The healing of critical-sized bone defects(CSD)remains a challenge in orthopedic medicine.In recent years,scaffolds with sophisticated microstructures fabricated by the emerging three-dimensional(3D)printing technolog...The healing of critical-sized bone defects(CSD)remains a challenge in orthopedic medicine.In recent years,scaffolds with sophisticated microstructures fabricated by the emerging three-dimensional(3D)printing technology have lighted up the treatment of the CSD due to the elaborate microenvironments and support they may build.Here,we established a magnesium oxide-reinforced 3D-printed biocompos-ite scaffold to investigate the effect of magnesium-enriched 3D microenvironment on CSD repairing.The composite was prepared using a biodegradable polymer matrix,polycaprolactone(PCL),and the disper-sion phase,magnesium oxide(MgO).With the appropriate surface treatment by saline coupling agent,the MgO dispersed homogeneously in the polymer matrix,leading to enhanced mechanical performance and steady release of magnesium ion(Mg^(2+))for superior cytocompatibility,higher cell viability,advanced osteogenic differentiation,and cell mineralization capabilities in comparison with the pure PCL.The in-vivo femoral implantation and critical-sized cranial bone defect studies demonstrated the importance of the 3D magnesium microenvironment,as a scaffold that released appropriate Mg^(2+) exhibited remarkably increased bone volume,enhanced angiogenesis,and almost recovered CSD after 8-week implantation.Overall,this study suggests that the magnesium-enriched 3D scaffold is a potential candidate for the treatment of CSD in a cell-free therapeutic approach.展开更多
The impact of orthopedic scaffolds on bone defect healing,particularly the late-stage bone remodeling process,is pivotal for the therapeutic outcome.This study applies fadditively manufactured scaffolds composed of hy...The impact of orthopedic scaffolds on bone defect healing,particularly the late-stage bone remodeling process,is pivotal for the therapeutic outcome.This study applies fadditively manufactured scaffolds composed of hydroxyapatite-doped poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide)(HAPELGA)with varying properties to treat rat calvarial defects,elucidating their significant role in bone remodeling by modulating physiological responses.We engineered two scaffolds with different polylactic acid(PLA)to polyglycolic acid(PGA)ratio(9/1 and 18/1)to vary in hydrophobicity,degradation rate,mechanical properties,and structural stability.These variations influenced physiological responses,including osteogenesis,angiogen-esis,and immune reactions,thereby guiding bone remodeling.Our findings show that the HA-PELGA(18/1)scaffold,with a slower degradation rate,supported bulk bone formation due to a stable microenvironment.Conversely,the HA-PELGA(9/1)scaffold,with a faster degradation rate and more active interfaces,facilitated the formation of a thin bone layer and higher bone infiltration.This study demonstrates these degradable scaffolds help to promote bone healing and reveals how scaffold properties influence the bone remodeling process,offering a potential strategy to optimize scaffold design aiming at late-stage bone defect healing.展开更多
Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures.Biodegradable Zn metals are revolutionary materials for orthopedic implants.In this...Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures.Biodegradable Zn metals are revolutionary materials for orthopedic implants.In this study,pure Zn porous scaffolds with diamond structures were fabricated using customized laser powder bed fusion(L-PBF)technology.First,the mechanical properties,corrosion behavior,and biocompatibility of the pure Zn porous scaffolds were characterized in vitro.The scaffolds were then implanted into the rabbit femur critical-size bone defect model for 24 weeks.The results showed that the pure Zn porous scaffolds had compressive strength and rigidity comparable to those of cancellous bone,as well as relatively suitable degradation rates for bone regeneration.A benign host response was observed using hematoxylin and eosin(HE)staining of the heart,liver,spleen,lungs,and kidneys.Moreover,the pure Zn porous scaffold showed good biocompatibility and osteogenic promotion ability in vivo.This study showed that pure Zn porous scaffolds with customized structures fabricated using L-PBF represent a promising biodegradable solution for treating large bone defects.展开更多
A novel biodegradable metal system,ZnLiCa ternary alloys,were systematically investigated both in vitro and in vivo.The ultimate tensile strength(UTS)of Zn0.8Li0.1Ca alloy reached 567.60±9.56 MPa,which is compara...A novel biodegradable metal system,ZnLiCa ternary alloys,were systematically investigated both in vitro and in vivo.The ultimate tensile strength(UTS)of Zn0.8Li0.1Ca alloy reached 567.60±9.56 MPa,which is comparable to pure Ti,one of the most common material used in orthopedics.The elongation of Zn0.8Li0.1Ca is 27.82±18.35%,which is the highest among the ZnLiCa alloys.The in vitro degradation rate of Zn0.8Li0.1Ca alloy in simulated body fluid(SBF)showed significant acceleration than that of pure Zn.CCK-8 tests and hemocompatibility tests manifested that ZnLiCa alloys exhibit good biocompatibility.Real-time PCR showed that Zn0.8Li0.1Ca alloy successfully stimulated the expressions of osteogenesis-related genes(ALP,COL-1,OCN and Runx-2),especially the OCN.An in vivo implantation was conducted in the radius of New Zealand rabbits for 24 weeks,aiming to treat the bone defects.The Micro-CT and histological evaluations proved that the regeneration of bone defect was faster within the Zn0.8Li0.1Ca alloy scaffold than the pure Ti scaffold.Zn0.8Li0.1Ca alloy showed great potential to be applied in orthopedics,especially in the load-bearing sites.展开更多
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
In clinical settings,regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods,restricted bone growth medications,and a scarcity of commercial bone gra...In clinical settings,regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods,restricted bone growth medications,and a scarcity of commercial bone grafts.To treat this life-threatening issue,improved biofunctional grafts capable of properly healing critical-sized bone defects are required.In this study,we effectively created anti-fracture hydrogel systems using spongy-like metal-organic(magnesium-phosphate)coordinated chitosan-modified injectable hydrogels(CPMg)loaded with a bioinspired neobavaisoflavone(NBF)component.The CPMg-NBF hydrogels showed outstanding anti-fracture capabilities during compression testing and retained exceptional mechanical stability even after 28 d of immersion in phosphatebuffered saline.They also demonstrated prolonged and stable release profiles of Mg^(2+)and NBF.Importantly,CPMg-NBF hydrogels revealed robust biphasic mineralization and were non-toxic to MC3T3-E1 cells.To better understand the underlying mechanism of Mg^(2+)and NBF component,as well as their synergistic effect on osteogenesis,we investigated the expression of key osteogenic proteins in the p38 MAPK and NOTCH pathways.Our results showed that CPMg-NBF hydrogels greatly increased the expression of osteogenic proteins(Runx2,OCN,OPN,BMPS and ALP).In vivo experiments showed that the implantation of CPMg-NBF hydrogels resulted in a significant increase in new bone growth within critical-sized calvarial defects.Based on these findings,we expect that the CPMg-NBF supramolecular hydrogel has tremendous promise for use as a therapeutic biomaterial for treating critical-sized calvarial defects.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
Physiological repair of large-sized bone defects requires instructive scaffolds with appropriate mechanical properties,biocompatibility,biodegradability,vasculogenic ability and osteo-inductivity.The objective of this...Physiological repair of large-sized bone defects requires instructive scaffolds with appropriate mechanical properties,biocompatibility,biodegradability,vasculogenic ability and osteo-inductivity.The objective of this study was to fabricate in situ injectable hydrogels using platelet-rich plasma(PRP)-loaded gelatin methacrylate(GM)and employ them for the regeneration of large-sized bone defects.We performed various biological assays as well as assessed the mechanical properties of GM@PRP hydrogels alongside evaluating the release kinetics of growth factors(GFs)from hydrogels.The GM@PRP hydrogels manifested sufficient mechanical properties to support the filling of the tissue defects.For biofunction assay,the GM@PRP hydrogels significantly improved cell migration and angiogenesis.Especially,transcriptome RNA sequencing of human umbilical vein endothelial cells and bone marrow-derived stem cells were performed to delineate vascularization and biomineralization abilities of GM@PRP hydrogels.The GM@PRP hydrogels were subcutaneously implanted in rats for up to 4 weeks for preliminary biocompatibility followed by their transplantation into a tibial defect model for up to 8 weeks in rats.Tibial defects treated with GM@PRP hydrogels manifested significant bone regeneration as well as angiogenesis,biomineralization,and collagen deposition.Based on the biocompatibility and biological function of GM@PRP hydrogels,a new strategy is provided for the regenerative repair of large-size bone defects.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
The custom-tailored medicine requires a developmental strategy that integrates excellent osteogene-sis with mechanical stability to enhance the reconstruction of the critical-size bone defect(CSBD)and the healing proc...The custom-tailored medicine requires a developmental strategy that integrates excellent osteogene-sis with mechanical stability to enhance the reconstruction of the critical-size bone defect(CSBD)and the healing process in weight-bearing bone.We prepared three-dimensional(3D)printed biphasic cal-cium phosphate(BCP)scaffolds composited with nano-graphene oxide(GO).The biological effects of the GO/BCP composite scaffolds could induce the differentiation of rat bone marrow stem cells(BM-SCs)and the migration of human umbilical vein endothelial cells(HUVECs)for bone repair.The proper ratio of GO in the composite scaffold regulated the composites’surface roughness and hydrophilicity to a suitable range for the adhesion and proliferation of BMSCs and HUVECs.Besides,the GO/BCP composite scaffold increased osteogenesis and angiogenesis by activating BMP-2,RUNX-2,Smad1/4,and VEGF.The customized intramedullary nail combined with GO/BCP scaffold was applied to repair CSBD(2.0 cm in length)in a beagle femur model.This fixation strategy was confirmed by finite element analysis.In vivo,the results indicated that the custom-made internal fixation provided sufficient stability in the early stage,ensuring bone healing in a considerable mechanical environment.At 9 months postoperatively,longitudi-nal bony union and blood vessels in osteon were observed in the CSBD area with partial degradation in the 0.3%GO/BCP group.In the three-point bending test,the ultimate load of 0.3%GO/BCP group reached over 50%of the normal femur at 9 months after repair.These results showed a promising application of osteogenic GO/BCP scaffold and custom-made intramedullary nails in repairing CSBD of the beagle femur.This effective strategy could provide an option to treat the clinical CSBD in weight-bearing bones.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
基金The authors would like to thank Li LI and H.Z.Xie for the technical support.This work was financially supported by the National Natural Science Foundation of China(Nos.82002303 and 81702171)the Guangdong Basic and Applied Basic Research Foundation(Nos.2022A1515011536,2021A1515220093,2021A1515220086,2019A1515111156,and 2022A1515011815)+7 种基金the Scientific Research Foundation of Peking University Shenzhen hospital(No.KYQD2021064)the Health and Medical Research Fund(No.19180712)the Shenzhen Double Chain Project for Innovation and Development Industry supported by the Bureau of Industry and Information Technology of Shenzhen(No.201806081018272960)the Shenzhen Science and Technology Innovation Committee Projects(Nos.JCYJ20190809182213535 and JSGG20180507183242702)the program from Shanghai Municipal Health Commission(No.201740165)the National Key R&D Program of China(No.2018YFC1105100)the Hong Kong Innovation Technology Fund(Nos.ITS/287/17 and ITS/405/18)the Hong Kong Research Grant Council General Research Fund(No.17214516).
文摘The healing of critical-sized bone defects(CSD)remains a challenge in orthopedic medicine.In recent years,scaffolds with sophisticated microstructures fabricated by the emerging three-dimensional(3D)printing technology have lighted up the treatment of the CSD due to the elaborate microenvironments and support they may build.Here,we established a magnesium oxide-reinforced 3D-printed biocompos-ite scaffold to investigate the effect of magnesium-enriched 3D microenvironment on CSD repairing.The composite was prepared using a biodegradable polymer matrix,polycaprolactone(PCL),and the disper-sion phase,magnesium oxide(MgO).With the appropriate surface treatment by saline coupling agent,the MgO dispersed homogeneously in the polymer matrix,leading to enhanced mechanical performance and steady release of magnesium ion(Mg^(2+))for superior cytocompatibility,higher cell viability,advanced osteogenic differentiation,and cell mineralization capabilities in comparison with the pure PCL.The in-vivo femoral implantation and critical-sized cranial bone defect studies demonstrated the importance of the 3D magnesium microenvironment,as a scaffold that released appropriate Mg^(2+) exhibited remarkably increased bone volume,enhanced angiogenesis,and almost recovered CSD after 8-week implantation.Overall,this study suggests that the magnesium-enriched 3D scaffold is a potential candidate for the treatment of CSD in a cell-free therapeutic approach.
文摘The impact of orthopedic scaffolds on bone defect healing,particularly the late-stage bone remodeling process,is pivotal for the therapeutic outcome.This study applies fadditively manufactured scaffolds composed of hydroxyapatite-doped poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide)(HAPELGA)with varying properties to treat rat calvarial defects,elucidating their significant role in bone remodeling by modulating physiological responses.We engineered two scaffolds with different polylactic acid(PLA)to polyglycolic acid(PGA)ratio(9/1 and 18/1)to vary in hydrophobicity,degradation rate,mechanical properties,and structural stability.These variations influenced physiological responses,including osteogenesis,angiogen-esis,and immune reactions,thereby guiding bone remodeling.Our findings show that the HA-PELGA(18/1)scaffold,with a slower degradation rate,supported bulk bone formation due to a stable microenvironment.Conversely,the HA-PELGA(9/1)scaffold,with a faster degradation rate and more active interfaces,facilitated the formation of a thin bone layer and higher bone infiltration.This study demonstrates these degradable scaffolds help to promote bone healing and reveals how scaffold properties influence the bone remodeling process,offering a potential strategy to optimize scaffold design aiming at late-stage bone defect healing.
基金supported by the National Key R&D Program of China[grant number 2018YFE0104200]the National Natural Science Foundation of China[grant numbers 51901003,51931001,52171233,51875310]+1 种基金the Beijing Natural Science Foundation[grant number L212014]the Open Project of NMPA Key Laboratory for Dental Materials[grant number PKUSS20200401].
文摘Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures.Biodegradable Zn metals are revolutionary materials for orthopedic implants.In this study,pure Zn porous scaffolds with diamond structures were fabricated using customized laser powder bed fusion(L-PBF)technology.First,the mechanical properties,corrosion behavior,and biocompatibility of the pure Zn porous scaffolds were characterized in vitro.The scaffolds were then implanted into the rabbit femur critical-size bone defect model for 24 weeks.The results showed that the pure Zn porous scaffolds had compressive strength and rigidity comparable to those of cancellous bone,as well as relatively suitable degradation rates for bone regeneration.A benign host response was observed using hematoxylin and eosin(HE)staining of the heart,liver,spleen,lungs,and kidneys.Moreover,the pure Zn porous scaffold showed good biocompatibility and osteogenic promotion ability in vivo.This study showed that pure Zn porous scaffolds with customized structures fabricated using L-PBF represent a promising biodegradable solution for treating large bone defects.
基金National Natural Science Foundation of China(Grant No.51931001)International Cooperation and Exchange project between NSFC(China)and CNR(Italy)(NSFC-CNR Grant No.52011530392).
文摘A novel biodegradable metal system,ZnLiCa ternary alloys,were systematically investigated both in vitro and in vivo.The ultimate tensile strength(UTS)of Zn0.8Li0.1Ca alloy reached 567.60±9.56 MPa,which is comparable to pure Ti,one of the most common material used in orthopedics.The elongation of Zn0.8Li0.1Ca is 27.82±18.35%,which is the highest among the ZnLiCa alloys.The in vitro degradation rate of Zn0.8Li0.1Ca alloy in simulated body fluid(SBF)showed significant acceleration than that of pure Zn.CCK-8 tests and hemocompatibility tests manifested that ZnLiCa alloys exhibit good biocompatibility.Real-time PCR showed that Zn0.8Li0.1Ca alloy successfully stimulated the expressions of osteogenesis-related genes(ALP,COL-1,OCN and Runx-2),especially the OCN.An in vivo implantation was conducted in the radius of New Zealand rabbits for 24 weeks,aiming to treat the bone defects.The Micro-CT and histological evaluations proved that the regeneration of bone defect was faster within the Zn0.8Li0.1Ca alloy scaffold than the pure Ti scaffold.Zn0.8Li0.1Ca alloy showed great potential to be applied in orthopedics,especially in the load-bearing sites.
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 Natural Science Foundation of China(No.82202664,82172432,U22A20371)Shenzhen Sustainable Development Project(No.KCXFZ20201221173411031)+4 种基金Shenzhen Science and Technology Program(JCYJ20220818102815033,National Science Foundation of Guangdong Province(No.2021A1515220053,2022A1515010034,2021B1515120061)Guangdong Basic and Applied Basic Research Foundation(No.2019A1515110983,2022A1515012663)Guangzhou Basic and Applied Basic Research Foundation(202102021160)the Fundamental Research Funds for the Central Universities(21624221)the Research Fund Program of Guangdong Provincial Key Laboratory of Speed Capability Research(2023B1212010009).
文摘In clinical settings,regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods,restricted bone growth medications,and a scarcity of commercial bone grafts.To treat this life-threatening issue,improved biofunctional grafts capable of properly healing critical-sized bone defects are required.In this study,we effectively created anti-fracture hydrogel systems using spongy-like metal-organic(magnesium-phosphate)coordinated chitosan-modified injectable hydrogels(CPMg)loaded with a bioinspired neobavaisoflavone(NBF)component.The CPMg-NBF hydrogels showed outstanding anti-fracture capabilities during compression testing and retained exceptional mechanical stability even after 28 d of immersion in phosphatebuffered saline.They also demonstrated prolonged and stable release profiles of Mg^(2+)and NBF.Importantly,CPMg-NBF hydrogels revealed robust biphasic mineralization and were non-toxic to MC3T3-E1 cells.To better understand the underlying mechanism of Mg^(2+)and NBF component,as well as their synergistic effect on osteogenesis,we investigated the expression of key osteogenic proteins in the p38 MAPK and NOTCH pathways.Our results showed that CPMg-NBF hydrogels greatly increased the expression of osteogenic proteins(Runx2,OCN,OPN,BMPS and ALP).In vivo experiments showed that the implantation of CPMg-NBF hydrogels resulted in a significant increase in new bone growth within critical-sized calvarial defects.Based on these findings,we expect that the CPMg-NBF supramolecular hydrogel has tremendous promise for use as a therapeutic biomaterial for treating critical-sized calvarial defects.
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.
基金funded by Donghua University Postgraduate Innovation and Entrepreneurship Ability Training Program(yjssc2023002)supported by Science and Technology Commission of Shanghai Municipality,China(grant numbers 20S31900900 and 20DZ2254900)+1 种基金Sino German Science Foundation Research Exchange Center,China(M-0263)China Education Association for International Exchange(2022181).
文摘Physiological repair of large-sized bone defects requires instructive scaffolds with appropriate mechanical properties,biocompatibility,biodegradability,vasculogenic ability and osteo-inductivity.The objective of this study was to fabricate in situ injectable hydrogels using platelet-rich plasma(PRP)-loaded gelatin methacrylate(GM)and employ them for the regeneration of large-sized bone defects.We performed various biological assays as well as assessed the mechanical properties of GM@PRP hydrogels alongside evaluating the release kinetics of growth factors(GFs)from hydrogels.The GM@PRP hydrogels manifested sufficient mechanical properties to support the filling of the tissue defects.For biofunction assay,the GM@PRP hydrogels significantly improved cell migration and angiogenesis.Especially,transcriptome RNA sequencing of human umbilical vein endothelial cells and bone marrow-derived stem cells were performed to delineate vascularization and biomineralization abilities of GM@PRP hydrogels.The GM@PRP hydrogels were subcutaneously implanted in rats for up to 4 weeks for preliminary biocompatibility followed by their transplantation into a tibial defect model for up to 8 weeks in rats.Tibial defects treated with GM@PRP hydrogels manifested significant bone regeneration as well as angiogenesis,biomineralization,and collagen deposition.Based on the biocompatibility and biological function of GM@PRP hydrogels,a new strategy is provided for the regenerative repair of large-size bone defects.
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This work was financially supported,in part,by the Sci-ence and Technology Research Program of Sichuan Province(No.2020YFS0036,Dr.Tu)the 1·3·5 project for disciplines of excel-lence,West China Hospital,Sichuan University(No.ZYJC18036,Dr.Tu).
文摘The custom-tailored medicine requires a developmental strategy that integrates excellent osteogene-sis with mechanical stability to enhance the reconstruction of the critical-size bone defect(CSBD)and the healing process in weight-bearing bone.We prepared three-dimensional(3D)printed biphasic cal-cium phosphate(BCP)scaffolds composited with nano-graphene oxide(GO).The biological effects of the GO/BCP composite scaffolds could induce the differentiation of rat bone marrow stem cells(BM-SCs)and the migration of human umbilical vein endothelial cells(HUVECs)for bone repair.The proper ratio of GO in the composite scaffold regulated the composites’surface roughness and hydrophilicity to a suitable range for the adhesion and proliferation of BMSCs and HUVECs.Besides,the GO/BCP composite scaffold increased osteogenesis and angiogenesis by activating BMP-2,RUNX-2,Smad1/4,and VEGF.The customized intramedullary nail combined with GO/BCP scaffold was applied to repair CSBD(2.0 cm in length)in a beagle femur model.This fixation strategy was confirmed by finite element analysis.In vivo,the results indicated that the custom-made internal fixation provided sufficient stability in the early stage,ensuring bone healing in a considerable mechanical environment.At 9 months postoperatively,longitudi-nal bony union and blood vessels in osteon were observed in the CSBD area with partial degradation in the 0.3%GO/BCP group.In the three-point bending test,the ultimate load of 0.3%GO/BCP group reached over 50%of the normal femur at 9 months after repair.These results showed a promising application of osteogenic GO/BCP scaffold and custom-made intramedullary nails in repairing CSBD of the beagle femur.This effective strategy could provide an option to treat the clinical CSBD in weight-bearing bones.
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.
