Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering applications.The use of advanced ...Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering applications.The use of advanced image acquisition techniques,image processing,and computer-aided design methods has enabled the precise design and additive manufacturing of anatomically correct and patient-specific implants and scaffolds.However,these sophisticated techniques can be timeconsuming,labor-intensive,and expensive.Moreover,the necessary imaging and manufacturing equipment may not be readily available when urgent treatment is needed for trauma patients.In this study,a novel design and AM methods are proposed for the development of modular and customizable scaffold blocks that can be adapted to fit the bone defect area of a patient.These modular scaffold blocks can be combined to quickly form any patient-specific scaffold directly from two-dimensional(2D)medical images when the surgeon lacks access to a 3D printer or cannot wait for lengthy 3D imaging,modeling,and 3D printing during surgery.The proposed method begins with developing a bone surface-modeling algorithm that reconstructs a model of the patient’s bone from 2D medical image measurements without the need for expensive 3D medical imaging or segmentation.This algorithm can generate both patient-specific and average bone models.Additionally,a biomimetic continuous path planning method is developed for the additive manufacturing of scaffolds,allowing porous scaffold blocks with the desired biomechanical properties to be manufactured directly from 2D data or images.The algorithms are implemented,and the designed scaffold blocks are 3D printed using an extrusion-based AM process.Guidelines and instructions are also provided to assist surgeons in assembling scaffold blocks for the self-repair of patient-specific large bone 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
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
The stability parameters of implants (ITV, ISQ & PTV) according to different sizes of controlled bone defects made in implant osteotomies were analyzed and the correlation among the three kinds of implant stability...The stability parameters of implants (ITV, ISQ & PTV) according to different sizes of controlled bone defects made in implant osteotomies were analyzed and the correlation among the three kinds of implant stability parameters was tested in this study. 45 tapped screw-type dental implants were inserted in three types of implant osteotomies made in 8 fresh-frozen pig femoral bones: Typel - without coronal bone defect, Type2 - with 3 mm coronal bone defects, and Type3 - with 6 mm coronal bone defects. The insertion torque values, ISQ & PTV of implants were measured and analyzed statistically. It is concluded that the circumferential coronal bone defects statistically influence the primary stability of implants; ITV, ISQ and PTV are suitable and available to detect the peri-implant coronal bone defects in 3 mm increments, and ITV and PTV are more sensitive to coronal cortical bone loss. There was a strong correlation between ITV and ISQ.展开更多
In order to evaluate the efficacy of low intensity ultrasound and tissue engineering technique to repair segmental bone defects, the rabbit models of 1.5-cm long rabbit radial segmental osteoperiosteum defects were es...In order to evaluate the efficacy of low intensity ultrasound and tissue engineering technique to repair segmental bone defects, the rabbit models of 1.5-cm long rabbit radial segmental osteoperiosteum defects were established and randomly divided into 2 groups. All defects were implanted with the composite of calcium phosphate cement and bone mesenchymal stem cells, and ad- ditionally those in experimental group were subjected to low intensity ultrasound exposure, while those in control group to sham exposure. The animals were killed on the postoperative week 4, 8 and 12 respectively, and specimens were harvested. By using radiography and the methods of biomechanics, histomorphology and bone density detection, new bone formation and material degradation were observed. The results showed that with the prolongation of time after operation, serum alkaline phosphatase (AKP) levels in both groups were gradually increased, especially in experimental group, reached the peak at 6th week (experimental group: 1,26 mmol/L; control group: 0.58 mmol/L), suggesting the new bone formation in both two group, but the amount of new bone formation was greater and bone repairing capacity stronger in experimental group than in control group. On the 4th week in experimental group, chondrocytes differentiated into woven bone, and on the 12th week, remodeling of new lamellar bone and absorption of the composite material were observed. The mechanical strength of composite material and new born density in experimental group were significantly higher than in control group, indicating that low intensity ultrasound could not only effectively increase the formation of new bone, but also accelerate the calcification of new bone. It was concluded that low intensity ultrasound could evidently accelerate the healing of bone defects repaired by bone tissue engineering.展开更多
Objective: To systematically evaluate the clinical efficacy and safety of Masquelet technology and Llizarov group technology in the treatment of infectious bone defects by meta-analysis. Methods: The computer searched...Objective: To systematically evaluate the clinical efficacy and safety of Masquelet technology and Llizarov group technology in the treatment of infectious bone defects by meta-analysis. Methods: The computer searched China Knowledge Network (CNKI), Wanfang, VIP, Chinese Biomedical Literature Database (CBM), Pubmed, Medline, Cochrane Llibrary databases. The retrieval time was from the time of the establishment of the database to January 2020. According to the inclusion and exclusion criteria, randomized controlled trials on the treatment of infectious bone defects using Masquelet technology and Llizarov technology were collected, and the retrieved literature was independently screened, evaluated, and data extracted by two researchers, and then RevMan5.3 software was used so for meta-analysis. Results: A total of 10 RCT documents were included, with a total of 496 patients, including 242 in the Masquelet group and 254 in the Llizarov group. The results of the meta-analysis showed that: in terms of bone defect healing time, total weight bearing time, treatment cost, and complication rate, the Masquelet group was significantly different from the Llizarov group, and the Masquelet group was better than the Llizarov group (P <0.05);In terms of knee joint Lowa score and SF-36 score, Masquelet group has significant differences compared with Llizarov group, Llizarov group is better than Masquelet group (P <0.05);in excellent rate, number of operations, ankle Lowa score, infection control rate In terms of excellent rate of affected limb function, there was no significant difference between Masquelet group and Llizarov group (P> 0.05). Conclusion:Compared with Llizarov technology, Masquelet technology has obvious advantages in the treatment of infectious bone defects in terms of bone defect healing time, total weight-bearing time, treatment cost, and complication rate. In terms of scoring, it has advantages over Masquelet technology, but in terms of excellent treatment rate, number of operations, and ankle lowa score. In terms of infection control rate and excellent function of affected limbs, there was no significant difference between Masquelet technology and Llizarov technology,However, due to the low quality of the included studies and the small sample size, the exact efficacy still needs to be confirmed by higher quality RCT studies.展开更多
Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone regeneration.However,current strategies lack regulation of the specific endogenous cell...Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone regeneration.However,current strategies lack regulation of the specific endogenous cell populations for vascularized bone regeneration,thus leading to adverse tissue formation and decreased regenerative efficiency.Here,we engineered a biomaterial to regulate endogenous cell adhesion and promote vascularized bone regeneration.The biomaterial works by presenting two synthetic ligands,LLP2A and LXW7,explicitly targeting integrinsα4β1 andαvβ3,respectively,expressed on the surfaces of the cells related to bone formation and vascularization,such as mesenchymal stem cells(MSCs),osteoblasts,endothelial progenitor cells(EPCs),and endothelial cells(ECs).In vitro,the LLP2A/LXW7 modified biomaterial improved the adhesion of MSCs,osteoblasts,EPCs,and ECs via integrinα4β1 andαvβ3,respectively.In an adult rat calvarial bone defect model,the LLP2A/LXW7 modified biomaterial enhanced bone formation and vascularization by synergistically regulating endogenous cells with osteogenic and angiogenic potentials,such as DLX5^(+)cells,osteocalcin^(+)cells,CD34^(+)/CD45-cells and CD31^(+)cells.In a fetal sheep spinal bone defect model,the LLP2A/LXW7 modified biomaterial augmented bone formation and vascularization without any adverse effects.This innovative biomaterial offers an off-the-shelf,easy-to-use,and biologically safe product suitable for vascularized bone regeneration in both fetal and adult disease environments.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
Stem cell-based tissue engineering has provided a promising platform for repairing of bone defects.However,the use of exogenous bone marrow mesenchymal stem cells(BMSCs)still faces many challenges such as limited sour...Stem cell-based tissue engineering has provided a promising platform for repairing of bone defects.However,the use of exogenous bone marrow mesenchymal stem cells(BMSCs)still faces many challenges such as limited sources and potential risks.It is important to develop new approach to effectively recruit endogenous BMSCs and capture them for in situ bone regeneration.Here,we designed an acoustically responsive scaffold(ARS)and embedded it into SDF-1/BMP-2 loaded hydrogel to obtain biomimetic hydrogel scaffold complexes(BSC).The SDF-1/BMP-2 cytokines can be released on demand from the BSC implanted into the defected bone via pulsed ultrasound(p-US)irradiation at optimized acoustic parameters,recruiting the endogenous BMSCs to the bone defected or BSC site.Accompanied by the daily p-US irradiation for 14 days,the alginate hydrogel was degraded,resulting in the exposure of ARS to these recruited host stem cells.Then another set of sinusoidal continuous wave ultrasound(s-US)irradiation was applied to excite the ARS intrinsic resonance,forming highly localized acoustic field around its surface and generating enhanced acoustic trapping force,by which these recruited endogenous stem cells would be captured on the scaffold,greatly promoting them to adhesively grow for in situ bone tissue regeneration.Our study provides a novel and effective strategy for in situ bone defect repairing through acoustically manipulating endogenous BMSCs.展开更多
BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To e...BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.展开更多
Bone is a complex biological tissue with a complicated hierarchical nanocomposite structure.The native microen-vironment of the bone tissue may be significantly disrupted by large physiological and pathological bone d...Bone is a complex biological tissue with a complicated hierarchical nanocomposite structure.The native microen-vironment of the bone tissue may be significantly disrupted by large physiological and pathological bone defects.Bone defects are often treated via complex surgical procedures that involve the application of autografts or al-lografts.While these grafting procedures often suffer from insufficient natural bone stock and immunorejection.Moreover,these traditional treatment methods fail to simulate a regenerative microenvironment,which plays a significant role in regeneration of bone tissue and repair of large bone defects.To this end,various biomimetic scaffolds have been devised to mimic the native microenvironment of bone and thereby to simultaneously re-pair bone defects and promote bone regeneration.We propose here a novel concept,in vivo bone regenerative microenvironment(BRM),which enables repair of large bone defects and enhances new bone tissue formation with external regulation.In this review,we mainly focus on materials and methods for fabrication of biomimetic scaffolds,as well as their therapeutic efficacy in modulating the BRM of large physiological and pathological bone defects.展开更多
Background Gene therapy has been a hot spot in repair of bone defects in recent years. This study aimed to construct a recombinant plasmid pcDNA3.1-VEGF165, and to observe the effect of vascular endothelial growth fac...Background Gene therapy has been a hot spot in repair of bone defects in recent years. This study aimed to construct a recombinant plasmid pcDNA3.1-VEGF165, and to observe the effect of vascular endothelial growth factor 165 (VEGF165) gene therapy on bone defects in rabbits. Methods Total RNA was extracted from rabbit bone tissues. VEGF165 cDNA fragment was prepared by reverse transcription and the gene was cloned by polymerase chain reaction (PCR). Plasmid pMD18-T/VEGF165 combined with pcDNA3.1 was cloned to reconstruct pcDNA3.1-VEGF165 plasmid. Thirty New Zealand white rabbits weighing (2.50±0.13)kg were used to establish models of bone defects (1 cm in length) of the bilateral radii. The bone defects were repaired with absorbable gelatin sponge. After the operation, physiological sodium chloride solution was injected into the injured site in one of the forelegs of the rabbits as the control group, and pcDNA3.1-VEGF165 plasmid (0.2 ml, 200 ng) was injected into the opposite foreleg as the experiment groups. At weeks 1, 2, 4, 6, 8, and 12 after the treatments, the bones were examined by X-ray, and the specimens of the bone defects were collected, stained with HE, and observed under a light microscope. The expression of VEGF165 mRNA was examined by real-time quantitative polymerase chain reaction (RQ-PCR). Results The pcDNA3.1-VEGF165 plasmid with a correct sequence was constructed successfully. Postoperative X-ray found no difference between the two groups at week 1. In the experiment group, callus and synostosis were observed after 2 weeks, and osteosis structure was normal at week 12; these phenomena occurred much later in the control group. In the experiment group, HE staining showed a large amount of newly formed blood vessels after 2 weeks, a number of bone trabeculae with osteoblasts proliferation at 4 weeks, and fresh bone cortex and reformed medullary cavity at 12 weeks; whereas in the control group these structures formed in later phases. The VEGF165 mRNA in the experiment group was expressed at a low level at week 1, reached the peak at weeks 3, and then decreased to a normal level after 6 weeks. Conclusions Local use of pcDNA3.1-VEGF165 plasmid at bone defects can upregulate the expression of VEGF165 and accelerate the formation of capillaries and the repair of bone defects. Angiogenesis and osteogenesis can be promoted by a combination of pcDNA3.1-VEGF165 and gelatin sponge.展开更多
With the population aging and an increasing desire for a high quality of life,millions of patients who suffered knee arthropathy have undergone total knee arthroplasty (TKA).Although the success rate for primary TKA...With the population aging and an increasing desire for a high quality of life,millions of patients who suffered knee arthropathy have undergone total knee arthroplasty (TKA).Although the success rate for primary TKA has been quite high,the number of revision surgeries can not be ignored.Bone loss is one of the challenges confronting surgeons who perform revision TKAs as it can impair alignment accuracy and the long-term stability of the implant.Although several options are available for bone loss after TKA--cement,bone grafting,standard augments,and hinged implants--there is no single ideal option available for all patients with a severe bone defect because of the variety and severity of the defects.1 The burgeoning rapid prototyping (RP) technique,which has been used to fabricate components with complex and unique structures,may offer a novel option in these cases.Keywords:rapid prototyping; severe bone defects; knee展开更多
Revision total hip arthroplasty(THA)with massive bone loss has been a real challenge for orthopaedic surgeons.Here we describe an approach using mineralized collagen(MC)graft to reconstruct acetabulum and femur with m...Revision total hip arthroplasty(THA)with massive bone loss has been a real challenge for orthopaedic surgeons.Here we describe an approach using mineralized collagen(MC)graft to reconstruct acetabulum and femur with massive bone defects.We identified 89 patients suffering acetabular or femoral bone defects after primary THA,who required revision THA for this study.During the surgery,MC was applied to reconstruct both the acetabular and femoral defects.Harris hip score was used to evaluate hip function while radiographs were taken to estimate bone formation in the defect regions.The average follow-up period was 33.662.4 months.None of the components needed re-revised.Mean Harris hip scores were 42.563.5 before operation,75.264.0 at 10th month and 95.063.6 at the final follow-up.There were no instances of deep infection,severe venous thrombosis or nerve palsy.The present study demonstrated that MC graft can serve as a promising option for revision THA with massive bone deficiency.Meanwhile,extended follow-up is needed to further prove its long-term performance.展开更多
For large segmental bone defects,porous titanium scaffolds have some advantages,however,they lack electrical activity which hinders their further use.In this study,a barium titanate(BaTiO3)piezoelectric ceramic was us...For large segmental bone defects,porous titanium scaffolds have some advantages,however,they lack electrical activity which hinders their further use.In this study,a barium titanate(BaTiO3)piezoelectric ceramic was used to modify the surface of a porous Ti6Al4V scaffold(pTi),which was characterized by scanning electron microscopy,energy dispersive spectroscopy,X-ray photoelectron spectroscopy,and roughness and water contact angle analyses.Low intensity pulsed ultrasound(LIPUS)was applied in vitro and in vivo study.The activity of bone marrow mesenchymal stem cells,including adhesion,proliferation,and gene expression,was significantly superior in the BaTiO3/pTi,pTi+LIPUS,and BaTiO3/pTi+LIPUS groups than in the pTi group.The activity was also higher in the BaTiO3/pTi+LIPUS group than in the BaTiO3/pTi and pTi+LIPUS groups.Additionally,micro-computed tomography,the mineral apposition rate,histomorphology,and the peak pull-out load showed that these scaffold conditions significantly enhanced osteogenesis and osseointegration 6 and 12 weeks after implantation in large segmental bone defects in the radius of rabbits compared with those resulting from the pTi condition.Consequently,the improved osteogenesis and osseointegration make the BaTiO3/pTi+LIPUS a promising method to promote bone regeneration in large segmental bone defects for clinical application.展开更多
Mussel-derived nacre and pearl,which are natural composites composed CaCO3 platelets and interplatelet organic matrix,have recently gained interest due to their osteogenic potential.The crystal form of CaCO3 could be ...Mussel-derived nacre and pearl,which are natural composites composed CaCO3 platelets and interplatelet organic matrix,have recently gained interest due to their osteogenic potential.The crystal form of CaCO3 could be either aragonite or vaterite depending on the characteristics of mineralization template within pearls.So far,little attention has been paid on the different osteogenic capacities between aragonite and vaterite pearl.In the current work,aragonite or vaterite pearl powders were incorporated into poly-L-lactic acid(PLLA)scaffold as bio-functional fillers for enhanced osteogenesis.In intro results revealed that PLLA/aragonite scaffold possessed stronger stimulatory effect on SaOS-2 cell proliferation and differentiation,evidenced by the enhanced cell viability,alkaline phosphatase activity,collagen synthesis and gene expressions of osteogenic markers including osteocalcin,osteopotin and bone sialoprotein.The bone regeneration potential of various scaffolds was evaluated in vivo employing a rabbit critical-sized radial bone defect model.The X-ray and micro-CT results showed that significant bone regeneration and bridging were achieved in defects implanted with composite scaffolds,while less bone formation and non-bridging were found for pure PLLA group.Histological evaluation using Masson's trichrome and hematoxylin/eosin(H&E)staining indicated a typical endochondral bone formation process conducted at defect sites treated with composite scaffolds.Through three-point bending test,the limbs implanted with PLLA/aragonite scaffold were found to bear significantly higher bending load compared to other two groups.Together,it is suggested that aragonite pearl has superior osteogenic capacity over vaterite pearl and PLLA/aragonite scaffold can be employed as a potential bone graft for bone regeneration.展开更多
Background Repair of large bone defects remains a challenge for clinicians. The present study investigated the ability of mesenchymal stem cells (MSCs) and/or periosteum-loaded poly(lactic-co-glycolic acid) (PLGA...Background Repair of large bone defects remains a challenge for clinicians. The present study investigated the ability of mesenchymal stem cells (MSCs) and/or periosteum-loaded poly(lactic-co-glycolic acid) (PLGA) to promote new bone formation within rabbit ulnar segmental bone defects. Methods Rabbit bone marrow-derived MSCs (passage 3) were seeded onto porous PLGA scaffolds. Forty segmental bone defects, each 15 mm in length, were created in the rabbit ulna, from which periosteum was obtained. Bone defects were treated with either PLGA alone (group A), PLGA + MSCs (group B), periosteum-wrapped PLGA (group C) or periosteum-wrapped PLGA/MSCs (group D). At 6 and 12 weeks post-surgery, samples were detected by gross observation, radiological examination (X-ray and micro-CT) and histological analyses. Results Group D, comprising both periosteum and MSCs, showed better bone quality, higher X-ray scores and a greater amount of bone volume compared with the other three groups at each time point (P 〈0.05). No significant differences in radiological scores and amount of bone volume were found between groups B and C (P 〉0.05), both of which were significantly higher than group A (P 〈0.05). Conclusions Implanted MSCs combined with periosteum have a synergistic effect on segmental bone regeneration and that periosteum plays a critical role in the process. Fabrication of angiogenic and osteogenic cellular constructs or tissue-engineered periosteum will have broad applications in bone tissue engineering.展开更多
Background Calcium phosphate cement (CPC) is a favorable bone-graft substitute, with excellent biocompatibility and osteoconductivity. However, its reduced osteoinductive ability may limit the utility of CPC. To inc...Background Calcium phosphate cement (CPC) is a favorable bone-graft substitute, with excellent biocompatibility and osteoconductivity. However, its reduced osteoinductive ability may limit the utility of CPC. To increase its osteoinductive potential, this study aimed to prepare tissue-engineered CPC and evaluate its use in the repair of bone defects. The fate of transplanted seed cells in vivo was observed at the same time. Methods Tissue-engineered CPC was prepared by seeding CPC with encapsulated bone mesenchymal stem cells (BMSCs) expressing recombinant human bone morphogenetic protein-2 (rhBMP-2) and green fluorescent protein (GFP). Tissue-engineered CPC and pure CPC were implanted into rabbit femoral condyle bone defects respectively. Twelve weeks later, radiographs, morphological observations, histomorphometrical evaluations, and in vivo tracing were performed. Results The radiographs revealed better absorption and faster new bone formation for tissue-engineered CPC than pure CPC. Morphological and histomorphometrical evaluations indicated that tissue-engineered CPC separated into numerous small blocks, with active absorption and reconstruction noted, whereas the residual CPC area was larger in the group treated with pure CPC. In the tissue-engineered CPC group, in vivo tracing revealed numerous cells expressing both GFP and rhBMP-2 that were distributed in the medullar cavity and on the surface of bony trabeculae. Conclusion Tissue-engineered CPC can effectively repair bone defects, with allogenic seeded cells able to grow and differentiate in vivo after transplantation.展开更多
Background Given that three-dimensional finite element models have been successfully used to analyze biomechanics in orthopedics-related research, this study aimed to establish a finite element model of the pelvic bon...Background Given that three-dimensional finite element models have been successfully used to analyze biomechanics in orthopedics-related research, this study aimed to establish a finite element model of the pelvic bone and three-fin acetabular component and evaluate biomechanical changes in this model after implantation of a three-fin acetabular prosthesis in a superior segmental bone defect of the acetabulum.展开更多
文摘Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering applications.The use of advanced image acquisition techniques,image processing,and computer-aided design methods has enabled the precise design and additive manufacturing of anatomically correct and patient-specific implants and scaffolds.However,these sophisticated techniques can be timeconsuming,labor-intensive,and expensive.Moreover,the necessary imaging and manufacturing equipment may not be readily available when urgent treatment is needed for trauma patients.In this study,a novel design and AM methods are proposed for the development of modular and customizable scaffold blocks that can be adapted to fit the bone defect area of a patient.These modular scaffold blocks can be combined to quickly form any patient-specific scaffold directly from two-dimensional(2D)medical images when the surgeon lacks access to a 3D printer or cannot wait for lengthy 3D imaging,modeling,and 3D printing during surgery.The proposed method begins with developing a bone surface-modeling algorithm that reconstructs a model of the patient’s bone from 2D medical image measurements without the need for expensive 3D medical imaging or segmentation.This algorithm can generate both patient-specific and average bone models.Additionally,a biomimetic continuous path planning method is developed for the additive manufacturing of scaffolds,allowing porous scaffold blocks with the desired biomechanical properties to be manufactured directly from 2D data or images.The algorithms are implemented,and the designed scaffold blocks are 3D printed using an extrusion-based AM process.Guidelines and instructions are also provided to assist surgeons in assembling scaffold blocks for the self-repair of patient-specific large bone 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.
基金Sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars,Ministry of Education,China
文摘The stability parameters of implants (ITV, ISQ & PTV) according to different sizes of controlled bone defects made in implant osteotomies were analyzed and the correlation among the three kinds of implant stability parameters was tested in this study. 45 tapped screw-type dental implants were inserted in three types of implant osteotomies made in 8 fresh-frozen pig femoral bones: Typel - without coronal bone defect, Type2 - with 3 mm coronal bone defects, and Type3 - with 6 mm coronal bone defects. The insertion torque values, ISQ & PTV of implants were measured and analyzed statistically. It is concluded that the circumferential coronal bone defects statistically influence the primary stability of implants; ITV, ISQ and PTV are suitable and available to detect the peri-implant coronal bone defects in 3 mm increments, and ITV and PTV are more sensitive to coronal cortical bone loss. There was a strong correlation between ITV and ISQ.
文摘In order to evaluate the efficacy of low intensity ultrasound and tissue engineering technique to repair segmental bone defects, the rabbit models of 1.5-cm long rabbit radial segmental osteoperiosteum defects were established and randomly divided into 2 groups. All defects were implanted with the composite of calcium phosphate cement and bone mesenchymal stem cells, and ad- ditionally those in experimental group were subjected to low intensity ultrasound exposure, while those in control group to sham exposure. The animals were killed on the postoperative week 4, 8 and 12 respectively, and specimens were harvested. By using radiography and the methods of biomechanics, histomorphology and bone density detection, new bone formation and material degradation were observed. The results showed that with the prolongation of time after operation, serum alkaline phosphatase (AKP) levels in both groups were gradually increased, especially in experimental group, reached the peak at 6th week (experimental group: 1,26 mmol/L; control group: 0.58 mmol/L), suggesting the new bone formation in both two group, but the amount of new bone formation was greater and bone repairing capacity stronger in experimental group than in control group. On the 4th week in experimental group, chondrocytes differentiated into woven bone, and on the 12th week, remodeling of new lamellar bone and absorption of the composite material were observed. The mechanical strength of composite material and new born density in experimental group were significantly higher than in control group, indicating that low intensity ultrasound could not only effectively increase the formation of new bone, but also accelerate the calcification of new bone. It was concluded that low intensity ultrasound could evidently accelerate the healing of bone defects repaired by bone tissue engineering.
基金The Science and Technology Project of Henan Province (182102310487)
文摘Objective: To systematically evaluate the clinical efficacy and safety of Masquelet technology and Llizarov group technology in the treatment of infectious bone defects by meta-analysis. Methods: The computer searched China Knowledge Network (CNKI), Wanfang, VIP, Chinese Biomedical Literature Database (CBM), Pubmed, Medline, Cochrane Llibrary databases. The retrieval time was from the time of the establishment of the database to January 2020. According to the inclusion and exclusion criteria, randomized controlled trials on the treatment of infectious bone defects using Masquelet technology and Llizarov technology were collected, and the retrieved literature was independently screened, evaluated, and data extracted by two researchers, and then RevMan5.3 software was used so for meta-analysis. Results: A total of 10 RCT documents were included, with a total of 496 patients, including 242 in the Masquelet group and 254 in the Llizarov group. The results of the meta-analysis showed that: in terms of bone defect healing time, total weight bearing time, treatment cost, and complication rate, the Masquelet group was significantly different from the Llizarov group, and the Masquelet group was better than the Llizarov group (P <0.05);In terms of knee joint Lowa score and SF-36 score, Masquelet group has significant differences compared with Llizarov group, Llizarov group is better than Masquelet group (P <0.05);in excellent rate, number of operations, ankle Lowa score, infection control rate In terms of excellent rate of affected limb function, there was no significant difference between Masquelet group and Llizarov group (P> 0.05). Conclusion:Compared with Llizarov technology, Masquelet technology has obvious advantages in the treatment of infectious bone defects in terms of bone defect healing time, total weight-bearing time, treatment cost, and complication rate. In terms of scoring, it has advantages over Masquelet technology, but in terms of excellent treatment rate, number of operations, and ankle lowa score. In terms of infection control rate and excellent function of affected limbs, there was no significant difference between Masquelet technology and Llizarov technology,However, due to the low quality of the included studies and the small sample size, the exact efficacy still needs to be confirmed by higher quality RCT studies.
基金supported by the National Institutes of Health(NIH)grants(5R01NS100761,1R01NS115860)California Institute for Regenerative Medicine(CIRM)grants(CLIN1-11404,CLIN2-12129,TRAN3-13332)+2 种基金the Shriners Hospitals for Children Postdoctoral Fellowship(84705-NCA-19)research grants(85108-NCA-19,85135-NCA-21)Utilization of this Shared Resource was supported by the UC Davis Comprehensive Cancer Center Support Grant awarded by the National Cancer Institute(P30CA093373).
文摘Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone regeneration.However,current strategies lack regulation of the specific endogenous cell populations for vascularized bone regeneration,thus leading to adverse tissue formation and decreased regenerative efficiency.Here,we engineered a biomaterial to regulate endogenous cell adhesion and promote vascularized bone regeneration.The biomaterial works by presenting two synthetic ligands,LLP2A and LXW7,explicitly targeting integrinsα4β1 andαvβ3,respectively,expressed on the surfaces of the cells related to bone formation and vascularization,such as mesenchymal stem cells(MSCs),osteoblasts,endothelial progenitor cells(EPCs),and endothelial cells(ECs).In vitro,the LLP2A/LXW7 modified biomaterial improved the adhesion of MSCs,osteoblasts,EPCs,and ECs via integrinα4β1 andαvβ3,respectively.In an adult rat calvarial bone defect model,the LLP2A/LXW7 modified biomaterial enhanced bone formation and vascularization by synergistically regulating endogenous cells with osteogenic and angiogenic potentials,such as DLX5^(+)cells,osteocalcin^(+)cells,CD34^(+)/CD45-cells and CD31^(+)cells.In a fetal sheep spinal bone defect model,the LLP2A/LXW7 modified biomaterial augmented bone formation and vascularization without any adverse effects.This innovative biomaterial offers an off-the-shelf,easy-to-use,and biologically safe product suitable for vascularized bone regeneration in both fetal and adult disease environments.
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 Key R&D Program of China(2020YFA0908800)National Natural Science Foundation of China(81871376,32171365,82071927,81771853,81571674)+6 种基金Guangzhou Science and Technology Program Project(202002030104,202102080128,202201020284)Talent Research Foundation of Guangdong Second Provincial General Hospital(YN-2018-002)Youth Research Foundation of Guangdong Second Provincial General Hospital(YQ-2019-011)The science foundation of Guangdong Second Provincial General Hospital(TJGC-2021002)Natural Science Foundation of Guangdong Province(2021A1515011260,2018A030313824)Shenzhen Science and Technology Innovation Committee(JCYJ20190812171820731)Research Project of Traditional Chinese Medicine Bureau of Guangdong Provincial.
文摘Stem cell-based tissue engineering has provided a promising platform for repairing of bone defects.However,the use of exogenous bone marrow mesenchymal stem cells(BMSCs)still faces many challenges such as limited sources and potential risks.It is important to develop new approach to effectively recruit endogenous BMSCs and capture them for in situ bone regeneration.Here,we designed an acoustically responsive scaffold(ARS)and embedded it into SDF-1/BMP-2 loaded hydrogel to obtain biomimetic hydrogel scaffold complexes(BSC).The SDF-1/BMP-2 cytokines can be released on demand from the BSC implanted into the defected bone via pulsed ultrasound(p-US)irradiation at optimized acoustic parameters,recruiting the endogenous BMSCs to the bone defected or BSC site.Accompanied by the daily p-US irradiation for 14 days,the alginate hydrogel was degraded,resulting in the exposure of ARS to these recruited host stem cells.Then another set of sinusoidal continuous wave ultrasound(s-US)irradiation was applied to excite the ARS intrinsic resonance,forming highly localized acoustic field around its surface and generating enhanced acoustic trapping force,by which these recruited endogenous stem cells would be captured on the scaffold,greatly promoting them to adhesively grow for in situ bone tissue regeneration.Our study provides a novel and effective strategy for in situ bone defect repairing through acoustically manipulating endogenous BMSCs.
基金Supported by the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation,No.GZC20231088President Foundation of The Third Affiliated Hospital of Southern Medical University,China,No.YP202210.
文摘BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.
基金supported by the National Natural Science Foundation of China(No.31971271)。
文摘Bone is a complex biological tissue with a complicated hierarchical nanocomposite structure.The native microen-vironment of the bone tissue may be significantly disrupted by large physiological and pathological bone defects.Bone defects are often treated via complex surgical procedures that involve the application of autografts or al-lografts.While these grafting procedures often suffer from insufficient natural bone stock and immunorejection.Moreover,these traditional treatment methods fail to simulate a regenerative microenvironment,which plays a significant role in regeneration of bone tissue and repair of large bone defects.To this end,various biomimetic scaffolds have been devised to mimic the native microenvironment of bone and thereby to simultaneously re-pair bone defects and promote bone regeneration.We propose here a novel concept,in vivo bone regenerative microenvironment(BRM),which enables repair of large bone defects and enhances new bone tissue formation with external regulation.In this review,we mainly focus on materials and methods for fabrication of biomimetic scaffolds,as well as their therapeutic efficacy in modulating the BRM of large physiological and pathological bone defects.
基金Science and Technology Key Projects Program (No. 032050112) Natural Science Fundation (No.Q2006C08)of Shandong ProvinceHealth Department of Shandong Province Projects Program (No. 2003)
文摘Background Gene therapy has been a hot spot in repair of bone defects in recent years. This study aimed to construct a recombinant plasmid pcDNA3.1-VEGF165, and to observe the effect of vascular endothelial growth factor 165 (VEGF165) gene therapy on bone defects in rabbits. Methods Total RNA was extracted from rabbit bone tissues. VEGF165 cDNA fragment was prepared by reverse transcription and the gene was cloned by polymerase chain reaction (PCR). Plasmid pMD18-T/VEGF165 combined with pcDNA3.1 was cloned to reconstruct pcDNA3.1-VEGF165 plasmid. Thirty New Zealand white rabbits weighing (2.50±0.13)kg were used to establish models of bone defects (1 cm in length) of the bilateral radii. The bone defects were repaired with absorbable gelatin sponge. After the operation, physiological sodium chloride solution was injected into the injured site in one of the forelegs of the rabbits as the control group, and pcDNA3.1-VEGF165 plasmid (0.2 ml, 200 ng) was injected into the opposite foreleg as the experiment groups. At weeks 1, 2, 4, 6, 8, and 12 after the treatments, the bones were examined by X-ray, and the specimens of the bone defects were collected, stained with HE, and observed under a light microscope. The expression of VEGF165 mRNA was examined by real-time quantitative polymerase chain reaction (RQ-PCR). Results The pcDNA3.1-VEGF165 plasmid with a correct sequence was constructed successfully. Postoperative X-ray found no difference between the two groups at week 1. In the experiment group, callus and synostosis were observed after 2 weeks, and osteosis structure was normal at week 12; these phenomena occurred much later in the control group. In the experiment group, HE staining showed a large amount of newly formed blood vessels after 2 weeks, a number of bone trabeculae with osteoblasts proliferation at 4 weeks, and fresh bone cortex and reformed medullary cavity at 12 weeks; whereas in the control group these structures formed in later phases. The VEGF165 mRNA in the experiment group was expressed at a low level at week 1, reached the peak at weeks 3, and then decreased to a normal level after 6 weeks. Conclusions Local use of pcDNA3.1-VEGF165 plasmid at bone defects can upregulate the expression of VEGF165 and accelerate the formation of capillaries and the repair of bone defects. Angiogenesis and osteogenesis can be promoted by a combination of pcDNA3.1-VEGF165 and gelatin sponge.
文摘With the population aging and an increasing desire for a high quality of life,millions of patients who suffered knee arthropathy have undergone total knee arthroplasty (TKA).Although the success rate for primary TKA has been quite high,the number of revision surgeries can not be ignored.Bone loss is one of the challenges confronting surgeons who perform revision TKAs as it can impair alignment accuracy and the long-term stability of the implant.Although several options are available for bone loss after TKA--cement,bone grafting,standard augments,and hinged implants--there is no single ideal option available for all patients with a severe bone defect because of the variety and severity of the defects.1 The burgeoning rapid prototyping (RP) technique,which has been used to fabricate components with complex and unique structures,may offer a novel option in these cases.Keywords:rapid prototyping; severe bone defects; knee
基金This work was partly supported by National Basic Research Program(973 Program)of China(2011CB606205)‘Twelfth Five-Year’National Science and Technology Support Program(2012BAI17B02)funded by the Ministry of Science and Technology of China,and the National Natural Science Foundation of China(21371106,51402167)Shandong province science and technology development program(2013GGA10036).Conflict of interest statement.None declared.
文摘Revision total hip arthroplasty(THA)with massive bone loss has been a real challenge for orthopaedic surgeons.Here we describe an approach using mineralized collagen(MC)graft to reconstruct acetabulum and femur with massive bone defects.We identified 89 patients suffering acetabular or femoral bone defects after primary THA,who required revision THA for this study.During the surgery,MC was applied to reconstruct both the acetabular and femoral defects.Harris hip score was used to evaluate hip function while radiographs were taken to estimate bone formation in the defect regions.The average follow-up period was 33.662.4 months.None of the components needed re-revised.Mean Harris hip scores were 42.563.5 before operation,75.264.0 at 10th month and 95.063.6 at the final follow-up.There were no instances of deep infection,severe venous thrombosis or nerve palsy.The present study demonstrated that MC graft can serve as a promising option for revision THA with massive bone deficiency.Meanwhile,extended follow-up is needed to further prove its long-term performance.
基金supported by grants from the National Key Research and Development Program of China(grant number 2017YFC1104901)to Zheng Guothe National Natural Science Foundation of China(grant number 51771227)to Zheng Guo+2 种基金the Youth Development Program of Chinese People's Liberation Army(No.20QNPY069)to Bo Fanthe National Natural Science Foundation of China(No.31800812)to Bo Fanthe National Natural Science Foundation of China(grant number 51771227)to Zheng Guo.
文摘For large segmental bone defects,porous titanium scaffolds have some advantages,however,they lack electrical activity which hinders their further use.In this study,a barium titanate(BaTiO3)piezoelectric ceramic was used to modify the surface of a porous Ti6Al4V scaffold(pTi),which was characterized by scanning electron microscopy,energy dispersive spectroscopy,X-ray photoelectron spectroscopy,and roughness and water contact angle analyses.Low intensity pulsed ultrasound(LIPUS)was applied in vitro and in vivo study.The activity of bone marrow mesenchymal stem cells,including adhesion,proliferation,and gene expression,was significantly superior in the BaTiO3/pTi,pTi+LIPUS,and BaTiO3/pTi+LIPUS groups than in the pTi group.The activity was also higher in the BaTiO3/pTi+LIPUS group than in the BaTiO3/pTi and pTi+LIPUS groups.Additionally,micro-computed tomography,the mineral apposition rate,histomorphology,and the peak pull-out load showed that these scaffold conditions significantly enhanced osteogenesis and osseointegration 6 and 12 weeks after implantation in large segmental bone defects in the radius of rabbits compared with those resulting from the pTi condition.Consequently,the improved osteogenesis and osseointegration make the BaTiO3/pTi+LIPUS a promising method to promote bone regeneration in large segmental bone defects for clinical application.
基金the financial support from the China Postdoctoral Science Foundation(2018M630909 and 2019T120711).
文摘Mussel-derived nacre and pearl,which are natural composites composed CaCO3 platelets and interplatelet organic matrix,have recently gained interest due to their osteogenic potential.The crystal form of CaCO3 could be either aragonite or vaterite depending on the characteristics of mineralization template within pearls.So far,little attention has been paid on the different osteogenic capacities between aragonite and vaterite pearl.In the current work,aragonite or vaterite pearl powders were incorporated into poly-L-lactic acid(PLLA)scaffold as bio-functional fillers for enhanced osteogenesis.In intro results revealed that PLLA/aragonite scaffold possessed stronger stimulatory effect on SaOS-2 cell proliferation and differentiation,evidenced by the enhanced cell viability,alkaline phosphatase activity,collagen synthesis and gene expressions of osteogenic markers including osteocalcin,osteopotin and bone sialoprotein.The bone regeneration potential of various scaffolds was evaluated in vivo employing a rabbit critical-sized radial bone defect model.The X-ray and micro-CT results showed that significant bone regeneration and bridging were achieved in defects implanted with composite scaffolds,while less bone formation and non-bridging were found for pure PLLA group.Histological evaluation using Masson's trichrome and hematoxylin/eosin(H&E)staining indicated a typical endochondral bone formation process conducted at defect sites treated with composite scaffolds.Through three-point bending test,the limbs implanted with PLLA/aragonite scaffold were found to bear significantly higher bending load compared to other two groups.Together,it is suggested that aragonite pearl has superior osteogenic capacity over vaterite pearl and PLLA/aragonite scaffold can be employed as a potential bone graft for bone regeneration.
文摘Background Repair of large bone defects remains a challenge for clinicians. The present study investigated the ability of mesenchymal stem cells (MSCs) and/or periosteum-loaded poly(lactic-co-glycolic acid) (PLGA) to promote new bone formation within rabbit ulnar segmental bone defects. Methods Rabbit bone marrow-derived MSCs (passage 3) were seeded onto porous PLGA scaffolds. Forty segmental bone defects, each 15 mm in length, were created in the rabbit ulna, from which periosteum was obtained. Bone defects were treated with either PLGA alone (group A), PLGA + MSCs (group B), periosteum-wrapped PLGA (group C) or periosteum-wrapped PLGA/MSCs (group D). At 6 and 12 weeks post-surgery, samples were detected by gross observation, radiological examination (X-ray and micro-CT) and histological analyses. Results Group D, comprising both periosteum and MSCs, showed better bone quality, higher X-ray scores and a greater amount of bone volume compared with the other three groups at each time point (P 〈0.05). No significant differences in radiological scores and amount of bone volume were found between groups B and C (P 〉0.05), both of which were significantly higher than group A (P 〈0.05). Conclusions Implanted MSCs combined with periosteum have a synergistic effect on segmental bone regeneration and that periosteum plays a critical role in the process. Fabrication of angiogenic and osteogenic cellular constructs or tissue-engineered periosteum will have broad applications in bone tissue engineering.
基金This research was supported by grants from the National Natural Science Foundation of China (Nos. 30500516, 31000432, and 30972559).
文摘Background Calcium phosphate cement (CPC) is a favorable bone-graft substitute, with excellent biocompatibility and osteoconductivity. However, its reduced osteoinductive ability may limit the utility of CPC. To increase its osteoinductive potential, this study aimed to prepare tissue-engineered CPC and evaluate its use in the repair of bone defects. The fate of transplanted seed cells in vivo was observed at the same time. Methods Tissue-engineered CPC was prepared by seeding CPC with encapsulated bone mesenchymal stem cells (BMSCs) expressing recombinant human bone morphogenetic protein-2 (rhBMP-2) and green fluorescent protein (GFP). Tissue-engineered CPC and pure CPC were implanted into rabbit femoral condyle bone defects respectively. Twelve weeks later, radiographs, morphological observations, histomorphometrical evaluations, and in vivo tracing were performed. Results The radiographs revealed better absorption and faster new bone formation for tissue-engineered CPC than pure CPC. Morphological and histomorphometrical evaluations indicated that tissue-engineered CPC separated into numerous small blocks, with active absorption and reconstruction noted, whereas the residual CPC area was larger in the group treated with pure CPC. In the tissue-engineered CPC group, in vivo tracing revealed numerous cells expressing both GFP and rhBMP-2 that were distributed in the medullar cavity and on the surface of bony trabeculae. Conclusion Tissue-engineered CPC can effectively repair bone defects, with allogenic seeded cells able to grow and differentiate in vivo after transplantation.
文摘Background Given that three-dimensional finite element models have been successfully used to analyze biomechanics in orthopedics-related research, this study aimed to establish a finite element model of the pelvic bone and three-fin acetabular component and evaluate biomechanical changes in this model after implantation of a three-fin acetabular prosthesis in a superior segmental bone defect of the acetabulum.