Customized scaffolds for large bone defects using 3D‑printed modular blocks from 2D‑medical images

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.

Clinical Efficacy of GBR Technique Combined with Temporary Bridgework-Guided Gingival Contouring in Treating Upper Anterior Tooth Loss with Labial Bone Defects

Objective:To investigate the clinical effect of the guided bone regeneration(GBR)technique combined with temporary bridgework-guided gingival contouring in treating upper anterior tooth loss with labial bone defects.Methods:From July 2023 to April 2024,80 patients with upper anterior tooth loss and labial bone defects were admitted to the hospital and selected as evaluation samples.They were divided into an observation group(n=40)and a control group(n=40)using a numerical table lottery scheme.The control group received treatment with the GBR technique,while the observation group received treatment with the GBR technique combined with temporary bridges to guide gingival contouring.The two groups were compared in terms of clinical red aesthetic scores(PES),labial alveolar bone density,labial bone wall thickness,gingival papillae,gingival margin levels,and patient satisfaction.Results:The PES scores of patients in the observation group were higher than those in the control group after surgery(P<0.05).The bone density of the labial alveolar bone and the thickness of the labial bone wall in the observation group were higher than those in the control group.The levels of gingival papillae and gingival margins were lower in the observation group after surgery(P<0.05).Additionally,patient satisfaction in the observation group was higher than in the control group(P<0.05).Conclusion:The GBR technique combined with temporary bridge-guided gingival contouring for treating upper anterior tooth loss with labial bone defects can improve the aesthetic effect of gingival soft tissue,increase alveolar bone density and the thickness of the labial bone wall,and enhance patient satisfaction.This approach is suitable for widespread application in healthcare institutions.

Systematic review on the use of autologous matrix-induced chondrogenesis for the repair of articular cartilage defects in patients

AIM To systematically review the results of studies looking at autologous matrix-induced chondrogenesis(AMIC) in humans. METHODS A literature search was performed, adhering to the PRISMA guidelines, to review any studies using such techniques in humans. Our initial search retrieved 297 articles listed on MEDLINE, Google Scholar, CINHal and EMBASE. From these studies, 15 studies meeting the eligibility criteria were selected and formed the basis of our systematic review.RESULTS The study designs, surgical techniques and outcome measures varied between the studies. Although all studies reported improvements in patient outcome measures, this was not necessarily correlated with magnetic resonance imaging findings. Although there were many additional procedures performed, when AMIC was performed in isolation, the results tended to peak at 24 mo before declining. CONCLUSION Although short-term studies suggest improved patient reported outcomes with a variety of scaffolds, surgical techniques and rehabilitation regimes, the literature remains equivocal on whether the defect size and location, and patient factors affect the outcome. Patientbenefit appears to be maintained in the short-tomedium term but more high level studies with extensive and robust validated outcome measures should be conducted to evaluate the medium-and long-term effect of the AMIC procedure.

Repair of articular cartilage defects in minipigs by microfracture surgery and BMSCs transplantation

Objective:To investigate the feasibility of minimal invasive repair of cartilage defect by arthroscope-aided microfracture surgery and autologous transplantation of mesenchymal stem cells. Methods: Bone marrow of minipigs was taken out and the bone marrow derived mesenchymal stem cells (BMSCs) were isolated and cultured to passage 3. Then 6 minipigs were randomly divided into 2 groups with 6 knees in each group. After the articular cartilage defect was induced in each knee, the left defect received microfracture surgery and was injected with 2.5 ml BMSCs cells at a concentration of 3×107 cells/ml into the articular cavity; while right knee got single microfracture or served as blank control group. The animals were killed at 8 or 16 weeks, and the repair tissue was histologically and immunohistochemically examined for the presence of type Ⅱ collagen and glycosaminoglycans (GAGs) at 8 and 16 weeks. Results: Eight weeks after the surgery, the overlying articular surface of the cartilage defect showed normal color and integrated to adjacent cartilage. And 16 weeks after surgery, hyaline cartilage was observed at the repairing tissues and immunostaining indicated the diffuse presence of this type Ⅱ collagen and GAGs throughout the repair cartilage in the treated defects. Single microfracture group had the repairing of fibrocartilage, while during the treatment, the defects of blank group were covered with fewer fiber tissues, and no blood capillary growth or any immunological rejection was observed. Conclusion: Microfracture technique and BMSCs transplantation to repair cartilage defect is characterized with minimal invasion and easy operation, and it will greatly promote the regeneration repair of articular cartilage defect.

Repair effect of articular cartilage defects by nitric oxide synthase inhibitor

Objective To discuss repairing effects of articular cartilage defects by nitric oxide synthase inhibitor (S methylisothiourea, SMT), and explore the role of nitric oxide in cartilage repair. Methods Full-thickness defects of cartilage were created in the intercondylar trochlear groove of femur of thirty-six adult New Zealand white rabbits, and were divided into three gorups. Twenty-four defects were untreated as the control, twenty-four were filled with fibrin glue and impregnated with rhBMP AS rhBMP group, the rest twenty-four were filled with fibrin glue and impregnated with rhBMP, and hypodermic injection with SMT as SMT group. The animals were sacrified at sixteen weeks postoperatively, and the gross appearance of the defect was estimated. The repair tissue was examined histologically and was evaluated according to the grading scale of histology. The amount of released NO and the activities of nitric oxide synthase(NOS) were examined by chemical colorimetry. The distribution of type-Ⅰ , Ⅱ

Use of bone morphogenetic proteins in mesenchymal stemcell stimulation of cartilage and bone repair

The extracellular matrix-associated bone morphogenetic proteins(BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed in many preclinical and clinical studies exploring their chondrogenic or osteoinductive potential in several animal model defects and in human diseases. During years of research in particular two BMPs, BMP2 and BMP7 have gained the podium for their use in the treatment of various cartilage and bone defects. In particular they have been recently approved for employment in non-union fractures as adjunct therapies. On the other hand, thanks to their potentialities in biomedical applications, there is a growing interest in studying the biology of mesenchymal stem cell(MSC), the rules underneath their differentiation abilities, and to test their true abilities in tissue engineering. In fact, the specific differentiation of MSCs into targeted celltype lineages for transplantation is a primary goal of the regenerative medicine. This review provides an overview on the current knowledge of BMP roles and signaling in MSC biology and differentiation capacities. In particular the article focuses on the potential clinical use of BMPs and MSCs concomitantly, in cartilage and bone tissue repair.

Comparative study of chitosan/fibroin–hydroxyapatite and collagen membranes for guided bone regeneration in rat calvarial defects: micro-computed tomography analysis

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.

Establishing proof of concept:Platelet-rich plasma and bone marrow aspirate concentrate may improve cartilage repair following surgical treatment for osteochondral lesions of the talus

Osteochondral lesions of the talus are common injuries in the athletic patient. They present a challenging clinical problem as cartilage has a poor potential for healing. Current surgical treatments consist of reparative(microfracture) or replacement(autologous osteochondral graft) strategies and demonstrate good clinical outcomes at the short and medium term follow-up. Radiological findings and second-look arthroscopy however, indicate possible poor cartilage repair with evidence of fibrous infill and fissuring of the regenerative tissue following microfracture. Longer-term follow-up echoes these findings as it demonstrates a decline in clinical outcome. The nature of the cartilage repair that occurs for an osteochondral graft to become integrated with the native surround tissue is also of concern. Studies have shown evidence of poor cartilage integration,with chondrocyte death at the periphery of the graft, possibly causing cyst formation due to synovial fluid ingress. Biological adjuncts, in the form of platelet-rich plasma(PRP) and bone marrow aspirate concentrate(BMAC), have been investigated with regard to their potential in improving cartilage repair in both in vitro and in vitro settings. The in vitro literature indicates that these biological adjuncts may increase chondrocyte proliferation as well as synthetic capability, while limiting the catabolic effects of an inflammatory joint environment. These findings have been extrapolated to in vitro animal models, with results showing that both PRP and BMAC improve cartilage repair. The basic science literature therefore establishes the proof of concept that biological adjuncts may improve cartilage repair when used in conjunction with reparative and replacement treatment strategies for osteochondral lesions of the talus.

Study on the Microstructure of Human Articular Cartilage/Bone Interface

For improving the theory of gradient microstructure of cartilage/bone interface, human distal femurs were studied. Scanning Electron Microscope （SEM）, histological sections and MicroCT were used to observe, measure and model the micro- structure of cartilage/bone interface. The results showed that the cartilage/bone interface is in a hierarchical structure which is composed of four different tissue layers. The interlocking of hyaline cartilage and calcified cartilage and that of calcified car- tilage and subchondral bone are in the manner of＂protrusion-pore＂ with average diameter of 17.0 gm and 34.1 lam respectively. In addition, the cancellous bone under the cartilage is also formed by four layer hierarchical structure, and the adjacent layers are connected by bone trabecula in the shape of H, I and Y, forming a complex interwoven network structure. Finally, the simplified structure model of the cartilage/bone interface was proposed according to the natural articular cartilage/bone interface. The simplified model is a 4-layer gradient biomimetic structure, which corresponds to four different tissues of natural cartilage/bone interface. The results of this work would be beneficial to the design of bionic scaffold for the tissue engineering of articular cartilage/bone.

Effects of Structural Changes in Subchondral Bone on Articular Cartilage in a Beagle Dog Model

Objective Using MR T2-mapping and histopathologic score for articular cartilage to evaluate the effect of structural changes in subchondral bone on articular cartilage. Methods Twenty-four male Beagle dogs were randomly divided into a subchondral bone defect group （n = 12） and a bone cement group （n = 12）. Models of subchondral bone defectin the medial tibial plateau and subchondral bone filled with bone cement were constructed. In all dogs, the left knee joint was used as the experimental sideand the right knee as the sham side. The T2 value for articular cartilage at the medial tibial plateau was measured at postoperative weeks 4, 8, 16, and 24. The articular cartilage specimens were stained with hematoxylin and eosin, and evaluated using the Mankin score. Results There was a statistically significant difference （P 〈 0.05） in Mankin score between the bone defect group and the cement group at postoperative weeks 16 and 24. There was a statistically significant difference in the T2 values between the bone defect group and its sham group （P 〈 0.05） from week 8, and between the cement group and its sham group （P 〈 0.05） from week 16. There was significant difference in T2 values between the two experimental groups at postoperative week 24 （P 〈 0.01）. The T2 value for articular cartilage was positively correlated with the Mankin score （ρ = 0.758, P 〈 0.01）. Conclusion Structural changes in subchondral bone can lead to degeneration of the adjacent articular cartilage. Defects in subchondral bone cause more severe degeneration of cartilage than subchondral bone filled with cement. The T2 value for articular cartilage increases with the extent of degeneration. MR T2-mapping images and the T2 value for articular cartilage can indicate earlycartilage degeneration.

Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects:biomechanics and validation of mathematical models

We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects.To test this,we established rabbit models of 30 mm sciatic nerve defects,and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells.We compared the tensile properties,electrophysiological function and morphology of the damaged nerve in each group.Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone,and produced similar results to those observed with the autograft.These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects.

Role of the Ilizarov non-free bone plasty in the management of long bone defects and nonunion: Problems solved and unsolved

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.

Icariin accelerates bone regeneration by inducing osteogenesisangiogenesis coupling in rats with type 1 diabetes mellitus

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.

Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate: an in vivo microcomputed tomographic and histologic e

The aim of the present real time in vivo micro-computed tomography （pCT） and histologic experiment was to assess the efficacy of guided bone regeneration （GBR） around standardized calvarial critical size defects （CSD） using bone marrow-derived mesenchymal stem cells （BMSCs）, and collagen membrane （CM） with and without tricalcium phosphate （TCP） graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD （diameter 4.6 mm） were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone （NFB） and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo pCT. At the lOth week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups I and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical ＂lock＂ between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adiunct BMSC therapy.

In Vitro Targeted Magnetic Delivery and Tracking of Superparamagnetic Iron Oxide Particles Labeled Stem Cells for Articular Cartilage Defect Repair

To assess a novel cell manipulation technique of tissue engineering with respect to its ability to augment superparamagnetic iron oxide particles （SPIO） labeled mesenchymal stem cells （MSCs） density at a localized cartilage defect site in an in vitro phantom by applying magnetic force. Meanwhile, non-invasive imaging techniques were use to track SPIO-labeled MSCs by magnetic resonance imaging （MRI）. Human bone marrow MSCs were cultured and labeled with SPIO. Fresh degenerated human osteochondral fragments were obtained during total knee arthroplasty and a cartilage defect was created at the center. Then, the osteochondral fragments were attached to the sidewalls of culture flasks filled with phosphate-buffered saline （PBS） to mimic the human joint cavity. The SPIO-labeled MSCs were injected into the culture flasks in the presence of a 0.57 Tesla （T） magnetic force. Before and 90 min after cell targeting, the specimens underwent T2-weighted turbo spin-echo （SET2WI） sequence of 3.0 T MRI. MRI results were compared with histological findings. Macroscopic observation showed that SPIO-labeled MSCs were steered to the target region of cartilage defect. MRI revealed significant changes in signal intensity （P0.01）. HE staining exibited that a great number of MSCs formed a three-dimensional （3D） cell ＂sheet＂ structure at the chondral defect site. It was concluded that 0.57 T magnetic force permits spatial delivery of magnetically labeled MSCs to the target region in vitro. High-field MRI can serve as an very sensitive non-invasive technique for the visualization of SPIO-labeled MSCs.

Experimental study of natural hydroxyapatite/chitosan composite on reconstructing bone defects

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.

Early therapeutic effect of platelet-rich fibrin combined with allogeneic bone marrow-derived stem cells on rats’ critical-sized mandibular defects

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.

ROLE OF TRANSFORMING GROWTH FACTOR β(TGF-β)IN REPAIRING OF BONE DEFECTS

TGF-β is a multifunctional cytokine that regulates many aspects of cellular function, including periosteal mesenchymal cell proliferation, differentiation. This experiment is to study its effects on bone defect repair. A rabbit radial bone defect model was used to evaluate the effect of TGF-β, which was extracted and purified from bovine blood platelets, on the healing of a large segmental osteoperiosteal defect. A 1. 5-centimeter segmental defect was created in the mid-upper part of the radial shaft of adult rabbits. The defect was filled with implant containing TGF-β that consisted of carrier and bovine TGF-β. Limbs served as controls received carrier alone. The defectswere examined radiographically and histologically at 4, 8,12 , 16 and 20 weeks after implantation. The results showed that in TGF-β implant group . the defect areas at 12 weeks post operation were bridged by uniform new bone and the cut ends of cortex could not be seen;while in control group, the defects remained clear. Only a small amount of new bone formed as a cap on the cut bone ends. In the experimental group, new lamellar and woven bone formed in continuity with the cut ends of the cortex. An early medullar canal appears to be forming and contained normal-appearancing marrow elements; while the control group displayed entirely fibrous tissue within the defect site. Remnants of the cancellous bone carrier were observed in the control specimen. These data demonstrate that exogenous TGF-β initiate osteogenesis and stimulate the bone defects repair in animal model.

Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients

Type 2 diabetes （T2D） is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis （OA）. Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic （n---70） and diabetes （n = 51） groups. Tibial plateaus were also collected from cadaver donors （n = 20） and used as controls. Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase （TRAP）, osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International （OARSI） scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP~ osteoclasts and lower number of Osterix~ osteoprogenitors and Osteocalcin~ osteoblasts. T2D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2D-associated knee OA.

Masquelet technique in military practice:specificities and future directions for combat-related bone defect reconstruction

Because of its simplicity,reliability,and replicability,the Masquelet induced membrane technique(IMT)has become one of the preferred methods for critical bone defect reconstruction in extremities.Although it is now used worldwide,few studies have been published about IMT in military practice.Bone reconstruction is particularly challenging in this context of care due to extensive soft-tissue injury,early wound infection,and even delayed management in austere conditions.Based on our clinical expertise,recent research,and a literature analysis,this narrative review provides an overview of the IMT application to combat-related bone defects.It presents technical specificities and future developments aiming to optimize IMT outcomes,including for the management of massive multi-tissue defects or bone reconstruction performed in the field with limited resources.