defect therapeutics.展开更多
Management of post-traumatic long-bone defects remains relevant and cha-llenging despite the rapid development of approaches to their treatment.Do-minant positions are occupied by the Ilizarov method,bone autogenous g...Management of post-traumatic long-bone defects remains relevant and cha-llenging despite the rapid development of approaches to their treatment.Do-minant positions are occupied by the Ilizarov method,bone autogenous grafting and the Masquelet induced membrane technique(IMT).The IMT is aimed at reducing extensive defect treatment duration and for this reason has gained great popularity.However,the assessment of its effectiveness is difficult due to a limited number of clinical series.The varying clinical manifestations of bone defect severity do not allow a comprehensive evaluation of IMT effectiveness.One of them is infection in the defect area.The purpose of our literature review is an analysis of studies on IMT application in infected vs non-infected long-bone defects of the lower extremities published over the last 10 years.It focuses on the investigation of similarities and fundamental differences in the need for antibiotics,timing of spacer fixation,methods of collecting donor bone and fixators used for consolidation.The studies show that the IMT has been globally used in aseptic and osteomyelitic defects due to its clinical effectiveness.Authors’variations and improvements in its practical implementation indicate the ongoing development and the interest of researchers in this technique.展开更多
Recent advances in bone regeneration have introduced the concept of four-dimensional(4D)scaffolds that can undergo morphological and functional changes in response to external stimuli.While several studies have propos...Recent advances in bone regeneration have introduced the concept of four-dimensional(4D)scaffolds that can undergo morphological and functional changes in response to external stimuli.While several studies have proposed patient-specific designs for defect sites,they often fail to adequately distinguish the advantages of 4D scaffolds over conventional 3D counterparts.This study aimed to investigate the potential benefits of 4D scaffolds in clinically challenging scenarios involving curved defects,where fixation is difficult.We proposed the use of Shape-Memory Polymers(SMPs)as a solution to address critical issues in personalized scaffold fabrication,including dimensional accuracy,measurement error,and manufacturing imprecision.Experimental results demonstrated that the Curved-Layer Fused Deposition Modeling(CLFDM)scaffold,which offers superior conformability to curved defects,achieved significantly higher interfacial contact with the defect area compared to traditional Fused Deposition Modeling(FDM)scaffolds.Specifically,the CLFDM scaffold facilitated bone regeneration of 25.59±4.72 mm^(3),which is more than twice the 9.37±1.36 mm^(3)observed with the 3D FDM scaffold.Furthermore,the 4D CLFDM scaffold achieved 75.38±11.65 mm^(3)of new bone formation after four weeks,approximately three times greater than that of the 3D CLFDM scaffold,regardless of surface micro-roughness.These results underscore that improved geometrical conformity between the scaffold and the defect site enhances cellular infiltration and contributes to more effective bone regeneration.The findings also highlight the promise of 4D scaffolds as a compelling strategy to overcome geometric and dimensional mismatches in the design of patient-specific scaffolds.展开更多
This study aimed to utilize micro-computed tomography （micro-CT） analysis to compare new bone formation in rat calvarial defects using chitosan/fibroin-hydroxyapatite （CFB-HAP） or collagen （Bio-Gide） membranes. ...This study aimed to utilize micro-computed tomography （micro-CT） analysis to compare new bone formation in rat calvarial defects using chitosan/fibroin-hydroxyapatite （CFB-HAP） or collagen （Bio-Gide） membranes. Fifty-four （54） rats were studied. A circular bony defect （8 mm diameter） was formed in the centre of the calvaria using a trephine bur. The CFB-HAP membrane was prepared by thermally induced phase separation. In the experimental group （n= 18）, the CFB-HAP membrane was used to cover the bony defect, and in the control group （n= 18）, a resorbable collagen membrane （Bio-Gide） was used. In the negative control group （n= 18）, no membrane was used. In each group, six animals were euthanized at 2, 4 and 8 weeks after surgery. The specimens were then analysed using micro-CT. There were significant differences in bone volume （BV） and bone mineral density （BMD） （P〈O.05） between the negative control group and the membrane groups. However, there were no significant differences between the CFB-HAP group and the collagen group. We concluded that the CFB-HAP membrane has significant potential as a guided bone regeneration （GBR） membrane.展开更多
We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve de...We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects.To test this,we established rabbit models of 30 mm sciatic nerve defects,and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells.We compared the tensile properties,electrophysiological function and morphology of the damaged nerve in each group.Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone,and produced similar results to those observed with the autograft.These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects.展开更多
BACKGROUND Ilizarov non-free bone plasty is a method of distraction osteogenesis using the Ilizarov apparatus for external fixation which originated in Russia and was disseminated across the world. It has been used in...BACKGROUND Ilizarov non-free bone plasty is a method of distraction osteogenesis using the Ilizarov apparatus for external fixation which originated in Russia and was disseminated across the world. It has been used in long bone defect and nonunion management along with free vascularized grafting and induced membrane technique. However, the shortcomings and problems of these methods still remain the issues which restrict their overall use.AIM To study the recent available literature on the role of Ilizarov non-free bone plasty in long bone defect and nonunion management, its problems and the solutions to these problems in order to achieve better treatment outcomes.METHODS Three databases(Pub Med, Scopus, and Web of Science) were searched for literature sources on distraction osteogenesis, free vascularized grafting and induced membrane technique used in long bone defect and nonunion treatment within a five-year period(2015-2019). Full-text clinical articles in the English language were selected for analysis only if they contained treatment results,complications and described large patient samples(not less than ten cases for congenital, post-tumor resection cases or rare conditions, and more than 20 cases for the rest). Case reports were excluded.RESULTS Fifty full-text articles and reviews on distraction osteogenesis were chosen.Thirty-five clinical studies containing large series of patients treated with this method and problems with its outcome were analyzed. It was found that distraction osteogenesis techniques provide treatment for segmental bone defects and nonunion of the lower extremity in many clinical situations, especially in complex problems. The Ilizarov techniques treat the triad of problems simultaneously(bone loss, soft-tissue loss and infection). Management of tibial defects mostly utilizes the Ilizarov circular fixator. Monolateral fixators are preferable in the femur. The use of a ring fixator is recommended in patients with an infected tibial bone gap of more than 6 cm. High rates of successful treatment were reported by the authors that ranged from 77% to 100% and depended on the pathology and the type of Ilizarov technique used. Hybrid fixation and autogenous grafting are the most applicable solutions to avoid after-frame regenerate fracture or deformity and docking site nonunion.CONCLUSION The role of Ilizarov non-free bone plasty has not lost its significance in the treatment of segmental bone defects despite the shortcomings and treatment problems encountered.展开更多
The aim of the present real time in vivo micro-computed tomography （pCT） and histologic experiment was to assess the efficacy of guided bone regeneration （GBR） around standardized calvarial critical size defects ...The aim of the present real time in vivo micro-computed tomography （pCT） and histologic experiment was to assess the efficacy of guided bone regeneration （GBR） around standardized calvarial critical size defects （CSD） using bone marrow-derived mesenchymal stem cells （BMSCs）, and collagen membrane （CM） with and without tricalcium phosphate （TCP） graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD （diameter 4.6 mm） were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone （NFB） and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo pCT. At the lOth week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups I and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical ＂lock＂ between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adiunct BMSC therapy.展开更多
Summary： This study evaluated the clinical effect of impaction bone graft and distal press-fit fixation for the reconstruction of severe femoral bone defect in revision total hip arthroplasty. A total of 234 patients...Summary： This study evaluated the clinical effect of impaction bone graft and distal press-fit fixation for the reconstruction of severe femoral bone defect in revision total hip arthroplasty. A total of 234 patients （involving 236 hips） with Paprosky III and 1V femoral bone defects were treated with the revision total hip arthroplasty from June 1998 to Aug. 2006. Impaction bone graft technique was used for 112 hips, with allogeneic freeze-dried bone as bone graft and SP II as prosthesis. With 124 hips, modular distal press-fit fixation and tapered femoral stem （MP stem） were employed. After the operation, the subjects were followed up on regular basis and results were assessed by using the Harris Hip Score （HHS） and 12-item Short Form Health Survey （SF-12）. Radiolucence, subsidence and loosening were observed and complications, including infection, fracture, dislocation etc. were recorded. A 6-14-year follow-up showed that prostheses failed, due to infection, in 4 patients of impaction bone graft group and that 6 patients in the press-fit fixation group experienced prosthesis failure, with the survival rates for the two techniques being 96.43% and 95.16%, respectively. One-way ANOVA showed that prosthesis survival was significantly associated with surgery-related complications （P〈0.05） and was not related to the type of the bone defects （P〉0.05）. The rate of complications bore significant association with the type of bone defects in the two groups （P〈0.05）. Our study showed that the two revision methods could achieve satisfactory mid-term and long-term results for the reconstruction of severe bone defects. It is of great significance for attaining high prosthesis survival rate to select suitable operation on the basis of the type of bone defect. Careful operative manipulation and post-operative rehabilitation aimed at reducing complications are also important.展开更多
Objective：To study the possibility of natural hydroxyapatite/chitosan composite on repairing bone defects. Methods：We developed a natural hydroxyapatite/chitosan composite that could be molded into any desired shape...Objective：To study the possibility of natural hydroxyapatite/chitosan composite on repairing bone defects. Methods：We developed a natural hydroxyapatite/chitosan composite that could be molded into any desired shape. The powder component consists of natural hydroxyapatite, which is epurated from bone of pigs. The liquid component consists of malic acid and chitosan. Operations were performed on the left tibias of 15 white rabbits to create two square bone defects. One of the defects was reconstructed with the composite, while the other was not repaired and used as a blank control. Three of the animals were killed at the end of 2 weeks, 4 weeks, 8 weeks, 12 weeks and 16 weeks respectively and implants were evaluated anatomically and histologically. Results：No apparent rejection reaction was found, except for a mild inflammatory infiltration observed 2 weeks after surgery. Fibrous tissue became thinner 2 -8 weeks after surgery and bony connections were detected 12 weeks after surgery. The new bone was the same as the recipient bone by the 16th postoperative week. Conclusion：The hydroxyapatite/chitosan composite has good biocompatibility and osteoconduction. It is a potential repairing material for clinical application.展开更多
BACKGROUND Critically sized bone defects represent a significant challenge to orthopaedic surgeons worldwide.These defects generally result from severe trauma or resection of a whole large tumour.Autologous bone graft...BACKGROUND Critically sized bone defects represent a significant challenge to orthopaedic surgeons worldwide.These defects generally result from severe trauma or resection of a whole large tumour.Autologous bone grafts are the current gold standard for the reconstruction of such defects.However,due to increased patient morbidity and the need for a second operative site,other lines of treatment should be introduced.To find alternative unconventional therapies to manage such defects,bone tissue engineering using a combination of suitable bioactive factors,cells,and biocompatible scaffolds offers a promising new approach for bone regeneration.AIM To evaluate the healing capacity of platelet-rich fibrin(PRF)membranes seeded with allogeneic mesenchymal bone marrow-derived stem cells(BMSCs)on critically sized mandibular defects in a rat model.METHODS Sixty-three Sprague Dawley rats were subjected to bilateral bone defects of critical size in the mandibles created by a 5-mm diameter trephine bur.Rats were allocated to three equal groups of 21 rats each.Group I bone defects were irrigated with normal saline and designed as negative controls.Defects of group II were grafted with PRF membranes and served as positive controls,while defects of group III were grafted with PRF membranes seeded with allogeneic BMSCs.Seven rats from each group were killed at 1,2 and 4 wk.The mandibles were dissected and prepared for routine haematoxylin and eosin(HE)staining,Masson's trichrome staining and CD68 immunohistochemical staining.RESULTS Four weeks postoperatively,the percentage area of newly formed bone was significantly higher in group III(0.88±0.02)than in groups I(0.02±0.00)and II(0.60±0.02).The amount of granulation tissue formation was lower in group III(0.12±0.02)than in groups I(0.20±0.02)and II(0.40±0.02).The number of inflammatory cells was lower in group III(0.29±0.03)than in groups I(4.82±0.08)and II(3.09±0.07).CONCLUSION Bone regenerative quality of critically sized mandibular bone defects in rats was better promoted by PRF membranes seeded with BMSCs than with PRF membranes alone.展开更多
TGF-β is a multifunctional cytokine that regulates many aspects of cellular function, including periosteal mesenchymal cell proliferation, differentiation. This experiment is to study its effects on bone defect repai...TGF-β is a multifunctional cytokine that regulates many aspects of cellular function, including periosteal mesenchymal cell proliferation, differentiation. This experiment is to study its effects on bone defect repair. A rabbit radial bone defect model was used to evaluate the effect of TGF-β, which was extracted and purified from bovine blood platelets, on the healing of a large segmental osteoperiosteal defect. A 1. 5-centimeter segmental defect was created in the mid-upper part of the radial shaft of adult rabbits. The defect was filled with implant containing TGF-β that consisted of carrier and bovine TGF-β. Limbs served as controls received carrier alone. The defectswere examined radiographically and histologically at 4, 8,12 , 16 and 20 weeks after implantation. The results showed that in TGF-β implant group . the defect areas at 12 weeks post operation were bridged by uniform new bone and the cut ends of cortex could not be seen;while in control group, the defects remained clear. Only a small amount of new bone formed as a cap on the cut bone ends. In the experimental group, new lamellar and woven bone formed in continuity with the cut ends of the cortex. An early medullar canal appears to be forming and contained normal-appearancing marrow elements; while the control group displayed entirely fibrous tissue within the defect site. Remnants of the cancellous bone carrier were observed in the control specimen. These data demonstrate that exogenous TGF-β initiate osteogenesis and stimulate the bone defects repair in animal model.展开更多
Periosteum is a thin membrane that encases the surfaces of most bones.It is composed of an outer fibrous layer contains longitudinally oriented cells and collagen fibers and an inner cambial layer that consists of mul...Periosteum is a thin membrane that encases the surfaces of most bones.It is composed of an outer fibrous layer contains longitudinally oriented cells and collagen fibers and an inner cambial layer that consists of multipotent mesenchymal stem cells（MSCs）and osteogenic progenitor cells.Periosteum has a function of regulating cell and collagen arrangement,which is important to the integrity,modelling and remodelling of bone,particularly during bone defect repair.Apart from autograft and allograft,artificial periosteum,or tissue-engineered periosteum mimicking native periosteum in structure or function,made up of small intestinal submucosa,acellular dermis,induced membrane,cell sheets,and polymeric scaffolds,and so on,has been developed to be used in bone defect repair.In this review,we classify the artificial periosteum into three approaches based on the material source,that is,native tissues,scaffoldfree cell sheets and scaffold-cell composites.Mechanisms,methods and efficacy of each approach are provided.Existing obstacles and enabling technologies for future directions are also discussed.展开更多
文摘The original online version of this article was revised:The layout update for Article 758 has impacted the page range in the published issue,but did not affect the scholarly content.To ensure consistency with the originally assigned pages(2595-2614),we will need to publish an erratum to correct the article and restore the original page range.The original article has been corrected.
基金National Key R&D Program of China(grant number 2022YFA1207500)National Natural Science Foundation of China(grant number 82072412).
文摘Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue engineering scaffolds is of great significance for bone repair.This study synthesized copper(Cu)-doped mesoporous silica nanoparticles(Cu@MSN)modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN(Cu@MSNMA).Furtheremore,bio-mimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution.This hydrogel achieves multi-modal bone tissue biomimicry:(ⅰ)GelMA/gelatin mimics the matrix components in bone ECM,ensuring biocompatibility while promoting cellular behavior(such as adhesion,proliferation,and differentiation);(ⅱ)GelMA/gela-tin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure,achieving structural and mechanical biomimicry to provide necessary support for bone defects;(ⅲ)The elemental biomimicry of Si and Cu in Cu@MSNMA achieves efficient osteogenic induction.The effect of different proportions of Cu@MSNMA on the physi-cal properties of the composite hydrogels was investigated to determine the optimal proportion.The results indicated that the mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio.Notably,5%NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel.In vitro and vivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition.In conclusion,the proposed nanocomposite hydrogel with biomimetic components and ion-regulating properties can serve as a multifunctional scaffold,offering antimicrobial properties for infected bone regeneration,and guide for future research in bone regeneration and three-dimensional printing.
基金supported by the National Natural Science Foundation of China(32171354,82222015,82171001)The National Key Research and Development Program of China2023YFC2413600Research Funding from West China School/Hospital of Stomatology,Sichuan University(No.RCDWIS2023-1).
文摘Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal therapy hydrogel with a pulsed drug delivery mechanism.The system is predicated on a hydrogel matrix that is thermally responsive,characteristic of bone defect sites,facilitating controlled and site-specific drug release.The cornerstone of this system is the incorporation of mild photothermal nanoparticles,which are activated within the temperature range of 40–43°C,thereby enhancing the precision and efficacy of drug delivery.Our findings demonstrate that the photothermal response significantly augments the localized delivery of therapeutic agents,mitigating systemic side effects and bolstering efficacy at the defect site.The synchronized pulsed release,cooperated with mild photothermal therapy,effectively addresses infection control,and promotes bone regeneration.This approach signifies a considerable advancement in the management of infectious bone defects,offering an effective and patient-centric alternative to traditional methods.Our research endeavors to extend its applicability to a wider spectrum of tissue regeneration scenarios,underscoring its transformative potential in the realm of regenerative medicine.
基金supported by the National Natural Science Foundation of China(Nos.82160419 and 82302772)Guizhou Basic Research Project(No.ZK[2023]General 201)。
文摘As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially in the context of an imbalance between osteoblast and osteoclast activities.Therefore,the development of new biomaterials has become the key.This article reviews various design strategies and their advantages and disadvantages for biomaterials aimed at osteoporotic bone defects.Overall,current research progress indicates that innovative design,functionalization,and targeting of materials can significantly enhance bone regeneration under osteoporotic conditions.By comprehensively considering biocompatibility,mechanical properties,and bioactivity,these biomaterials can be further optimized,offering a range of choices and strategies for the repair of osteoporotic bone defects.
文摘BACKGROUND The induced-membrane technique was initially described by Masquelet as an effective treatment for large bone defects,especially those caused by infection.Here,we report a case of chronic osteomyelitis of the radius associated with a 9 cm bone defect,which was filled with a large allogeneic cortical bone graft from a bone bank.Complete bony union was achieved after 14 months of follow-up.Previous studies have used autogenous bone as the primary bone source for the Masquelet technique;in our case,the exclusive use of allografts is as successful as the use of autologous bone grafts.With the advent of bone banks,it is possible to obtain an unlimited amount of allograft,and the Masquelet technique may be further improved based on this new way of bone grafting.CASE SUMMARY In this study,we reported a case of repair of a long bone defect in a 40-year-old male patient,which was characterized by the utilization of allograft cortical bone combined with the Masquelet technique for the treatment of the patient's long bone defect in the forearm.The patient's results of functional recovery of the forearm were surprising,which further deepens the scope of application of Masquelet technique and helps to strengthen the efficacy of Masquelet technique in the treatment of long bones indeed.CONCLUSION Allograft cortical bone combined with the Masquelet technique provides a new method of treatment to large bone defect.
基金supported by the National Natural Science Foundation of China(No.82202450).
文摘Large bone defects in load-bearing bone can result from tumor resection,osteomyelitis,trauma,and other factors.Although bone has the intrinsic potential to self-repair and regenerate,the repair of large bone defects which exceed a certain critical size remains a substantial clinical challenge.Traditionally,repair methods involve using autologous or allogeneic bone tissue to replace the lost bone tissue at defect sites,and autogenous bone grafting remains the“gold standard”treatment.However,the application of traditional bone grafts is limited by drawbacks such as the quantity of extractable bone,donor-site morbidities,and the risk of rejection.In recent years,the clinical demand for alternatives to traditional bone grafts has promoted the development of novel bone-grafting substitutes.In addition to osteoconductivity and osteoinductivity,optimal mechanical properties have recently been the focus of efforts to improve the treatment success of novel bone-grafting alternatives in load-bearing bone defects,but most biomaterial synthetic scaffolds cannot provide sufficient mechanical strength.A fundamental challenge is to find an appropriate balance between mechanical and tissue-regeneration requirements.In this review,the use of traditional bone grafts in load-bearing bone defects,as well as their advantages and disadvantages,is summarized and reviewed.Furthermore,we highlight recent development strategies for novel bone grafts appropriate for load-bearing bone defects based on substance,structural,and functional bionics to provide ideas and directions for future research.
基金supported by the National Natural Science Foundation of China[81801007]the Traditional Chinese Medicine Bureau of Guangdong Province[20242062]+2 种基金the Major of Basic and Applied Basic Research Project of Guangzhou City[202201011601]the Science and Cultivation Foundation of Stomatological Hospital of Southern Medical University[PY2021016]the Guangdong Province Clinical Teaching Base Teaching Reform Research Project[2023JD054].
文摘The regeneration of infected bone defects is still challenging and time-consuming,due to the adverse osteogenic microenvironment caused by bacterial contamination and pronounced ischemia.Biodegradable magnesium(Mg)-based alloys are desirable for orthopedic implants due to the mechanical properties approximating those of human bone and the released Mg^(2+)ions essential to osteogenic activity.However,the fast and uncontrolled self-degradation of Mg alloy,along with the inadequate antimicrobial activity,limit their strength in the osteogenic microenvironment.Inspired by the structural and physiological characteristics of“fish scales,”two-dimensional(2D)nanomaterials,black phosphorus(BP)and graphene oxide(GO),were assembled together under the action of pulsed electric field.The bionic 2D layered BP/GO nano-coating was constructed for infection resistance,osteogenic microenvironment optimization,and biodegradation control.In the early stage of implantation,it exerted a photothermal effect to ablate bacterial biofilms and avoid contaminating the microenvironment.The blocking effect of the“nano fish scales”-2D material superposition regulated the degradation of implants.In the later stage,it attracted the migration of vascular endothelial cells(VECs)and released phosphate slowly for in situ mineralization to create the microenvironment favoring vascularized bone formation.It is indicated that the enhancement of microtubule deacetylation and cytoskeletal reorganization played a key role in the effect of VEC migration and angiogenesis.This study provided a promising bionic strategy for creating osteogenic microenvironments that match the sequential healing process of infected bone defects.
基金supported by the National Natural Science Fund of China(Nos.82202726,82370929)the National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University(No.Z20192013)+5 种基金Key research and development project of Sichuan Science and Technology Department(No.2023YFG0219)"Zeroto One" Innovation Research Project of Sichuan University(No.2022SCUH0014)Frontiers Medical Center,Tianfu Jincheng Laboratory Foundation(No.TFJC2023010001)Sichuan Science and Technology Program(No.2022NSFSC0002)Sichuan Province Youth Science and Technology Innovation Team(No.2022JDTD0021)Research and Develop Program,West China Hospital of Stomatology Sichuan University(Nos.RD03202302,RCDWJS2024-1)。
文摘The technology of three dimensional(3D) printing,also known as additive manufacturing,is a cuttingedge type of fabrication method that utilizes a computer-aided design platform and employs layer-bylayer stacking to construct objects with exceptional flexibility.Due to its capacity to produce a substantial quantity of products within a short period of time,3D printing has emerged as one of the most significant manufacturing technology.Over the past two decades,remarkable advancements have been made in the application of 3D printing technology in the realm of bone tissue engineering.This review presents an innovative and systematic discussion on the potential application of 3D printing technology in bone tissue engineering,particularly in the treatment of infected bone defects.It comprehensively evaluates the materials utilized in 3D printing,highlights the interplay between cells and bone regeneration,and addresses and resolves challenges associated with current 3D printing technology.These challenges include material selection,fabrication of intricate 3D structures,integration of different cell types,streamlining design processes and material selection procedures,enhancing the clinical translational potential of 3D printing technology,and ultimately exploring future applications of four dimensional(4D) printing technology.The 3D printing technology has demonstrated significant potential in the synthesis of bone substitutes,offering consistent mechanical properties and ease of use.It has found extensive applications in personalized implant customization,prosthetic limb manufacturing,surgical tool production,tissue engineering,biological modeling,and cell diagnostics.Simultaneously,3D bioprinting provides an effective solution to address the issue of organ donor shortage.However,challenges still exist in material selection,management of structural complexity,integration of different cell types,and construction of functionally mature tissues.With advancements in multi-material printing techniques as well as bioprinting and 4D printing technologies emerging on the horizon;3D printing holds immense prospects for revolutionizing the means by which infectious bone defects are repaired.
文摘Bone defects represent a significant clinical challenge with diverse etiologies,including but not limited to tumors,trauma,necrosis,and congenital deformities,imposing substantial patient suffering and socioeconomic burdens.In recent years,novel approaches for bone defect repair have been continuously explored.Biodegradable synthetic materials,particularly those capable of gradual decomposition during tissue regeneration processes,are recognized as ideal candidates for bone repair implants.Natural or synthetic polymer-based materials have been extensively employed in osteochondral repair due to their favorable biocompatibility.Furthermore,biodegradable magnesium(Mg)-based metals constitute another crucial category of bone substitutes.Mg alloys demonstrate unique advantages,including tunable degradation rates,excellent biocompatibility,appropriate mechanical strength,and remarkable osteogenic potential,positioning Mgcontaining implants as a pivotal direction in bone regenerative medicine.However,clinical applications of Mg alloys still face challenges such as rapid degradation kinetics and insufficient osteogenic performance.Further investigation into advanced application strategies for Mg alloys holds significant clinical implications for bone defect therapeutics.
文摘Management of post-traumatic long-bone defects remains relevant and cha-llenging despite the rapid development of approaches to their treatment.Do-minant positions are occupied by the Ilizarov method,bone autogenous grafting and the Masquelet induced membrane technique(IMT).The IMT is aimed at reducing extensive defect treatment duration and for this reason has gained great popularity.However,the assessment of its effectiveness is difficult due to a limited number of clinical series.The varying clinical manifestations of bone defect severity do not allow a comprehensive evaluation of IMT effectiveness.One of them is infection in the defect area.The purpose of our literature review is an analysis of studies on IMT application in infected vs non-infected long-bone defects of the lower extremities published over the last 10 years.It focuses on the investigation of similarities and fundamental differences in the need for antibiotics,timing of spacer fixation,methods of collecting donor bone and fixators used for consolidation.The studies show that the IMT has been globally used in aseptic and osteomyelitic defects due to its clinical effectiveness.Authors’variations and improvements in its practical implementation indicate the ongoing development and the interest of researchers in this technique.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.NRF-2022R1A4A1028747 and RS-2024-00344151).
文摘Recent advances in bone regeneration have introduced the concept of four-dimensional(4D)scaffolds that can undergo morphological and functional changes in response to external stimuli.While several studies have proposed patient-specific designs for defect sites,they often fail to adequately distinguish the advantages of 4D scaffolds over conventional 3D counterparts.This study aimed to investigate the potential benefits of 4D scaffolds in clinically challenging scenarios involving curved defects,where fixation is difficult.We proposed the use of Shape-Memory Polymers(SMPs)as a solution to address critical issues in personalized scaffold fabrication,including dimensional accuracy,measurement error,and manufacturing imprecision.Experimental results demonstrated that the Curved-Layer Fused Deposition Modeling(CLFDM)scaffold,which offers superior conformability to curved defects,achieved significantly higher interfacial contact with the defect area compared to traditional Fused Deposition Modeling(FDM)scaffolds.Specifically,the CLFDM scaffold facilitated bone regeneration of 25.59±4.72 mm^(3),which is more than twice the 9.37±1.36 mm^(3)observed with the 3D FDM scaffold.Furthermore,the 4D CLFDM scaffold achieved 75.38±11.65 mm^(3)of new bone formation after four weeks,approximately three times greater than that of the 3D CLFDM scaffold,regardless of surface micro-roughness.These results underscore that improved geometrical conformity between the scaffold and the defect site enhances cellular infiltration and contributes to more effective bone regeneration.The findings also highlight the promise of 4D scaffolds as a compelling strategy to overcome geometric and dimensional mismatches in the design of patient-specific scaffolds.
文摘This study aimed to utilize micro-computed tomography （micro-CT） analysis to compare new bone formation in rat calvarial defects using chitosan/fibroin-hydroxyapatite （CFB-HAP） or collagen （Bio-Gide） membranes. Fifty-four （54） rats were studied. A circular bony defect （8 mm diameter） was formed in the centre of the calvaria using a trephine bur. The CFB-HAP membrane was prepared by thermally induced phase separation. In the experimental group （n= 18）, the CFB-HAP membrane was used to cover the bony defect, and in the control group （n= 18）, a resorbable collagen membrane （Bio-Gide） was used. In the negative control group （n= 18）, no membrane was used. In each group, six animals were euthanized at 2, 4 and 8 weeks after surgery. The specimens were then analysed using micro-CT. There were significant differences in bone volume （BV） and bone mineral density （BMD） （P〈O.05） between the negative control group and the membrane groups. However, there were no significant differences between the CFB-HAP group and the collagen group. We concluded that the CFB-HAP membrane has significant potential as a guided bone regeneration （GBR） membrane.
基金supported by the Science and Technology Development Plan Project Fund of Jilin Province in China,No.20110492
文摘We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects.To test this,we established rabbit models of 30 mm sciatic nerve defects,and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells.We compared the tensile properties,electrophysiological function and morphology of the damaged nerve in each group.Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone,and produced similar results to those observed with the autograft.These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects.
文摘BACKGROUND Ilizarov non-free bone plasty is a method of distraction osteogenesis using the Ilizarov apparatus for external fixation which originated in Russia and was disseminated across the world. It has been used in long bone defect and nonunion management along with free vascularized grafting and induced membrane technique. However, the shortcomings and problems of these methods still remain the issues which restrict their overall use.AIM To study the recent available literature on the role of Ilizarov non-free bone plasty in long bone defect and nonunion management, its problems and the solutions to these problems in order to achieve better treatment outcomes.METHODS Three databases(Pub Med, Scopus, and Web of Science) were searched for literature sources on distraction osteogenesis, free vascularized grafting and induced membrane technique used in long bone defect and nonunion treatment within a five-year period(2015-2019). Full-text clinical articles in the English language were selected for analysis only if they contained treatment results,complications and described large patient samples(not less than ten cases for congenital, post-tumor resection cases or rare conditions, and more than 20 cases for the rest). Case reports were excluded.RESULTS Fifty full-text articles and reviews on distraction osteogenesis were chosen.Thirty-five clinical studies containing large series of patients treated with this method and problems with its outcome were analyzed. It was found that distraction osteogenesis techniques provide treatment for segmental bone defects and nonunion of the lower extremity in many clinical situations, especially in complex problems. The Ilizarov techniques treat the triad of problems simultaneously(bone loss, soft-tissue loss and infection). Management of tibial defects mostly utilizes the Ilizarov circular fixator. Monolateral fixators are preferable in the femur. The use of a ring fixator is recommended in patients with an infected tibial bone gap of more than 6 cm. High rates of successful treatment were reported by the authors that ranged from 77% to 100% and depended on the pathology and the type of Ilizarov technique used. Hybrid fixation and autogenous grafting are the most applicable solutions to avoid after-frame regenerate fracture or deformity and docking site nonunion.CONCLUSION The role of Ilizarov non-free bone plasty has not lost its significance in the treatment of segmental bone defects despite the shortcomings and treatment problems encountered.
基金King Saud University,through Vice Deanship of Research Chairs
文摘The aim of the present real time in vivo micro-computed tomography （pCT） and histologic experiment was to assess the efficacy of guided bone regeneration （GBR） around standardized calvarial critical size defects （CSD） using bone marrow-derived mesenchymal stem cells （BMSCs）, and collagen membrane （CM） with and without tricalcium phosphate （TCP） graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD （diameter 4.6 mm） were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone （NFB） and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo pCT. At the lOth week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups I and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical ＂lock＂ between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adiunct BMSC therapy.
基金supported by a grant from the National High Technology Research and Development Program of China(863 Program)(NO.2011AA030101)
文摘Summary： This study evaluated the clinical effect of impaction bone graft and distal press-fit fixation for the reconstruction of severe femoral bone defect in revision total hip arthroplasty. A total of 234 patients （involving 236 hips） with Paprosky III and 1V femoral bone defects were treated with the revision total hip arthroplasty from June 1998 to Aug. 2006. Impaction bone graft technique was used for 112 hips, with allogeneic freeze-dried bone as bone graft and SP II as prosthesis. With 124 hips, modular distal press-fit fixation and tapered femoral stem （MP stem） were employed. After the operation, the subjects were followed up on regular basis and results were assessed by using the Harris Hip Score （HHS） and 12-item Short Form Health Survey （SF-12）. Radiolucence, subsidence and loosening were observed and complications, including infection, fracture, dislocation etc. were recorded. A 6-14-year follow-up showed that prostheses failed, due to infection, in 4 patients of impaction bone graft group and that 6 patients in the press-fit fixation group experienced prosthesis failure, with the survival rates for the two techniques being 96.43% and 95.16%, respectively. One-way ANOVA showed that prosthesis survival was significantly associated with surgery-related complications （P〈0.05） and was not related to the type of the bone defects （P〉0.05）. The rate of complications bore significant association with the type of bone defects in the two groups （P〈0.05）. Our study showed that the two revision methods could achieve satisfactory mid-term and long-term results for the reconstruction of severe bone defects. It is of great significance for attaining high prosthesis survival rate to select suitable operation on the basis of the type of bone defect. Careful operative manipulation and post-operative rehabilitation aimed at reducing complications are also important.
基金supported by Science and Technology Projects Fund of Nanjing Medical University(NY0522)
文摘Objective：To study the possibility of natural hydroxyapatite/chitosan composite on repairing bone defects. Methods：We developed a natural hydroxyapatite/chitosan composite that could be molded into any desired shape. The powder component consists of natural hydroxyapatite, which is epurated from bone of pigs. The liquid component consists of malic acid and chitosan. Operations were performed on the left tibias of 15 white rabbits to create two square bone defects. One of the defects was reconstructed with the composite, while the other was not repaired and used as a blank control. Three of the animals were killed at the end of 2 weeks, 4 weeks, 8 weeks, 12 weeks and 16 weeks respectively and implants were evaluated anatomically and histologically. Results：No apparent rejection reaction was found, except for a mild inflammatory infiltration observed 2 weeks after surgery. Fibrous tissue became thinner 2 -8 weeks after surgery and bony connections were detected 12 weeks after surgery. The new bone was the same as the recipient bone by the 16th postoperative week. Conclusion：The hydroxyapatite/chitosan composite has good biocompatibility and osteoconduction. It is a potential repairing material for clinical application.
文摘BACKGROUND Critically sized bone defects represent a significant challenge to orthopaedic surgeons worldwide.These defects generally result from severe trauma or resection of a whole large tumour.Autologous bone grafts are the current gold standard for the reconstruction of such defects.However,due to increased patient morbidity and the need for a second operative site,other lines of treatment should be introduced.To find alternative unconventional therapies to manage such defects,bone tissue engineering using a combination of suitable bioactive factors,cells,and biocompatible scaffolds offers a promising new approach for bone regeneration.AIM To evaluate the healing capacity of platelet-rich fibrin(PRF)membranes seeded with allogeneic mesenchymal bone marrow-derived stem cells(BMSCs)on critically sized mandibular defects in a rat model.METHODS Sixty-three Sprague Dawley rats were subjected to bilateral bone defects of critical size in the mandibles created by a 5-mm diameter trephine bur.Rats were allocated to three equal groups of 21 rats each.Group I bone defects were irrigated with normal saline and designed as negative controls.Defects of group II were grafted with PRF membranes and served as positive controls,while defects of group III were grafted with PRF membranes seeded with allogeneic BMSCs.Seven rats from each group were killed at 1,2 and 4 wk.The mandibles were dissected and prepared for routine haematoxylin and eosin(HE)staining,Masson's trichrome staining and CD68 immunohistochemical staining.RESULTS Four weeks postoperatively,the percentage area of newly formed bone was significantly higher in group III(0.88±0.02)than in groups I(0.02±0.00)and II(0.60±0.02).The amount of granulation tissue formation was lower in group III(0.12±0.02)than in groups I(0.20±0.02)and II(0.40±0.02).The number of inflammatory cells was lower in group III(0.29±0.03)than in groups I(4.82±0.08)and II(3.09±0.07).CONCLUSION Bone regenerative quality of critically sized mandibular bone defects in rats was better promoted by PRF membranes seeded with BMSCs than with PRF membranes alone.
文摘TGF-β is a multifunctional cytokine that regulates many aspects of cellular function, including periosteal mesenchymal cell proliferation, differentiation. This experiment is to study its effects on bone defect repair. A rabbit radial bone defect model was used to evaluate the effect of TGF-β, which was extracted and purified from bovine blood platelets, on the healing of a large segmental osteoperiosteal defect. A 1. 5-centimeter segmental defect was created in the mid-upper part of the radial shaft of adult rabbits. The defect was filled with implant containing TGF-β that consisted of carrier and bovine TGF-β. Limbs served as controls received carrier alone. The defectswere examined radiographically and histologically at 4, 8,12 , 16 and 20 weeks after implantation. The results showed that in TGF-β implant group . the defect areas at 12 weeks post operation were bridged by uniform new bone and the cut ends of cortex could not be seen;while in control group, the defects remained clear. Only a small amount of new bone formed as a cap on the cut bone ends. In the experimental group, new lamellar and woven bone formed in continuity with the cut ends of the cortex. An early medullar canal appears to be forming and contained normal-appearancing marrow elements; while the control group displayed entirely fibrous tissue within the defect site. Remnants of the cancellous bone carrier were observed in the control specimen. These data demonstrate that exogenous TGF-β initiate osteogenesis and stimulate the bone defects repair in animal model.
基金financially supported by National Natural Science Foundation of China(Nos.31525009 and 31271021)National 863 Project(No.2015AA020316)+2 种基金Sichuan Innovative Research Team Program for Young Scientists(No.2016TD0004)Zhejiang Provincial Science and Technology Grant(No.2017C33100)Zhejiang Provincial Natural Science Foundation of China(No.LY17H060010)
文摘Periosteum is a thin membrane that encases the surfaces of most bones.It is composed of an outer fibrous layer contains longitudinally oriented cells and collagen fibers and an inner cambial layer that consists of multipotent mesenchymal stem cells（MSCs）and osteogenic progenitor cells.Periosteum has a function of regulating cell and collagen arrangement,which is important to the integrity,modelling and remodelling of bone,particularly during bone defect repair.Apart from autograft and allograft,artificial periosteum,or tissue-engineered periosteum mimicking native periosteum in structure or function,made up of small intestinal submucosa,acellular dermis,induced membrane,cell sheets,and polymeric scaffolds,and so on,has been developed to be used in bone defect repair.In this review,we classify the artificial periosteum into three approaches based on the material source,that is,native tissues,scaffoldfree cell sheets and scaffold-cell composites.Mechanisms,methods and efficacy of each approach are provided.Existing obstacles and enabling technologies for future directions are also discussed.
