Does zinc oxide nanoparticles potentiate the regenerative effect of platelet-rich fibrin in healing of critical bone defect in rabbits?

BACKGROUND: Many encouraging studies confirmed the ability of Zinc Oxide Nanoparticles (ZnONPs) in accelerating bone growth and mineralization. The use of Platelet Rich-Fibrin (PRF) as a sole filling material for large segmental bone defects remains questionable. The objectives are to investigate the regenerative efficacy of autologous Platelet Rich-Fibrin (PRF) and Zinc Oxide Nanoparticles (ZnONPs) in repairing large segmental bone ulnar defects in a randomized controlled study in rabbits using computed tomographic interpretations. A 12 mm critical size defect was surgically induced in the ulna of 30 rabbits (n = 10/ group). In the control group, the defect was left empty. In the PRF group, the defect is filled with PRF. In the PRF/ZnONPs group, the defect is filled with PRF that was inoculated with 0.1 ml of 0.2% ZnONPs. Radiologic healing capacity was evaluated at the first, second, and third postoperative months. RESULTS: Statistical analysis showed significant differences in the radiologic healing scores between the groups (P = 0.000-0.0001) at all-time points (P = 0.000-0.047) during the study. CONCLUSION: Rabbits in the PRF/ZnONPs group showed the highest appreciable bone quality and quantity followed by the PRF group with high quantity but low bone quality meanwhile, rabbits in the control group showed minimal quantity but medium bone quality. Interestingly, the addition of ZnONPs to PRF can accelerate the healing of ulnar critical-size defects in rabbits.

Vascular Supply and Bone Marrow Concentrate for the Improvement of Allograft in Bone Defects: A Comparative In Vivo Study.

BACKGROUND: Surgical repair of critical-sized bone defects still remains a big challenge in orthopedic surgery. Biological enhancement, such as growth factors or cells, can stimulate a better outcome in bone regeneration driven by well-established treatments such as allogenic bone graft. However, despite the surgical options available, correct healing can be slowed down or compromised by insufficient vascular supply to the injured site. MATERIALS AND METHODS: In this pilot study, critical size bone defects in rabbit radius were treated with allograft bone, in combination with vascular bundle and autologous bone marrow concentrate seeded onto a commercial collagen scaffold. Microtomographical, histological and immunohistochemical assessments were performed to evaluate allograft integration and bone regeneration. RESULTS: Results showed that the surgical deviation of vascular bundle in the bone graft, regardless from the addition of bone marrow concentrate, promote the onset of healing process at short experimental times (8 wk) in comparison with the other groups, enhancing graft integration. CONCLUSION: The surgical procedure tested stimulates bone healing at early times, preserving native bone architecture, and can be easily combined with biological adjuvant.

Bone union formation in the rat mandibular symphysis using hydroxyapatite with or without simvastatin: effects on healthy, diabetic, and osteoporotic rats.

OBJECTIVE: The objective is to compare new bone formation in critical defects in healthy, diabetic, and osteoporotic rats filled with hydroxyapatite (HA) alone and HA combined with simvastatin (SV). MATERIALS AND METHODS: A total of 48 adult female Sprague-Dawley rats were randomized into three groups (n = 16 per group): Group, 1 healthy; Group 2, diabetics; and Group 3, osteoporotics. Streptozotocin was used to induce type 1 diabetes in Group 2, while bilateral ovariectomy was used to induce osteoporosis in Group 3. The central portion of the rat mandibular symphysis was used as a physiological critical bone defect. In each group, eight defects were filled with HA alone and eight with HA combined with SV. The animals were sacrificed at 4 and 8 weeks, and the mandibles were processed for micro-computed tomography to analyze radiological union and bone mineral density (BMD); histological analysis of the bone union; and immunohistochemical analysis, which included immunoreactivity of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2). RESULTS: In all groups (healthy, diabetics, and osteoporotics), the defects filled with HA + SV presented greater radiological bone union, BMD, histological bone union, and more VEGF and BMP-2 positivity, in comparison with bone defects treated with HA alone. CONCLUSIONS: Combined application of HA and SV improves bone regeneration in mandibular critical bone defects compared with application of HA alone in healthy, diabetic, and osteoporotic rats. CLINICAL RELEVANCE: This study might help to patients with osteoporosis or uncontrolled diabetes type 1, but future studies should be done.

How Is Bone Regeneration Influenced by Polymer Membranes? Insight into the Histological and Radiological Point of View in the Literature.

The aim of this study was to analyze published works that investigate the in vivo bone regeneration capacity of polymeric membranes loaded with active substances and growth factors. This scoping review's purpose was to highlight the histological and radiological interpretation of the locally produced effects of the polymer membranes studied so far. For the selection of the articles, a search was made in the PubMed and ScienceDirect databases, according to the PRISMA algorithm, for research/clinical trial type studies. The search strategy was represented by the formula "((biodegradable scaffolds AND critical bone defect) OR (polymers AND mechanical properties) OR (3Dmaterials AND cytotoxicity) AND bone tissue regeneration)" for the PubMed database and "((biodegradable scaffolds AND polymers) OR (polymers AND critical bone defects) OR (biodegradable scaffolds AND mechanical properties) AND bone tissue regeneration)" for the ScienceDirect database. Ethical approval was not required. Eligibility criteria included eight clinical studies published between 2018 and 2023. Our analysis showed that polymer membranes that met most histopathological criteria also produced the most remarkable results observed radiologically. The top effective scaffolds were those containing active macromolecules released conditionally and staged. The PLGA and polycaprolactone scaffolds were found in this category; they granted a marked increase in bone density and improvement of osteoinduction. But, regardless of the membrane composition, all membranes implanted in created bone defects induced an inflammatory response in the first phase.

Novel artificial tricalcium phosphate and magnesium composite graft facilitates angiogenesis in bone healing.

BACKGROUND: Bone grafting is the standard treatment for critical bone defects, but autologous grafts have limitations like donor site morbidity and limited availability, while commercial artificial grafts may have poor integration with surrounding bone tissue, leading to delayed healing. Magnesium deficiency negatively impacts angiogenesis and bone repair. Therefore, incorporating magnesium into a synthetic biomaterial could provide an excellent bone substitute. This study aims to evaluate the morphological, mechanical, and biological properties of a calcium phosphate cement (CPC) sponge composed of tetracalcium phosphate (TTCP) and monocalcium phosphate monohydrate (MCPM), which could serve as an excellent bone substitute by incorporating magnesium. METHODS: This study aims to develop biomedical materials composed mainly of TTCP and MCPM powder, magnesium powder, and collagen. The materials were prepared using a wet-stirred mill and freeze-dryer methods. The particle size, composition, and microstructure of the materials were investigated. Finally, the biological properties of these materials, including 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay for biocompatibility, effects on bone cell differentiation by alkaline phosphatase (ALP) activity assay and tartrate-resistant acid phosphatase (TRAP) activity assay, and endothelial cell tube formation assay for angiogenesis, were evaluated as well. RESULTS: The data showed that the sub-micron CPC powder, composed of TTCP/MCPM in a 3.5:1 ratio, had a setting time shorter than 15 minutes and a compressive strength of 4.39±0.96 MPa. This reveals that the sub-micron CPC powder had an adequate setting time and mechanical strength. We found that the sub-micron CPC sponge containing magnesium had better biocompatibility, including increased proliferation and osteogenic induction effects without cytotoxicity. The CPC sponge containing magnesium also promoted angiogenesis. CONCLUSION: In summary, we introduced a novel CPC sponge, which had a similar property to human bone promoted the biological functions of bone cells, and could serve as a promising material used in bone regeneration for critical bone defects.

Critical Bone Defect Affecting the Outcome of Management in Anatomical Type IV Chronic Osteomyelitis.

Background: The Cierny and Mader classification assists with decision-making by stratifying host status and the pathoanatomy of the disease. However, the anatomical type IV represents a heterogenous group with regard to treatment requirements and outcomes. We propose that modification of the Cierny and Mader anatomical classification with an additional type V classifier (diffuse corticomedullary involvement with an associated critical bone defect) will allow more accurate stratification of patients and tailoring of treatment strategies. Methods: A retrospective review of 83 patients undergoing treatment for Cierny and Mader anatomical type IV osteomyelitis of the appendicular skeleton at a single centre was performed. Results: Risk factors for the presence of a critical bone defect were female patients [OR 3.1 (95% CI, 1.08-8.92)] and requirement for soft tissue reconstruction [OR 3.35 (95% CI, 1.35-8.31)]; osteomyelitis of the femur was negatively associated with the presence of a critical bone defect [OR 0.13 (95% CI, 0.03-0.66)]. There was no statistically significant risk of adverse outcomes (failure to eradicate infection or achieve bone union) associated with the presence of a critical-sized bone defect. The median time to the bone union was ten months (95% CI, 7.9-12.1 months). There was a statistically significant difference in the median time to bone union between cases with a critical bone defect [12.0 months (95% CI, 10.2-13.7 months)] and those without [6.0 months (95% CI, 4.8-7.1 months)]. Conclusion: This study provided evidence to support the introduction of a new subgroup of the Cierny and Mader anatomical classification (Type V). Using a standardised approach to management, comparable early outcomes can be achieved in patients with Cierny and Mader anatomical type V osteomyelitis. However, to achieve a successful outcome, there is a requirement for additional bone and soft tissue reconstruction procedures with an associated increase in treatment time. How to cite this article: Tsang STJ, Epstein GZ, Ferreira N. Critical Bone Defect Affecting the Outcome of Management in Anatomical Type IV Chronic Osteomyelitis. Strategies Trauma Limb Reconstr 2024;19(1):26-31.

Scaffold-Free Bone Marrow-Derived Mesenchymal Stem Cell Sheets Enhance Bone Formation in a Weight-Bearing Rat Critical Bone Defect Model.

Researchers have been exploring alternative methods for bone tissue engineering, as current management of critical bone defects may be a significant challenge for both patient and surgeon with conventional surgical treatments associated with several potential complications and drawbacks. Recent studies have shown mesenchymal stem cell sheets may enhance bone regeneration in different animal models. We investigated the efficacy of implanted scaffold-free bone marrow-derived mesenchymal stem cell (BMSC) sheets on bone regeneration of a critical bone defect in a weight-bearing rat model. BMSCs were isolated from the femora of male Sprague-Dawley rats 5-6 weeks of age and cell sheets were produced on temperature-responsive culture dishes. Nine male Sprague-Dawley rats 6-8 weeks of age were utilized. A bilateral femoral critical bone defect was created with a bridge plate serving as internal fixation. One side was randomly selected and BMSC sheets were implanted into the bone defect (BMSC group), with the contralateral side receiving no treatment (control). Rats were anesthetized and radiographs were performed at 2-week intervals. At the 8-week time point, rats were euthanized, femurs harvested, and microcomputed tomography and histological analysis was performed. We found a statistically significant increase in new bone formation and bone volume fraction compared with the control. Histomorphometry analysis revealed a larger percent of newly formed bone and a higher total histological score. Our results suggest that scaffold-free BMSC sheets may be used in the management of large weight-bearing bone defects to complement a different surgical technique or as a standalone approach followed by internal fixation. However, further research is still needed.

Evaluation of Biocomposite Cements for Bone Defect Repair in Rat Models.

Repairing or reconstructing significant bone defects is typically challenging. In the present study, two composite cements were used as scaffolds in a sub-critical femoral defect in rats. A control group and two experimental batches were used to compare the outcomes. This research aimed to investigate the osteogenic potential and toxicological tolerance of the bioproducts through histopathology and computed tomography imaging analysis at 14, 28, 56, and 90 days post-implantation. The biomaterials used in the investigation consisted of a 65% bioactive salinized inorganic filler and a 25% weight organic matrix. The organic part of the biomaterial was composed of Bis-GMA (bisphenol A-glycidyl methacrylate), UDMA (urethane dimethacrylate), HEMA (2-Hydroxyethyl methacrylate), and TEGDMA (triethylene glycol dimethacrylate), while the inorganic filler was composed of silica, barium glass, hydroxyapatite, and fluor aluminosilicate glass. The first findings of this research are encouraging, revealing that there is a slight difference between the groups treated with biomaterials, but it might be an effective approach for managing bone abnormalities. Material C1 exhibited a faster bone defect healing time compared to material C2, where bone fractures occurred in some individuals. It is unclear if the fractures were caused by the presence of the biomaterial C2 or whether additional variables were to blame. By the end of the research, the mice appeared to tolerate the biomaterials without exhibiting any inflammatory or rejection responses.

Local FK506 delivery induces osteogenesis in rat bone defect and rabbit spine fusion models.

Bone grafting procedures are commonly used for the repair, regeneration, and fusion of bones in a wide range of orthopaedic surgeries, including large bone defects and spine fusion procedures. Autografts are the clinical gold standard, though recombinant human bone morphogenetic proteins (rhBMPs) are often used, particularly in difficult clinical situations. However, treatment with rhBMPs can have off-target effects and increase surgical costs, adding to patients' already high economic and mental burden. Recent studies have identified that FDA-approved immunosuppressant drug, FK506 (Tacrolimus), can also activate the BMP pathway by binding to its inhibitors. This study tested the hypothesis that FK506, as a standalone treatment, could induce osteogenic differentiation of human mesenchymal stromal cells (hMSCs), as well as functional bone formation in a rat segmental bone defect model and rabbit spinal fusion model. FK506 enhanced osteogenic differentiation and mineralization of hMSCs in vitro. Standalone treatment with FK506 delivered on a collagen sponge produced consistent bone bridging of a critically sized rat femoral defect with functional mechanical properties comparable to naïve bone. In a rabbit single level posterolateral spine fusion model, treatment with FK506 delivered on a collagen sponge successfully fused the L5-L6 vertebrae at rates comparable to rhBMP-2 treatment. These data demonstrate the ability of FK506 to induce bone formation in human cells and two challenging in vivo models, and indicate FK506 can be utilized to treat a variety of spine disorders.

Application of the Modified RUST Score in Tibial Bone Transport and Factors Associated with Docking Site Complications.

Aim: Reconstruction of segmental bone defects with bone transport is a well-established treatment. Mechanical complications at the docking site after frame removal are common. These complications include malunion, non-union, axial deviation and refracture. A simple tool to assess the healing of the docking site is currently lacking. The aim of this study is to evaluate the use of the modified RUST (mRUST) score in the setting of bone transport and to identify factors associated with an increased risk of docking site complications. Methods: This retrospective study was conducted at a single tertiary centre in South Africa, included 24 patients with a tibial bone defect treated with bone transport and a circular frame between 2014 and 2023. Demographic data, clinical and bone transport characteristics were recorded. Mechanical complications, such as fracture, non-union, any angulation >5°, shortening >5 mm, or any other complication requiring reoperation, were recorded. The mRUST was adapted as a ratio for the purpose of this study to overcome the common occurrence of cortices being obscured by the frame. The mRUST ratio was applied before and after frame removal for each patient by three appraisers. Comparison between the groups with and without complications was performed regarding bone transport characteristics, docking site configuration and mRUST ratio. The correlation of the score between radiographs before and after frame removal was assessed. The inter-rater reliability of the mRUST was analysed using Fleiss Kappa statistics for each cortex individually and the intraclass correlation coefficient (ICC) for the mRUST ratio. Results: In this study, 20 men and 4 women with a median age of 26 years were included. The overall rate of mechanical complications after frame removal was 21.7%. Complications were all related to the docking site, with two angulations, two fractures and one non-union. Demographics, bone transport characteristics and mRUST ratio before and after frame removal were similar between the two groups. Regarding the configuration of the docking site, an angle of 45° or more between the bone surfaces was associated with the occurrence of mechanical complications (p < 0.001). The correlation of the mean mRUST ratio before and after frame removal showed a moderate relationship, with a Spearman correlation coefficient of 0.50 (p-value 0.13). The inter-rater reliability of the mRUST was "fair" (kappa 0.21-0.40) for the scoring of individual cortices, except for one score which was "slight" (kappa 0.00-0.20). The ICC of the mRUST ratio was 0.662 on radiographs with the frame, and 0.759 after frame removal. Conclusion: This study did not find the mRUST or mRUST ratio useful in assessing the healing of the docking site to decide on the best time to remove the frame. However, a notable finding was that the shape and orientation of the bone ends meeting at the docking site might well be relevant to decrease complication rates. If the angle between the bony surfaces is 45° or more, it may be associated with an increased risk of complications. It may be worthwhile considering reshaping these bone ends at the time of debridement or formal docking procedure to be more collinear, in order to reduce the potential for mechanical complications such as non-union, axial deviation or refracture at the docking site. How to cite this article: Kummer A, Nieuwoudt L, Marais LC. Application of the Modified RUST Score in Tibial Bone Transport and Factors Associated with Docking Site Complications. Strategies Trauma Limb Reconstr 2024;19(2):73-81.

Bioglass/collagen scaffolds combined with bone marrow stromal cells on bone healing in an experimental model in cranial defects in rats.

This study aimed to develop bone regenerative therapeutic strategies, based on the addition of bone marrow stromal cells (BMSC) on bioglass/collagen (BG/COL) scaffolds. For this purpose, an in vivo study was conducted using tissue response of the BG/COL scaffolds combined with BMSC in a critical-size defects. Wistar rats were submitted to the surgical procedure to perform the cranial critical size bone defects and distributed in four groups (20 animals per group): Control Group (CG) (rats submitted to the cranial bone defect surgery without treatment), Bioglass Group (BG) (rats treated with BG), BG/COL Group (rats treated with BG/COL) and Bioglass/Collagen and BMSC Group (BG/COL/BMSC) (rats treated with BG/COL scaffolds enriched with BMSCs). Animals were euthanized 15 and 30 days after surgery. Scanning electron microscopy, histopathological and immunohistochemistry analysis were used. SEM analysis demonstrated that porous scaffolds were obtained, and Col fibers were successfully impregnated to BG matrices. The implantation of the BMSC on BG/COL based scaffolds was effective in stimulating newly bone formation and produced an increased immunoexpression of markers related to the bone repair. These results highlight the potential of BG/COL scaffolds and BMSCs to be used as a therapeutic approach for bone regeneration.

Engineering 3D-Printed Strontium-Titanium Scaffold-Integrated Highly Bioactive Serum Exosomes for Critical Bone Defects by Osteogenesis and Angiogenesis.

Currently, healing of large bone defects faces significant challenges such as a bulk of bone regeneration and revascularization on the bone defect region. Here, a "cell-free scaffold engineering" strategy that integrates strontium (Sr) and highly bioactive serum exosomes (sEXOs) inside a three-dimensional (3D)-printed titanium (Ti) scaffold (Sc) is first developed. The constructed SrTi Sc can serve as a sophisticated biomaterial platform for maintaining bone morphological characteristics of the radius during the period of critical bone defect (CBD) repair and further accelerating bone formation and fibroblastic suppression via the controlled release of Sr from the superficial layer of the scaffold. Moreover, compared with sEXO from healthy donors, the sEXO extracted from the serum of the femoral fracture rabbit model at the stage of fracture healing, named BF EXO, is robustly capable of facilitating osteogenesis and angiogenesis. In addition, the underlying therapeutic mechanism is elucidated, whereby altering miRNAs shuttled by BF EXO enables osteogenesis and angiogenesis. Further, the in vivo study revealed that the SrTi Sc + BF EXO composite dramatically accelerated bone repair via osteoconduction, osteoinduction, and revascularization in radial CBD of rabbits. This study broadens the source and biomedical potential of specifically functionalized exosomes and provides a comprehensive clinically feasible strategy for therapeutics on large bone defects.

One Stage Masquelets Technique: Evaluation of Different Forms of Membrane Filling with and without Bone Marrow Mononuclear Cells (BMC) in Large Femoral Bone Defects in Rats.

The classic two-stage masquelet technique is an effective procedure for the treatment of large bone defects. Our group recently showed that one surgery could be saved by using a decellularized dermis membrane (DCD, Epiflex, DIZG). In addition, studies with bone substitute materials for defect filling show that it also appears possible to dispense with the removal of syngeneic cancellous bone (SCB), which is fraught with complications. The focus of this work was to clarify whether the SCB can be replaced by the granular demineralized bone matrix (g-DBM) or fibrous demineralized bone matrix (f-DBM) demineralized bone matrix and whether the colonization of the DCD and/or the DBM defect filling with bone marrow mononuclear cells (BMC) can lead to improved bone healing. In 100 Sprague Dawley rats, a critical femoral bone defect 5 mm in length was stabilized with a plate and then encased in DCD. Subsequently, the defect was filled with SCB (control), g-DBM, or f-DBM, with or without BMC. After 8 weeks, the femurs were harvested and subjected to histological, radiological, and biomechanical analysis. The analyses showed the incipient bony bridging of the defect zone in both groups for g-DBM and f-DBM. Stability and bone formation were not affected compared to the control group. The addition of BMCs showed no further improvement in bone healing. In conclusion, DBM offers a new perspective on defect filling; however, the addition of BMC did not lead to better results.

Tibialization of fibula in critical bone defect due to post traumatic osteomyelitis of the tibial shaft: A case report.

INTRODUCTION AND IMPORTANCE: Post-traumatic osteomyelitis in patients with an open fracture is one of the most common causes of a bone defect after an extensive debridement and one of the most challenging complications to treat. Removal of devitalized and infected tissue may result in a large defect that requires subsequent reconstruction. CASE PRESENTATION: Two patients that underwent tibialization were included in this study. The first patient is a 32-year-old male with an infected non-union of the left shaft tibia and the second patient is a 10-year-old boy with a gap non-union of the right shaft tibia due to open fracture with bone loss. Both patients resulted in proximal and distal bone union and full weight bearing on the affected leg without limitation and pain. Nine months Follow up for the first patient show the proximal and distal bone union and an addition to the width of the fibular graft in X-ray examination showing promising results. For the second patient, follow-up 12 months after surgery shows a complete union of the proximal and distal bone union. CLINICAL DISCUSSION: Debridement would lead to soft tissue loss, which usually results in large injury defects. Tibialization of the fibula, also known as fibula pro tibia grafting, is one of the known reconstruction methods in treating patients with segmental defects in the tibia. CONCLUSION: Critical bone defects remain one of the most challenging orthopaedic conditions to treat. Tibialization is an excellent option with an acceptable functional outcome to treat critical bone defects.

Carboxymethyl chitosan-alginate enhances bone repair effects of magnesium phosphate bone cement by activating the FAK-Wnt pathway.

There is a continuing need for artificial bone substitutes for bone repair and reconstruction, Magnesium phosphate bone cement (MPC) has exceptional degradable properties and exhibits promising biocompatibility. However, its mechanical strength needs improved and its low osteo-inductive potential limits its therapeutic application in bone regeneration. We functionally modified MPC by using a polymeric carboxymethyl chitosan-sodium alginate (CMCS/SA) gel network. This had the advantages of: improved compressive strength, ease of handling, and an optimized interface for bioactive bone in-growth. The new composites with 2% CMCS/SA showed the most favorable physicochemical properties, including mechanical strength, wash-out resistance, setting time, injectable time and heat release. Biologically, the composite promoted the attachment and proliferation of osteoblast cells. It was also found to induce osteogenic differentiation in vitro, as verified by expression of osteogenic markers. In terms of molecular mechanisms, data showed that new bone cement activated the Wnt pathway through inhibition of the phosphorylation of ß-catenin, which is dependent on focal adhesion kinase. Through micro-computed tomography and histological analysis, we found that the MPC-CMCS/SA scaffolds, compared with MPC alone, showed increased bone regeneration in a rat calvarial defect model. Overall, our study suggested that the novel composite had potential to help repair critical bone defects in clinical practice.

Zoledronate loaded polylactic acid/polycaprolactone/hydroxyapatite scaffold accelerates regeneration and led to enhance structural performance and functional ability of the radial bone defect in rat.

Abstract. Background: One of the most common concerns in the regeneration of massive bone defects necessitating surgery and bone grafts is the application of tissue engineering using drug delivery. Zoledronate is a well-known effective drug for the healing bone fractures in osteoporotic patients. Aims: An attempt was made to design a more efficient bone scaffold with polycaprolactone, polylactic acid, and hydroxyapatite. Methods: The scaffold was fabricated by freeze-drying and indirect 3D printing approaches. X-ray diffraction, Fourier transform infrared spectroscopy, rheometry, scanning electron microscopy, and neutral red tests were performed to characterize the scaffold. qRT-PCR was also done to define the osteoinductivity and angiogenic induction capacity of this scaffold. Forty rats were selected and randomly divided into four groups: the control group, which received no treatment, the autograft group, scaffold group, and Zol-loaded scaffold group (n=10 in each group). The injured area was studied by radiology, biomechanical analysis, histopathology, histomorphometry, immunohistochemistry, and CT scan analyses. Results: The qRT-PCR results demonstrated significantly higher expression levels of OPN, OCN, and CD31 markers in the scaffold group when compared to the control group (P<0.05). Histopathologically, the newly formed bone tissue was significantly detected in the Zol-loaded scaffold and autograft groups in comparison with the non-treated group (P<0.001). The immunohistochemistry (OC marker), biomechanical, and histomorphometric results indicated a significant improvement in the regeneration of the injured area in the groups treated with autologous bone and Zol-loaded scaffold compared to the non-treated group (P<0.05). Conclusion: The Zol-loaded scaffold accelerated bone regeneration, and led to enhanced structural performance and functional ability of the injured radial bone in rats.

Strategies of immobilizing BMP-2 with 3D-printed scaffolds to improve osteogenesis.

The management and definitive treatment of critical-size bone defects in severe trauma, tumor resection and congenital malformation are troublesome for orthopedic surgeons and patients worldwide without recognized good treatment strategies. Researchers and clinicians are working to develop new strategies to treat these problems. This review aims to summarize the techniques used by additive manufacturing scaffolds loaded with BMP-2 to promote osteogenesis and to analyze the current status and trends in relevant clinical translation. Optimize composite scaffold design to enhance bone regeneration through printing technology, material selection, structure design and loading methods of BMP-2 to advance the clinical therapeutic bone repair field.

Some people have considerable bone gaps because of accidents, cancer or congenital disabilities. These gaps are difficult to heal and can cause many problems. Doctors and scientists are trying to find new ways to help these people. One way is to make artificial pieces of bone that can fit into the gaps and help the bone grow back. These are made using special machines that can print different shapes and materials. They also contain a protein called BMP-2, which allows the bones to grow faster. This article examines how these parts are made and how they can be used in patients. It also suggests how they might be improved in the future.

The Pedicled Fibula Flap for Lower Limb Reconstruction.

The pedicled fibula flap is a reliable technique to treat large defects in the tibia. Despite increasing evidence of its efficacy and good long-term outcomes, a knowledge gap exists in its indications and technique. This instructional article presents a comprehensive overview of the indications, pre-operative planning, step-by-step surgery, and subsequent post-operative management. How to cite this article: Noorlander-Borgdorff MP, Giannakópoulos GF, Winters HAH, et al. The Pedicled Fibula Flap for Lower Limb Reconstruction. Strategies Trauma Limb Reconstr 2023;18(3):186-193.

Engineering Multifunctional Hydrogel With Osteogenic Capacity for Critical-Size Segmental Bone Defect Repair.

Treating critical-size segmental bone defects is an arduous challenge in clinical work. Preparation of bone graft substitutes with notable osteoinductive properties is a feasible strategy for critical-size bone defects. Herein, a biocompatible hydrogel was designed by dynamic supramolecular assembly of polyvinyl alcohol (PVA), sodium tetraborate (Na2B4O7), and tetraethyl orthosilicate (TEOS). The characteristics of the supramolecular hydrogel were evaluated by rheological analysis, swelling ratio, degradation experiments, and scanning electron microscopy (SEM). In in vitro experiments, this TEOS-hydrogel had self-healing property, low swelling rate, degradability, good biocompatibility, and induced osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by upregulating the expression of Runx-2, Col-1, OCN, and osteopontin (OPN). In segmental bone defect rabbit models, the TEOS-containing hydrogel accelerated bone regeneration, thus restoring the continuity of bone and recanalization of the medullary cavity. The abovementioned results demonstrated that this TEOS-hydrogel has the potential to realize bone healing in critical-size segmental bone defects.

Dexamethasone-Loaded Ureasil Hydrophobic Membrane for Bone Guided Regeneration.

Physical barrier membranes have been used to release active substances to treat critical bone defects; however, hydrophilic membranes do not present a prolonged release capacity. In this sense, hydrophobic membranes have been tested. Thus, this study aimed to develop hydrophobic membranes based on mixtures of ureasil-polyether-type materials containing incorporated dexamethasone (DMA) for the application in guided bone regeneration. The physicochemical characterization and biological assays were carried out using small-angle X-ray scattering (SAXS), an in vitro DMA release study, atomic force microscopy (AFM), a hemolysis test, and in vivo bone formation. The swelling degree, SAXS, and release results revealed that the u-PPO400/2000 membrane in the proportion of 70:30 showed swelling (4.69% ± 0.22) similar to the proportions 90:10 and 80:20, and lower than the proportion 60:40 (6.38% ± 0.49); however, an equal release percentage after 134 h was observed between the proportions 70:30 and 60:40. All u-PPO materials presented hemocompatibility (hemolysis ≤2.8%). AFM results showed that the treatments with or without DMA did not present significant differences, revealing a flat/smooth surface, with no pores and/or crystalline precipitates. Finally, in vivo results revealed that for both the commercial hydrophilic membrane and u-PPO400/2000 (70:30) after 60 days, the bone formation volume was 21%. In conclusion, hybrid membranes present unique characteristics for treating critical bone defects, considering the delayed and prolonged release results associated with the physical barrier capacity.