Long Bone Defects Research Articles

Regeneration of a Rabbit Segmental Defect with a New Bone Therapy: Autologous Blood Coagulum with Bone Morphogenetic Protein 6 and Synthetic Ceramics.

Segmental defects of long bones are among the most challenging and debilitating conditions in clinical medicine. Osteogrow-C is a novel osteoinductive device composed of recombinant human bone morphogenetic protein 6 (rhBMP6) delivered within autologous blood coagulum (ABC) with calcium phosphate ceramics that was proven efficacious in preclinical models of spinal fusion. This study aimed to evaluate the efficacy of Osteogrow-C in comparison to that of other osteoinductive therapies in a clinically relevant segmental defect model in rabbits. Segmental defects (15 mm) of rabbit ulna were treated with Osteogrow-C containing different synthetic ceramic particles (tricalcium phosphate [TCP] and TCP/hydroxyapatite 40%/60%), Osteogrow (rhBMP6/ABC), Infuse (rhBMP2/absorbable collagen sponge), and control implants without bone morphogenetic proteins. Defect healing was evaluated by invivo x-ray scans 4, 8, and 17 weeks after the surgery, and animals were killed after 17 weeks for further radiographical and histological assessment. Evaluation of x-ray images, micro-computed tomography, and histological sections revealed that both Osteogrow-C formulations as well as Osteogrow and Infuse promoted healing of the ulnar segmental defect. However, radiographic scores were higher in animals treated with Osteogrow-C than those for the other used therapies. Moreover, evaluation of invivo x-ray scans revealed that Osteogrow-C with TCP ceramics induced the most rapid defect bridging. On the other hand, control implants (ABC/TCP and ABC/biphasic calcium phosphate) promoted limited osteogenesis without defect bridging. The findings of this study suggest that Osteogrow-C is a promising safe therapeutic solution for the treatment of large bone defects, providing relief to millions of patients suffering from this debilitating condition.

Clinical Observations of the Effectiveness of the Masquelet Induced Membrane Technique in the Treatment of Critical Long-Bone Defects of the Lower and Upper Extremities.

Background and Objectives: Successful treatment of severe trauma and fractures of the long bones with successful healing and bone union is still a significant challenge for surgeons. Unfortunately, up to 10% of long-bone fractures develop bone healing disorders. The aim of this study was to evaluate the results of treating bone defects with different etiologies in the upper and lower extremities using the induced membrane technique. Materials and Methods: We prospectively evaluated the radiological and clinical outcomes of 45 patients with severe bone defects treated with the induced membrane technique during the period from May 2021 to October 2023. The time to bone defect regeneration, size of the bone defect, and the cost of treatment were evaluated. Functional outcomes were assessed using the Disabilities of the Arm Shoulder and Hand (DASH) scale, SF-36, and the Lower Limb Functional Index (LLFI). Results: The mean follow-up time was 31 months (12-35). There were 20 patients with upper extremity bone defects and 25 with lower extremity bone defects. The mean defect length was 7.9 cm for the upper extremity (3.5-18) and 5.3 cm for the lower extremity (3-11). The mean times to achieve bone union and remodeling were 6.0 months (3-12) and 9 months (3-13) for the upper and lower limbs, respectively. Clinical evaluation at the end of treatment (achieving bone union) showed statistically significant improvements in the DASH, SF-36, and LLFI scales for pre- and postoperative outcomes. There was no statistical significance in the SF-36 clinical scale scores after surgical treatment compared to reconstructive treatment of upper and lower extremity bone defects. Results: The presented reconstructive approach to the treatment of bone defects and healing disorders and extensive analysis demonstrate the effectiveness of the induced membrane technique in a short follow-up period, with a relatively high level of patient comfort and good clinical results in the treatment of severe bone defects with particularly infectious etiologies.

Reconstruction of large post-traumatic segmental femoral defects using vascularised bone flaps: a retrospective case series

BackgroundLarge femoral defects after trauma, femoral non-unions, fractures complicated by osteomyelitis or defects after bone tumour resection present high burden and increased morbidity for patient and are challenging for reconstructive surgeons. Defects larger than 6 cm and smaller defects after failed spongioplasty are suitable for reconstruction using a free, eventually a pedicled vascularised bone flap. The free fibular flap is preferred but an iliac crest free flap or a pedicled medial femoral condyle flap can be also used. These vascularised flaps are ideal for bridging defects of long bones and can be also used as osteocutaneous or osteomuscular flaps for coverage of soft tissue defect if present. The patients and their families were informed that data will be submitted for publication and they gave their written informed consent prior to the submission. The study was approved by the institutional ethic committee.MethodsWe analysed a group of eight patients with large diaphyseal or distal metaphyseal femoral defects. A free fibular flap was used in six patients, a pedicled medial ipsilateral femoral condyle flap was used in two patients and a defect in one patient was reconstructed using an iliac crest free flap.ResultsAll flaps healed completely in all patients and no fracture of the flap was detected during the study period. In one patient, a locking plate broke and was replaced by a compression plate. At the last check-up all patients were able to step on the reconstructed limb with full weight.DiscussionAlthough our study comprises a heterogeneous group of cases, they all have been successfully treated by a similar technique, adapted in each case specifically to the needs of the patient. A major limitation parameter of reconstruction by a free vascularised flap is the size of bone defect needed to be reconstructed. In case of a bone defect longer than 6 cm and a concomitant soft tissue disruption, a vascularised double-barrel fibula is the preferred.ConclusionLarge femoral defects can be successfully reconstructed with good long-term results using suitable free or pedicled vascularised bone flaps, especially preferring the free fibular flap.

Osteoinduction and Osteoconduction Evaluation of Biodegradable Magnesium Alloy Scaffolds in Repairing Large Segmental Defects in Long Bones of Rabbit Models.

Magnesium (Mg) alloy scaffolds demonstrate promising potential for clinical applications in the repair of segmental bone defects. However, the specific mechanisms of osteoconduction and osteoinduction facilitated by these scaffolds themselves during the bone reconstruction process remain inadequately defined. This investigation systematically assesses the properties of MAO-coated Mg base implants both in vitro and in vivo. Furthermore, it elucidates the correlation between scaffold characteristics and bone regeneration in the repair of extensive long-bone defects, measuring up to 20 mm, without the use of additional bone graft materials. Electrochemical measurements and immersion tests conducted in vitro indicate that the MAO coating substantially enhances the corrosion resistance of the underlying Mg alloy. Meanwhile, the application of MAO coatings has been shown to significantly improve cytocompatibility, cellular adhesion, and osteogenic differentiation, as evidenced by the CCK-8 assays, ALP activity measurements, Western blot, and RT-qPCR in vitro. At 24 weeks postimplantation with the MAO-coated Mg alloy scaffold, the large segmental defects were effectively repaired concerning both integrity and continuity. The Micro-CT gradual replacement of old bone with new bone on the implant surface was observed by X-ray and Micro-CT. Meanwhile, the histological results indicated that the MAO-coated Mg alloy scaffold maintained a robust osteogenic response. In summary, the MAO-coated Mg alloy scaffold independently exhibits effective osteoconduction and osteoinduction, playing a significant role in bone repair function without the need for additional bone graft materials.

Design and preparation of biomimetic "Hard-soft" functional scaffold with gradient irregular pore structure for bone repair

Design and preparation of biomimetic "Hard-soft" functional scaffold with gradient irregular pore structure for bone repair

Correlative Raman spectroscopy and electron microscopy identifies glycogen rich deposits correlated with local structural defects in long bones of type IV osteogenesis imperfecta patients

Osteogenesis imperfecta (OI) is a genetic bone disease occurring in approximately 1 in 10,000 births, usually as a result of genetic mutation. OI patients suffer from increased fracture risk and - depending on the severity of the disease - deformation of the limbs, which can even lead to perinatal death. Despite extensive studies, the way in which the genetic mutation is translated into structural and compositional anomalies of the tissue is still an open question. Different observations have been reported, ranging from no structural (or chemical) differences to completely chaotic bone structure and composition. Here, we investigated bone samples from two adolescent OI-IV patients, focusing on the bone structure and chemistry in naturally occurring fractures. The exposed fracture plane allows the investigation of the structure and composition of the weakest bone plane. We do so by combining scanning electron microscopy (SEM) imaging with chemical information from Raman microscopy. The exposed fracture planes show different regions within the same tissue, displaying normal osteonal structures next to disorganized osteons and totally disordered structures, while the collagen mineralization in all cases is similar to that of a healthy bone. In addition, we also detected significant amounts of depositions of glycogen-rich, organic, globules of 250-1000nm in size. These depositions point to a role of cellular disfunction in the disorganization of the collagen in qualitative OI. Overall, our results unite multiple, sometimes contradicting views from the literature on qualitative OI.

The management of critical bone defects: outcomes of a systematic approach

BackgroundThe reconstruction of segmental long bone defects remains one of ‘The holy grails of orthopaedics’. The optimal treatment of which remains a topic of great debate. This study aimed to evaluate the outcomes following the management of critical-sized bone defects using a classification-based treatment algorithm.MethodsA retrospective review of all patients undergoing treatment for segmental diaphyseal defects of long bones at a tertiary-level limb reconstruction unit between January 2016 and December 2021, was performed. The management of the bone defect was standardised as per the classification by Ferreira and Tanwar (2020).ResultsA total of 96 patients (mean age 39.8, SD 15.2) with a minimum six months follow-up were included. Most bone defects were the result of open fractures (75/96) with 67% associated with Gustilo-Anderson IIIB injuries. There was a statistical difference in the likelihood of union between treatment strategies with more than 90% of cases undergoing acute shortening and bone transport achieving union and only 72% of cases undergoing the induced membrane technique consolidating (p = 0.049). Of those defects that consolidated, there was no difference in the time to bone union between strategies (p = 0.308) with an overall median time to union 8.33 months (95% CI 7.4 – 9.2 months). The induced membrane technique was associated with a 40% risk of sepsis.ConclusionThis study reported the outcomes of a standardised approach to the management of critical-sized bone defects. Whilst overall results were supportive of this approach, the outcomes associated with the induced membrane technique require further refinement of its indications in the management of critical-sized bone defects.Level of evidence4.

THE MANAGEMENT OF CRITICAL BONE DEFECTS: OUTCOMES OF A SYSTEMATIC APPROACH

IntroductionThe reconstruction of segmental long bone defects remains one of the holy grails of orthopaedic surgery. The optimal treatment of which remains a topic of great debate. This study aimed to evaluate the outcomes following the management of critical-sized bone defects using a classification-based treatment algorithm.Materials & MethodsA retrospective review of all patients undergoing treatment for segmental diaphyseal defects of long bones at a tertiary-level limb reconstruction unit was performed. The management of the bone defect was standardised as per the classification by Ferreira and Tanwar (2020).ResultsA total of 96 patients (mean age 39.8, SD 15.2) with a minimum six months follow-up were included. Most bone defects were the result of open fractures (75/96) with 67% associated with Gustilo-Anderson IIIB injuries. There was a statistical difference in the likelihood of union between treatment strategies with more than 90% of cases undergoing acute shortening and bone transport achieving union and only 72% of cases undergoing the induced membrane technique consolidating (p=0.049). Of those defects that consolidated, there was no difference in the time to bone union between strategies (p=0.308) with an overall median time to union 8.33 months (95% CI 7.4 — 9.2 months). The induced membrane technique was associated with a 40% risk of sepsis.ConclusionsThis study reported the outcomes of a standardised approach to the management of critical-sized bone defects. Whilst overall results were supportive of this approach, the outcomes associated with the induced membrane technique require further refinement of its indications in the management of critical-sized bone defects.

Modern Technologies for Bone Defect Replacement (Literature Review)

Information is provided regarding the materials used to replace bone defects caused by gunshot wounds. Materials and various techniques for replacing bone defects of the limbs are described. Goal. Conduct an analysis of surgical technologies and materials for the replacement of bone defects, by analyzing literary sources. Methods. In three reputable databases (PubMed, Scopus, and Web of Science), an analysis of the latest scientific studies devoted to the treatment of defects of long tubular bones in the period from 2015 to 2022 was carried out. The search was carried out using the keywords "bone defects", "autograft", "allograft", "Ilizarov method", "Masquelet method", "biocomposite materials". The results. Analysis of osteoinductive and osteoconductive properties of auto- and allografts, modern biocomposite materials. Established advantages and disadvantages. The contemporary analysis of literary sources does not provide an objective comparative assessment of the effectiveness of the treatment of bone defects according to the Masquelet and Ilizarov method due to the lack of a sufficient number of randomized studies, which is the basis for further targeted research. Conclusions. Treatment of bone tissue defects of various genesis is an urgent problem of modern orthopedics and traumatology. The wide range of treatment options is proof that no single strategy works for every patient, just as there is no perfect universal material to fill and ensure bone regeneration in the defect site. A promising direction is the search for new or a combination of known materials and methods, which are able to maximally provide compensation for these pathological conditions.

Fibula free flap for mandibular reconstruction following total en bloc resection in ameloblastoma: a case report and literature review

Background: The fibular free flap is considered the gold standard in mandibular bone reconstruction. It has a high survival rate, is well-vascularized, and fits seamlessly into long-bone defects. The purpose of this article is to describe the use of vascularized fibular free flap in mandibular reconstruction after total en bloc resection in case of ameloblastoma suspected of repeated trauma to the mandible. Case Presentation: A case report of a 26-year-old patient undergoing a mandibular reconstruction using fibula osteocutenous free flap following total en bloc resection due to ameloblastoma on mandibular symphisis region was monitored using Doppler ultrasound every 15 minutes for three to five days. Within four months of treatment, the patient had improved, and the graft was found to be viable. Conclusion: The severity and size of the affected tissue, the tumour's histological arrangement, and the consequences were the influence of whether or not ameloblastoma patients should require surgery. To determine the best course of treatment for each individual case of ameloblastoma, an accurate clinical examination and image evaluation are required.

Prevention of ankle joint deformities in children on the side of fibular graft intake for microsurgical transposition

BACKGROUND: Reconstructive operations of the musculoskeletal system in children may require the removal of a massive autograft for microsurgical bone grafting. The traditional donor site is the diaphyseal part of the fibula. In the late postoperative period, these patients may develop complications such as a valgus deformity of the ankle joint on the side of the donor fibular defect.
 AIM: To analyze the effectiveness of surgical methods for the prevention of hallux valgus of the ankle joint after free transplantation of a fragment of the fibula to replace limb-bone defects in children.
 MATERIALS AND METHODS: The treatment results of 11 patients aged 11–16 years (6 girls and 5 boys), in whom an autograft from the fibular diaphysis was used to replace defects in long tubular bones were analyzed. Two patients had a femoral defect as a result of previously transferred hematogenous osteomyelitis. A congenital false joint of the femur was found in 2 patients, bones of the lower leg in 6, and the ulna in 1. The distal fragment of the resected fibula was stabilized by an autograft from the iliac bone, in eight and three cases at the level of the diaphysis and metaphysis of the specified fragment, respectively. The size of the resected fragment in % of the total length of the fibula and the level of distal osteotomy were considered. The presence and magnitude of the proximal displacement of the fragment and the position of the ankle joint gap were evaluated at least 5 years after surgery.
 RESULTS: In this study, ≥5 years after the intervention, proximal displacement of the distal fragment of the fibula was absent in only one patient. In the remaining 10, the displacement value did not exceed 3.5 mm. Valgus deformity in the ankle joint of 5° from the initial position developed in two patients. Its progression was prevented by temporary hemiepiphysis of the distal epiphysis of the tibia using a 4.0-mm diameter spongiose screw, whereas in up to 16 months, the valgus deformity progression stopped and decreased to initial values.
 CONCLUSIONS: Fibular resection in the optimal variant should preserve the distal part of the bone as much as possible, and the stability of the ankle joint increases with synostosis of the shin bones in the distal diaphyseal section without bringing the bones closer together. When a clinically significant valgus deformity appears (5° from the initial position) with the preservation of the function of the distal growth zone of the tibia, the use of temporary transphyseal hemiepiphysiodesis of the tibia for correction is optimal.

Intercalary Prosthetic Reconstruction with Three-Dimensional-Printed Custom-Made Porous Component for Defects of Long Bones with Short Residual Bone Segments After Tumor Resection.

Intercalary reconstruction for patients with short residual bone segments remains challenging. Three-dimensional (3D)-printed custom-made porous implants are a promising technique for short-segment fixation in these patients. This study aims to evaluate the efficiency of 3D-printed custom-made porous components (3DCPCs) for short-segment fixation, focusing on prosthesis survivorship, radiographic results, and potential complications. This retrospective study involved 39 patients who underwent intercalary prosthetic reconstruction with 3DCPCs after tumor resection of the femur, tibia, or humerus from June 2015 to October 2020. Segment bone loss involved the femur (n = 15), tibia (n = 16), and humerus (n = 8), leaving 78 residual bone segments. There were 46 short segments requiring 46 3DCPCs and 32 segments with the ability to accommodate 32 off-the-shelf standard uncemented stems for prosthesis fixation. Clinical and functional outcomes were evaluated. Prosthesis-overall survivorship and prosthesis-specific survivorship were analyzed using Kaplan-Meier survival analysis. Radiographic results and modes of failure of using this technique were also examined. The mean follow-up was 41 months. The prosthesis-overall survivorship was 87.2% and 84.6% at 2 and 5 years, respectively. The prosthesis-specific survivorship was 92.1% and 89.5% at 2 and 5 years, respectively. There was not a substantial difference in prosthesis survivorship among the femur, tibia, and humerus. The average MSTS score was 26.2, ranging from 22 to 28. The radiographic evaluation results revealed excellent or good interface (38/46) in most of the 46 porous components. A total of 38 of 46 bone segments' remolding demonstrated no change. In total, seven patients (16.3%) had complications requiring further surgery. The prosthesis survivorship of using 3DCPCs for short-segment fixation is similar or better compared to other studies involving intercalary prosthetic reconstruction with short-segment fixation. Radiographic evaluation revealed good osteointegration and avoidance of stress shielding. Overall, intercalary prosthetic reconstruction with 3DCPC is a feasible modality for patients with short residual bone segments after tumor resection.

Guided bone regeneration in long-bone defect with a bilayer mineralized collagen membrane

Bone regeneration for large, critical-sized bone defects remains a clinical challenge nowadays. Guided bone regeneration (GBR) is a promising technique for the repair of multiple bone defects, which is widely used in oral and maxillofacial bone defects but is still unsatisfied in the treatment of long bone defects. Here, we successfully fabricated a bilayer mineralized collagen/collagen (MC/Col)-GBR membrane with excellent osteoinductive and barrier function by coating the MC particles prepared via in situ biomimetic mineralization process on one side of a sheet-like pure collagen layer. The aim of the present study was to investigate the physicochemical properties and biological functions of the MC/Col film, and to further evaluate its bone regeneration efficiency in large bone defect repair. Fourier-transform infrared spectra and X-ray diffraction patterns confirmed the presence of both hydroxyapatite and collagen phase in the MC/Col film, as well as the chemical interaction between them. stereo microscope, scanning electron microscopy and atomic force microscope showed the uniform distribution of MC particles in the MC/Col film, resulting in a rougher surface compared to the pure Col film. The quantitative analysis of surface contact angle, light transmittance and tensile strength demonstrated that the MC/Col film have better hydrophilicity, mechanical properties, light-barrier properties, respectively. In vitro macrophage co-culture experiments showed that the MC/Col film can effectively inhibit macrophage proliferation and fusion, reducing fibrous capsule formation. In vivo bone repair assessment of a rabbit critical segmental radial defect proved that the MC/Col film performed better than other groups in promoting bone repair and regeneration due to their unique dual osteoinductive/barrier function. These findings provided evidence that MC/Col film has a great clinical potential for effective bone defect repair.Graphic abstract

Optimization of the treatment system for victims with long-bone gunshot fractures

Background. The full-scale war with the russian federation on the territory of Ukraine revealed a number of problematic issues regarding medical and evacuation measures for victims with gunshot injuries to the extremities, requiring the search for ways to solve them and substantiate proposals for optimizing the adjusted system of treating victims. Over a 3-month period, the number of patients with gunshot wounds to the limbs and the severity of injuries increased significantly, which is primarily due to the use of weapons with high kinetic energy (Grad, Smerch MLRS systems, air bombs, including cluster munitions, artillery and tanks (large caliber)), which led to an increase in the number of patients with severe gunshot injuries. Given these features, the question arose not only regarding the training of specialists in the treatment of modern combat injuries, but also optimizing the therapeutic process, which made this topic relevant. The aim: to analyze the system of surgical treatment for victims with gunshot wounds to the extremities by optimizing the algorithm of surgical treatment at the levels of medical evacuation. Materials and methods. Statistical materials for the period from February 24 to May 2022 and ATO/JFO data for 2014–2021. Research methods: descriptive, comparative analysis, systematic approach, statistical. Based on study results, a number of debatable issues on organizing a system for the treatment of victims with gunshot wounds were identified: analysis of the distribution of patients by a type of damaging factor; optimization of triage of victims with gunshot wounds to the extremities; general characteristics of the basic principles of treatment at the hospital stage; the presence of errors in the treatment of victims with long-bone gunshot fractures. Conclusions. The widespread use of weapons with high kinetic energy during the full-scale war with the russian federation in Ukraine determined an increase in the proportion of limb lesions and the severity of these injuries. At the same time, there was an increase in the number of victims with amputated limbs, defects in long bones and polystructural trauma. Rational medical triage in the mass admission of patients with limb injuries, which we carried out, made it possible to create conditions for the full implementation of medical and diagnostic measures with the subsequent determination of priority areas.

Silicone rubber sealed channel induced self-healing of large bone defects: Where is the limit of self-healing of bone?

Large defects of long tubular bones due to severe trauma, bone tumor resection, or osteomyelitis debridement are challenging in orthopedics. Bone non-union and other complications often lead to serious consequences. At present, autologous bone graft is still the gold standard for the treatment of large bone defects. However, autologous bone graft sources are limited. Silicon rubber (SR) materials are widely used in biomedical fields, due to their safety and biocompatibility, and even shown to induce nerve regeneration. We extracted rat bone marrow mesenchymal stem cells (BMMSCs) in vitro and verified the biocompatibility of silicone rubber through cell experiments. Then we designed a rabbit radius critical sized bone defect model to verify the effect of silicone rubber sealed channel inducing bone repair in vivo. SR sealed channel could prevent the fibrous tissue from entering the fracture end and forming bone nonunion, thereby inducing self-healing of long tubular bone through endochondral osteogenesis. The hematoma tissue formed in the early stage was rich in osteogenesis and angiogenesis related proteins, and gradually turned into vascularization and endochondral osteogenesis, and finally realized bone regeneration. In summary, our study proved that SR sealed channel could prevent the fibrous tissue from entering the fracture end and induce self-healing of long tubular bone through endochondral osteogenesis. In this process, the sealed environment provided by the SR channel was key, and this might indicate that the limit of self-healing of bone exceeded the previously thought. This study investigated a new concept to induce the self-healing of large bone defects. It could avoid trauma caused by autologous bone extraction and possible rejection reactions caused by bone graft materials. Further research based on this study, including the innovation of induction materials, might invent a new type of bone inducing production, which could bring convenience to patients. We believed that this study had significant meaning for the treatment of large bone defects in clinical practice.

Fibula free flap for mandibular reconstruction following total en bloc resection in ameloblastoma: a case report and literature review

Background: The fibular free flap is considered the gold standard in mandibular bone reconstruction. It has a high survival rate, is well-vascularized, and fits seamlessly into long-bone defects. The purpose of this article is to describe the use of vascularized fibular free flap in mandibular reconstruction after total en bloc resection in case of ameloblastoma suspected of repeated trauma to the mandible. Method: A case report of a 26-year-old patient undergoing a mandibular reconstruction using fibula osteocutenous free flap following total en bloc resection due to ameloblastoma on mandibular symphisis region was monitored using Doppler ultrasound every 15 minutes for three to five days. Result: Within four months of treatment, the patient had improved, and the graft was found to be viable. Conclusion: The severity and size of the affected tissue, the tumour's histological arrangement, and the consequences were the influence of whether or not ameloblastoma patients should require surgery. To determine the best course of treatment for each individual case of ameloblastoma, an accurate clinical examination and image evaluation are required.

Bioactive Bone Substitute in a Rabbit Ulna Model: Preclinical Study.

Current therapies to effectively treat long-bone defects and extensive bone tissue loss remains limited. In this study, we created a new bone substitute by integrating advanced technologies such as structure patterning, controlled release of a bone growth factor and conjugation system for clinically effective bone regeneration. This novel bioactive bone substitute was evaluated for its safety and efficacy using a rabbit ulna model. A three dimensional bone patterned cylindrical structure with 1.5cm in length and 5mm in diameter was printed using poly(L-lactic acid)(PLLA) as a weight-bearing support and space-filling scaffold. And a bone morphogenetic protein 2 (BMP2) was employed to enhance bone regeneration, and coated to a 3D PLLA using alginate catechol and collagen to prolong the release kinetics. This novel bone substitute (BS)was evaluated for its physico-chemical and biological properties in vitro, and histological analysis and radiographical analysis such as X-ray, CT and micro-CT image analysis were performed to evaluate new bone formation in vivo. The BS possesses an ideal shape and mechanically suitable proeperties for clinical use, with an easy-to-grab and break-resistant design at both ends, 80 ± 10MPa of compression strength, and BMP2 release for two months. Histological analysis demonstrated the biocompability of BS with minimal inflammation and immune response, and X-ray, CT and micro-CT demonstrated effective new bone formation in rabbit ulna defect model. The preclinical study of a novel bioactive bone substitute has shown its safe and effective properties in an animal model suggesting its clinical potential.

GSTT1 as a Predictive Marker and Enhancer for Osteogenic Potential of Human Adipose-Derived Stromal/Stem Cells.

Adipose-derived stromal/stem cells (ASCs) have been extensively studied as cell sources for regenerative medicine for bone because of their excellent proliferative capacity and the ability to obtain a large number of cells with minimal donor morbidity. On the other hand, the differentiation potential of ASCs is generally lower than that of bone marrow-derived stromal/stem cells and varies greatly depending on donors. In this study, we mined a marker that can predict the osteogenic potential of ASC clones and also investigated the usefulness of the molecule as the enhancer of osteogenic differentiation of ASCs as well as its mechanism of action. Through RNA-seq gene analysis, we discovered that GSTT1 (Glutathione S-transferase theta-1) was the most distinguished gene marker between highly osteogenic and poorly osteogenic ASC clones. Knockdown of GSTT1 in high osteogenic ASCs by siGSTT1 treatment reduced mineralized matrix formation. On the other hand, GSTT1 overexpression by GSTT1 transfection or GSTT1 recombinant protein treatment enhanced osteogenic differentiation of low osteogenic ASCs. Metabolomic analysis confirmed significant changes of metabolites related to bone differentiation in ASCs transfected with GSTT1. A high total antioxidant capacity, low levels of cellular reactive oxygen species, and increased GSH/GSSG ratios were also detected in GSTT1-transfected ASCs. When the in vivo effect of GSTT1-transfected ASCs on bone regeneration was investigated with segmental long-bone defect model in rats, bone regeneration was significantly better after implantation of GSTT1-transfected ASCs compared with that of control vector-transfected ASCs. In conclusion, GSTT1 can be a useful marker to screen the highly osteogenic ASC clones and also a therapeutic factor to enhance the osteogenic differentiation of poorly osteogenic ASC clones. © 2023 American Society for Bone and Mineral Research (ASBMR).

Current Management of Diaphyseal Long Bone Defects-A Multidisciplinary and International Perspective.

The treatment of defects of the long bones remains one of the biggest challenges in trauma and orthopedic surgery. The treatment path is usually very wearing for the patient, the patient's environment and the treating physician. The clinical or regional circumstances, the defect etiology and the patient´s condition and mental status define the treatment path chosen by the treating surgeon. Depending on the patient´s demands, the bony reconstruction has to be taken into consideration at a defect size of 2-3 cm, especially in the lower limbs. Below this defect size, acute shortening or bone grafting is usually preferred. A thorough assessment of the patient´s condition including comorbidities in a multidisciplinary manner and her or his personal demands must be taken into consideration. Several techniques are available to restore continuity of the long bone. In general, these techniques can be divided into repair techniques and reconstructive techniques. The aim of the repair techniques is anatomical restoration of the bone with differentiation of the cortex and marrow. Currently, classic, hybrid or all-internal distraction devices are technical options. However, they are all based on distraction osteogenesis. Reconstructive techniques restore long-bone continuity by replacing the defect zone with autologous bone, e.g., with a vascularized bone graft or with the technique described by Masquelet. Allografts for defect reconstruction in long bones might also be described as possible options. Due to limited access to allografts in many countries and the authors' opinion that allografts result in poorer outcomes, this review focuses on autologous techniques and gives an internationally aligned overview of the current concepts in repair or reconstruction techniques of segmental long-bone defects.

3D-Printed Osteoinductive Polymeric Scaffolds with Optimized Architecture to Repair a Sheep Metatarsal Critical-Size Bone Defect.

The reconstruction of critical-size bone defects in long bones remains a challenge for clinicians. A new osteoinductive medical device is developed here for long bone repair by combining a 3D-printed architectured cylindrical scaffold made of clinical-grade polylactic acid (PLA) with a polyelectrolyte film coating delivering the osteogenic bone morphogenetic protein 2 (BMP-2). This film-coated scaffold is used to repair a sheep metatarsal 25-mm long critical-size bone defect. In vitro and in vivo biocompatibility of the film-coated PLA material is proved according to ISO standards. Scaffold geometry is found to influence BMP-2 incorporation. Bone regeneration is followed using X-ray scans, µCT scans, and histology. It is shown that scaffold internal geometry, notably pore shape, influenced bone regeneration, which is homogenous longitudinally. Scaffolds with cubic pores of ≈870µm and a low BMP-2 dose of ≈120µgcm-3 induce the best bone regeneration without any adverse effects. The visual score given by clinicians during animal follow-up is found to be an easy way to predict bone regeneration. This work opens perspectives for a clinical application in personalized bone regeneration.