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.

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.

Gene expression analysis of cytokines and MMPs in melatonin and rhBMP-2 enhanced bone remodeling

BACKGROUND In the medical and dental fields,there is a need for studies of new therapeutic approaches for the treatment of bone defects that cause extensive bone loss.Melatonin may be an important endogenous biological factor for bone remodeling,and growth factors may enhance the repair process.AIM To evaluate the gene expression of cytokines(IL-1β,IL-6,IL-10 and TNF-α),markers of osteoclastogenesis(RANK,RANKL and OPG)and MMPs(MMP-1,MMP-2,MMP-8 and MMP-13)from the treatment of melatonin associated with an osteogenic membrane and rhBMP-2 on the recovery of a bone injury.METHODS Sixty-four rats were used and divided into 9 experimental groups and were formed according to the treatment carried out in the region of the bone lesion,which varied between the combination of 1,10 and 100μmol/L of melatonin.Gene Expression analysis was performed using real time-PCR by reading the concentration of total RNA and reverse transcription.RESULTS There were differences between groups when compared with clot or scaffold control,and improvement with a higher concentration of melatonin or rhBMP-2.The combination melatonin(1μg)with 5μg of rhBMP-2,using the guided bone regeneration technique,demonstrated some effects,albeit mild,on bone repair of critical bone defects.CONCLUSION This indicates that the approach for administering these substances needs to be reassessed,with the goal of ensuring their direct application to the affected area.Therefore,future research must be carried out,seeking to produce materials with these ideal characteristics.

Ilizarov technique for treatment of a giant aneurysmal bone cyst at the distal femur:A case report

BACKGROUND Aneurysmal bone cyst(ABC)is a benign cystic of unknown etiology,characterized by multiple chambers and a high recurrence rate.Current treatment options include vascular embolization,surgical excision,curettage with cavity filling,sclerosing agent injection into the cavity,radiotherapy,and systemic drug therapy.Among these,surgical excision and curettage are the preferred treatment modalities.However,when the cyst reaches a large size,extensive removal of diseased tissue during surgery can hinder bone healing.In our department,we treated a case of a large ABC at the distal end of the femur in a child using the Ilizarov technique.The tumor was completely excised,and reconstruction was achieved through autologous femoral bone transfer.The follow-up at two years post-surgery indicated good results without tumor recurrence,and the growth and development of the child were essentially unaffected.CASE SUMMARY An 11-year-old boy was presented with an accidental fracture of his right leg.Despite having been examined at other hospitals,he had not received treatment.Given the potential for significant bone defects and the difficulty of the surgery,our doctors opted to use the Ilizarov technique to minimize harm to the patient.Upon admission,the patient underwent a needle biopsy and complete tumor resection-the Ilizarov technique assisted in the transport and reconstruction of the autologous femoral bone.Postoperatively,the patient exhibited regular followups,during which bone transport was gradually performed,and the external fixation frame was removed on time.Follow-up X-rays of the right lower limb displayed no tumor recurrence,with a normal appearance.Bone formation at the cutting site was satisfactory,and the union of the bone ends indicated good healing.After two years of follow-up,the patient had essentially returned to normal.CONCLUSION We successfully applied the Ilizarov technique to treat ABC,reducing the financial burden of patients and the pain of multiple surgeries.In cases where significant bone defects occur,the Ilizarov technique has demonstrated satisfactory therapeutic outcomes.

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.

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 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.

Bone Regeneration Enhanced by Antigen-Extracted Xenogeneic Cancellous Bone Graft with rhBMP-2 in Rabbits Mandibular Defect Repair

The effects of large piece xenogeneic bone which was separated from healthy pigs as a scaffold on repair of mandibular defect was investigated and the applicability of antigen-extracted xenogeneic cancellous bone (AXCB) soaked with rhBMP-2 in bone defect repair was assessed. Mandibular defects were created in 48 New Zealand Rabbits, and then randomly divided into 4 groups, which was grafted in the mandibular defects with AXCB, AXCB soaked with rhBMP-2, autograft bone, or blank. Equal number of animals from each group was classified into three time points (4, 8, and 12 weeks) after operation for gross pathological observation, hematoxylin and eosin (H & E) staining, radiographic examination, and bone density measurement. H & E staining revealed that the area percentage of bone regeneration in the group of AXCB/rhBMP-2 graft was 27.72 ± 4.68, 53.90 ± 21.92, and 77.35 ± 9.83 when at 4, 8, and 12 weeks, which was better than that of auto bone graft, prompting that the group of AXCB/rhBMP-2 graft had commendable osteogenic effect. And comparing with the AXCB without rhBMP-2, of which the area percentage of bone regeneration was only 14.03 ± 5.02, 28.49 ± 11.35, and 53.90 ± 21.92, the osteogenic effect of AXCB/rhBMP-2 graft was demonstrated to be much better. In the group of AXCB/rhBMP-2 graft, the area percentage of bone regeneration increased, and the implanted materials were gradually degraded and replaced by autogenous bone regeneration over time. We concluded that antigen-extracted xenogeneic cancellous bone (AXCB) graft soaked with rhBMP-2 had shown excellent osteogenic effect in repair of bone defects, with good biocompability.

Biodegradable materials for bone defect repair

Compared with non-degradable materials,biodegradable biomaterials play an increasingly important role in the repairing of severe bone defects,and have attracted extensive attention from researchers.In the treatment of bone defects,scaffolds made of biodegradable materials can provide a crawling bridge for new bone tissue in the gap and a platform for cells and growth factors to play a physiological role,which will eventually be degraded and absorbed in the body and be replaced by the new bone tissue.Traditional biodegradable materials include polymers,ceramics and metals,which have been used in bone defect repairing for many years.Although these materials have more or fewer shortcomings,they are still the cornerstone of our development of a new generation of degradable materials.With the rapid development of modern science and technology,in the 21 st century,more and more kinds of new biodegradable materials emerge in endlessly,such as new intelligent micro-nano materials and cell-based products.At the same time,there are many new fabrication technologies of improving biodegradable materials,such as modular fabrication,3 D and 4 D printing,interface reinforcement and nanotechnology.This review will introduce various kinds of biodegradable materials commonly used in bone defect repairing,especially the newly emerging materials and their fabrication technology in recent years,and look forward to the future research direction,hoping to provide researchers in the field with some inspiration and reference.

Experimental Study on Low Intensity Ultrasound and Tissue Engineering to Repair Segmental Bone Defects

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.

Bovine Calcined Bone for the Repair of Radial Defect in a Rabbit Model

In order to investigate the bovine calcined bone's ability of repairing segmental bone defect and seek a new artificial bone substitute material, the bovine calcined bone (450℃,32 h) was implanted into the 10 mm middle radial defect of rabbits with tricalcium phosphate ceramics as the control. By using the methods of histology, radiology and biomechanics their osteogenic ability were measured. It was found that the bovine calcined bone's ability of repairing bone defect was better than that of tricalcium phosphate ceramics. The histological Nilsson′s scores at 3rd, 5th, 9th week after operation were significantly increased ( P <0.01). At 12th week after operation the bending strength of radius in experimental group was much higher than that of control group and turned normal. It was suggested that bovine calcined bone is an ideal artificial bone substitute material with good ability of repairing segmental bone defect and some degree of mechanical strength.

One-Stage Repair and Reconstruction of Craniomaxillofacial Bone Defects

Objective: Severe craniomaxillofacial injuries and craniomaxillofacial tumors can lead to craniomaxillofacial bone defects and deformities. Seriously affect the patients’ appearance and quality of life. So one-stage repair and reconstruction of craniomaxillofacial bone defects is of great significance. The current study summarizes the clinical experience of one-stage repair and reconstruction of craniomaxillofacial bone defects. Material and Methods: Data in one-stage repair and reconstruction of?craniomaxillofacial bone defects performed on 13 patients were retrospectively analyzed out of 34 patients with?craniomaxillofacial injuries or tumors who received treatment at the outpatient department between January 2002 and March 2011. Surgical indications and approaches were explored after two typical cases were detected. Results: One-stage repair and reconstruction of bone defects was suitable for patients with craniomaxillofacial injuries and excised craniomaxillofacial benign tumors. Adjacent autogenous bones and artificial materials (such as titanium plates, titanium mesh, and so on) work well for the repair of the craniomaxillofacial bone frame and restoration of facial features. Conclusions: Surgical indications should be strictly selected in one-stage repair and reconstruction of craniomaxillofacial bone defects and deformities. Furthermore, the adoption of autogenous bones and artificial materials is a good choice in restoring the craniofacial features.

Role of transforming growth factor P and bone morphogenetic protein composite on repair of bone defects

Objective: To study the effect of transforming growth factor β/bone morphogenetic protein (TGFβ/BMP) composite on healing of large segmental bone defects and the interaction between TGF-β and BMP.Methods: A 1. 5-centimeter segmental defect was created in the mid-upper part of the radial shaft of adultrabbit. The defects were filled with implant of TGF-β/carrier, BMP/carrier and TGF-a/BMP/carrier, respectively. Purified bovine TGF-β 120 μg and BMP 12 mg were used in the composite. The defects were examined radiographically and histologically at 4, 8. 12 and 16 weeks post-operation (PO). Results: In groupof TGF-β/carrier, the defect areas were bridged at 4 weeks PO, with material of uniform radiodensity. Conices of the cut ends were obscured by the new bone. By 16 weeks PO, the defects were bridged by uniformnew bone and the cut ends of cortex could not be seen in all groups. In group of BMP/carrier, the defectswere filled with more irregular woven callus in comparison with the other two groups. The TGF-β/BMP--implanted defect sites in animals killed at 16 weeks PO showed histologically new larnellar and woven bone,formed in continuity with the cut ends of the cortex. The medullar cavity was recanalized and contained marrow elements with normal appearance. ConClUsion: These data demonstrate the synergistic action betweenTGF-β and BMP in the process of bone healing, and the better effect of TGF-β/BMP composite than that ofsingle TGF-β or BMP on bone repair.

Skeletal Blood Flow in Bone Repair and Maintenance

Bone is a highly vascularized tissue, although this aspect of bone is often overlooked. In this article, the importance of blood flow in bone repair and regeneration will be reviewed. First, the skeletal vascular anato- my, with an emphasis on long bones, the distinct mechanisms for vascularizing bone tissue, and methods for remodeling existing vasculature are discussed. Next, techniques for quantifying bone blood flow are briefly summarized. Finally, the body of experimental work that demonstrates the role of bone blood flow in fracture healing, distraction osteogenesis, osteoporosis, disuse osteopenia, and bone grafting is examined. These results illustrate that adequate bone blood flow is an important clinical consideration, particularly during bone regeneration and in at-risk patient groups.

Bone marrow mesenchymal stem cells repair spinal cord ischemia/reperfusion injury by promoting axonal growth and anti-autophagy

Bone marrow mesenchymal stem cells can differentiate into neurons and astrocytes after trans- plantation in the spinal cord of rats with ischemia/reperfusion injury. Although bone marrow mesenchymal stem cells are known to protect against spinal cord ischemia/reperfusion injury through anti-apoptotic effects, the precise mechanisms remain unclear. In the present study, bone marrow mesenchymal stem cells were cultured and proliferated, then transplanted into rats with ischemia/reperfusion injury via retro-orbital injection. Immunohistochemistry and immunofluorescence with subsequent quantification revealed that the expression of the axonal regeneration marker, growth associated protein-43, and the neuronal marker, microtubule-as- sociated protein 2, significantly increased in rats with bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Fur- thermore, the expression of the autophagy marker, microtubule-associated protein light chain 3B, and Beclin 1, was significantly reduced in rats with the bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Western blot analysis showed that the expression of growth associated protein-43 and neuro- filament-H increased but light chain 3B and Beclin 1 decreased in rats with the bone marrow mesenchymal stem cell transplantation. Our results therefore suggest that bone marrow mes- enchymal stem cell transplantation promotes neurite growth and regeneration and prevents autophagy. These responses may likely be mechanisms underlying the protective effect of bone marrow mesenchymal stem cells against spinal cord ischemia/reperfusion injury.

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.

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.