Promote Bone Healing Research Articles

Application of Light-Responsive Nanomaterials in Bone Tissue Engineering

The application of light-responsive nanomaterials (LRNs) in bone tissue engineering shows broad prospects, especially in promoting bone healing and regeneration. With a deeper understanding of the mechanisms of bone defects and healing disorders, LRNs are receiving increasing attention due to their non-invasive, controllable, and efficient properties. These materials can regulate cellular biological reactions and promote bone cell adhesion, proliferation, and differentiation by absorbing specific wavelengths of light and converting them into physical and chemical signals. In addition, the unique surface morphology and biocompatibility of LRNs enable them to effectively load drugs in bone tissue engineering, achieve precise release, and optimize the bone regeneration process. Through photothermal and photodynamic therapy, these materials also possess antibacterial properties and can play an important role in the repair of infectious bone defects. Although LRNs have shown significant advantages in bone tissue regeneration, a series of challenges still need to be overcome to achieve their widespread and effective clinical applications. This article summarizes the basic principles, classification, and potential applications of LRNs in bone tissue regeneration, aiming to provide reference for future research and clinical applications.

Curcumin-carbon dots suppress periodontitis via regulating METTL3/IRE1α signaling.

This study aimed to investigate the effects of curcumin-carbon dot conjugates (CUR-CD) on periodontitis. Porphyromonas gingivalis lipopolysaccharide (LPS) was used to establish periodontitis mode in vivo and in vitro. Histological analysis was conducted using hematoxylin and eosin (HE) staining. Bone morphogenetic protein 2 (BMP2) and secreted phosphoprotein 1 (OPN) expression was determined using immunohistochemistry. mRNA levels were detected using reverse transcription quantitative real-time PCR (RT-qPCR). Protein expression was determined using Western blot. N6-methyladenosine (m6A) enrichment was determined using methylated RNA immunoprecipitation (MeRIP) assay. Cytokine release was determined using enzyme-linked immunosorbent assay (ELISA) assay. Osteogenic differentiation was detected using alkaline phosphatase (ALP) staining. The results showed that CUR-CD inhibited the inflammatory response, as well as promoted bone healing in vivo and osteogenic differentiation in vitro. Moreover, CUR-CD downregulated methyltransferase 3 (METTL3), which inhibited m6A modification of endoplasmic reticulum to nucleus signaling 1 (IRElα) and downregulated IRElα expression. However, overexpression of IRElα reversed the effects of CUR-CD, stimulating inflammatory response and inhibiting bone healing and osteogenic differentiation. Collectively, CUR-CD inhibits the progression of periodontitis via downregulating IRElα. Therefore, CUR-CD may be an alternative strategy for periodontitis.

Treatment of lumbar spondylolysis in young adults using modified intravertebral screw-rod fixation system for single vertebral body combined with autologous cancellous bone graft: a technical note and preliminary report

BackgroundThere is currently no consensus on the surgical treatment of lumbar spondylolysis in young adults, and the nonunion rate remains relatively high even after surgery. Therefore, in this study, we proposed a modified intravertebral screw-rod fixation technique within a single vertebral segment and investigated the clinical efficacy of this modified fixation system combined with autologous cancellous bone grafting in the treatment of lumbar spondylolysis in young adults.MethodsThis study included 28 young adults with lumbar spondylolysis who were treated at our center between 2021 and 2023. All patients underwent modified intravertebral screw-rod fixation within a single vertebral segment combined with autologous cancellous bone grafting. We performed postoperative follow-ups regularly to assess the patient’s pain status using the visual analog scale (VAS), Oswestry Disability Index (ODI), and radiological findings.ResultsAll 28 patients successfully underwent the surgery with an average operation time and blood loss volume of 96.01 ± 21.3 min and 186.78 ± 63.43 mL, respectively. Postoperatively, patients experienced significant symptom relief, with notable decreases in VAS scores and ODI indices at 1, 3, 6, and 12 months compared with preoperative conditions. These differences were statistically significant (P < 0.05). Radiological findings revealed a healing rate of 92.86% for the 56 fractured pars interarticularis among the 28 patients. No implant-related complications, such as fracture, loosening, or pseudarthrosis, were observed.ConclusionsThe modified intravertebral screw-rod fixation system within a single vertebral segment combined with autologous cancellous bone grafting is a safe and effective treatment for lumbar spondylolysis in young adults. It significantly improves pain and functional disability as it promotes bone healing.

Positive Results Using Variable Fixation in Medial Opening Wedge High Tibial Osteotomies in Patients with Unilateral Knee Osteoarthritis: An Observational Clinical Investigation.

Background: Medial opening wedge high tibial osteotomy (HTO) treats medial knee osteoarthritis by realigning the knee joint, though it still carries quite a high risk of complications. A new Variable Fixation Locking Screw technology, designed to gradually reduce construct stiffness and promote bone healing, aims to address these issues. This observational study evaluates the safety and effectiveness of this innovative approach in improving clinical outcomes. Methods: Data were prospectively collected on a cohort of the first ten consecutive patients (over 18 years of age) who underwent corrective medial opening wedge high tibial osteotomy using Variable Fixation Locking Screws (VFLSs). The procedure followed the standard surgical technique, with osteotomies stabilized using a Tomofix plate and a combination of standard locking screws and VFLSs. This study aimed to evaluate outcomes such as fracture healing, patient safety, and procedural success at 6 and 12 weeks and at 6 months. Results: No complications, side effects, or need for implant removal were observed. By six months, 70% of patients showed radiographic and clinical healing, and 100% of patients achieved full functional recovery without any issues like length discrepancy, instability, pain, or joint stiffness. Conclusions: This first clinical observation study indicates that Variable Fixation Locking Screws are safe and effective for medial opening wedge high tibial osteotomies, showing promising results in reducing the risk of delayed closure or non-closure of the wedge. Further studies with a larger patient population are needed to confirm their effectiveness.

Denosumab combined with radiotherapy as an alternative to surgery for advanced metastatic bone lesions and pathologic fractures: a retrospective case study of 38 patients.

Pathologic and impending fractures occur in patients with advanced metastatic disease and necessitate surgical interventions with high risk of complications. The aim of this study was to analyze the efficacy of combined treatment with denosumab and radiotherapy as an alternative to surgery in treating bone metastases of the pelvis and extremities. This retrospective cohort study included 38 patients with impending and pathologic fractures due to carcinoma metastases who received monthly injections of denosumab (120 mg/dose) and radiotherapy. Twenty-three patients received denosumab and single-dose radiotherapy of 8 Gy, and 15 patients received denosumab and fractionated radiotherapy. We assessed pain, radiographic signs of fracture healing, survival and complications. Of the 38 patients 36 experienced pain reduction. Callus formation was observed in 11/17 patients with pathologic fractures, and increased mineralization was found in 12/21 patients with impending fractures. In 23/38 patients, we found both pain reduction and callus formation or increased mineralization. There were no statistically significant differences in treatment outcomes between the patients who received denosumab and single-dose radiotherapy and those who received denosumab and fractionated radiotherapy. The survival rates at 30 days and 1 year were 95% and 56%, respectively. Combined treatment with denosumab and radiotherapy may reduce pain and promote bone healing in patients with metastatic impending and pathologic fractures. In this combined treatment, the effect of single-dose radiotherapy appears to be comparable to that of fractionated regimens.

Exogenous bone sialoprotein improves extraction socket healing in ibsp knockout and wild-type mice.

Bone sialoprotein (Ibsp/BSP) is a bone-associated extracellular matrix protein. Ibsp knockout (Ibsp-/-) mice exhibit defective alveolar bone formation, mineralization, and healing. We hypothesized BSP would rescue defective alveolar bone healing in a molar extraction model in Ibsp-/- mice. Collagen gel with or without native rat BSP (nBSP) or recombinant rat BSP (rBSP) was delivered to sockets after first maxillary molar extraction in Ibsp-/- and wild-type (WT) mice. Tissues were harvested 0, 1, 2, 7, and 14 days post-procedure (dpp) and analyzed by micro-computed tomography, histology, and immunohistochemistry (IHC). Histology and IHC demonstrated that collagen and BSP were retained within sockets. At 14 dpp, both bone volume fraction (BV/TV) and bone mineral density (BMD) were increased by both nBSP (over 50 %) and rBSP (over 60 %), compared to collagen alone in Ibsp-/- mice. In WT alveolar bone, BV/TV and BMD were also increased by nBSP (over 30 %) and rBSP (over 60 %) compared to collagen controls. Gene expression analyses revealed few changes from delivery of nBSP, while addition of rBSP resulted in regulation of cell signaling, ECM, mineralization, and osteoblast/osteoclast-associated genes. Exogenous BSP rescued alveolar bone healing defects in Ibsp-/- mice and enhanced bone healing in WT mice. Despite both forms of BSP improving bone healing, the substantial differences in how they regulate gene expression suggests that exogenous BSP acts in a complex, multifunctional manner to promote bone healing. These results support BSP as a novel approach to improve the quantity and quality of new bone in socket healing.

Synergistic Effects of Platelet-rich Fibrin and Photobiomodulation on Bone Regeneration in MC3T3-E1 Preosteoblasts

Platelet-rich fibrin (PRF) and Photobiomodulation (PBM) are established methods for promoting bone healing. PRF enhances cell proliferation and migration due to its rich concentration of growth factors, while PBM stimulates tissue repair through mitochondrial activation. Despite their efficacies, no in-depth studies have explored the synergistic effects of combining PRF and PBM. PRF was prepared at 50% and 100% concentrations, and PBM was applied using an 830 nm near-infrared laser at a dose of 5 J/cm². Cell viability, migration, and calcium deposition were assessed over seven and fourteen days. The combination of PRF and PBM significantly improved cell viability, migration, and calcium deposition, with the most notable effects observed after seven and fourteen days. However, a slight decrease in calcium deposition was noted in the 100% PRF combined with the PBM group, suggesting a potential feedback mechanism at higher PRF concentrations. This study is the first to explore the synergistic effects of PRF and PBM, offering new insights into optimizing bone tissue engineering strategies. The findings highlight the potential of this combined approach in enhancing bone regeneration, although further research is needed to refine the optimal conditions for these therapies.

Selective Pyk2 inhibition enhances bone restoration through SCARA5-mediated bone marrow remodeling in ovariectomized mice

Understanding the intricate cellular interactions involved in bone restoration is crucial for developing effective strategies to promote bone healing and mitigate conditions such as osteoporosis and fractures. Here, we provide compelling evidence supporting the anabolic effects of a pharmacological Pyk2 inhibitor (Pyk2-Inh) in promoting bone restoration. In vitro, Pyk2 signaling inhibition markedly enhances alkaline phosphatase (ALP) activity, a hallmark of osteoblast differentiation, through activation of canonical Wnt/β-catenin signaling. Notably, analysis of human mesenchymal stem cells through RNA-seq revealed a novel candidate, SCARA5, identified through Pyk2-Inh treatment. We demonstrate that Scara5 plays a crucial role in suppressing the differentiation from stromal cells into adipocytes, and accelerates lineage commitment to osteoblasts, establishing Scara5 as a negative regulator of bone formation. Additionally, Pyk2 inhibition significantly impedes osteoclast differentiation and bone resorption. In a co-culture system comprising osteoblasts and osteoclasts, Pyk2-Inh effectively suppressed osteoclast differentiation, accompanied by a substantial increase in the transcriptional expression of Tnfrsf11b and Csf1 in osteoblasts, highlighting a dual regulatory role in osteoblast-osteoclast crosstalk. In an ovariectomized mouse model of osteoporosis, oral administration of Pyk2-Inh significantly increased bone mass by simultaneously reducing bone resorption, promoting bone formation and decreasing bone marrow fat. These results suggest Pyk2 as a potential therapeutic target for both adipogenesis and osteogenesis in bone marrow. Our findings underscore the importance of Pyk2 signaling inhibition as a key regulator of bone remodeling, offering promising prospects for the development of novel osteoporosis therapies.

Bee Propolis: Nature’s Remedy for Bone Healing – A Narrative Review

Propolis is a resin-like compound bees produce from botanical substances mixed with their saliva and beeswax. It contains antioxidants like flavonoids and phenolic acids that promote bone healing. The promising potential of propolis in supporting bone healing has significant implications in various medical and dental fields, such as orthopedics, periodontology, orthodontics, and oral and maxillofacial surgery. This review aims to evaluate the existing body of research on the impact of propolis on bone healing. A comprehensive literature search spanning the last two decades until 2024 was conducted across reputable databases utilizing the search terms “propolis AND bone AND alveolar bone AND healing. Articles with these keywords, published in English and accessible from reputable databases like PubMed, Cochrane Library, Scopus, and Google Scholar, were included. Articles from unreliable sources, non-English publications, those without full-text access, and review articles or letters to editors were excluded. Initially, 1,974 articles were identified, and after removing duplicates and applying the inclusion and exclusion criteria, 54 articles were selected, and 31 were deemed relevant for the review. The literature indicates that propolis offers significant advantages in halting the progression of bone loss and expediting bone formation and maturation, primarily due to its antioxidant and anti-inflammatory properties. Consequently, incorporating propolis could be an effective and cost-efficient strategy for managing bone defects.

TiNbSn alloy plates with low Young's modulus modulates interfragmentary movement and promote osteosynthesis in rat femur

Orthopedic implants such as arthroplasty prostheses, fracture plates, and intramedullary nails often use materials like Ti6Al4V alloy and commercially pure titanium (CP-Ti), which have Young's modulus significantly higher than that of human cortical bone, potentially causing stress shielding and inhibiting effective fracture healing. TiNbSn alloy, a β-type titanium alloy with a lower Young's modulus (40–49 GPa), has shown promise in reducing stress shielding and enhancing bone healing by promoting effective load sharing with bone. This study used 5-hole plates made from TiNbSn alloy and CP-Ti to investigate their effects on bone healing in a rat femoral fracture model. Micro-CT analysis and mechanical testing were performed six weeks postoperatively to assess bone healing. Additionally, Finite element method (FEM) analysis was employed to evaluate stress shielding and interfragmentary movement (IFM) at the fracture site. Micro-CT analysis revealed significantly higher bone volume and mineral density in the TiNbSn group than in the CP-Ti group. Mechanical testing showed increased maximum load and stiffness in the TiNbSn group (77.2 ± 10.0 N for the TiNbSn alloy plate group versus 53.3 ± 8.5 N for the CP-Ti group (p = 0.002)). FEM analysis indicated that TiNbSn plates reduced stress shielding and allowed for greater displacement and strain, promoting IFM conducive to bone healing. The findings suggest that TiNbSn alloy plates are more effective than CP-Ti plates in promoting bone healing by reducing stress shielding and enhancing IFM. The lower Young's modulus of TiNbSn allows better load distribution, facilitating bone regeneration and strengthening at the fracture site.

Novel Collagenous Sponge Composites for Osteochondral Regeneration in Rat Knee Models: A Comparative Study of Keratin, Hydroxyapatite, and Combined Treatments.

Thisstudy aims to evaluate the osteoconductive and osteoinductive potential of novel composite collagenous sponges enriched with keratin (K), hydroxyapatite (HA), and their combination (K+HA) for osteochondral regeneration in rat knee models. By examining cell proliferation, mineralization, and vascularization, we aim to determine the regenerative effectiveness of these materials in promoting osteochondral repair, particularly in load-bearing joints like the knee. Addressing the problem of osteochondral defects (OCD), which lead to osteoarthritis-a condition characterized by pain and functional impairment-the hereby research evaluates these biomaterials for their potential to foster bone and cartilage repair, especially in load-bearing joints as the knee. By leveraging an experimental living rat knee model, the effectiveness of these bio-composites is tasted through detailed morphological, biomechanical, and histological analyses. We have employed a rigorous methodology encompassing the selection of biomaterials based on their osteoconductive and osteoinductive traits, their intraosseous application in Wistar rats, and ulterior comprehensive and minutely monitoring. The comparison covers aspects such as cell growth, mean pixel intensity, and other key morphological properties, offering good insights into each material's regenerative capacity. Furthermore, in the present study we have highlighted the fabrication processes of the sponges, including lyophilization and crosslinking, underlining the importance of the biomaterials' physical characteristics in achieving targeted and optimal regenerative outcomes. Preliminary results obtained illustrate the biocompatibility and potential efficacy of these collagen-based composites in promoting bone healing and regeneration, with particular attention being given to the synergistic effects observed in the K+HA combination. This research will contribute to the understanding of material-based regeneration of osteochondral units but also might open avenues for future investigations into the optimization of such therapies for further clinical application. Through a detailed examination of the materials' integration with the test animal bone and cartilaginous tissues and their impact on bone and cartilage healing, this study sets the stage for the advancement of regenerative medicine solutions for OCD and the array of related conditions, offering hope for patients suffering from joint degeneration and injury.

COMPARISON OF AUTOGENOUS-BONE-GRAFT VS BONE-SUBSTITUTE IN NONUNION OF LONG BONES IN TERMS OF EARLY UNION

Background: Nonunion of long bones remains a challenge in orthopedic surgery, often resulting in pain, disability, and impaired function. While autogenous bone grafts (ABG) are traditionally preferred for their osteogenic properties, their use is limited by donor site morbidity. Bone substitutes like hydroxyapatite (HA) have emerged as alternatives due to their osteoconductive capabilities. Comparative studies are necessary to evaluate the effectiveness of ABG versus HA in achieving early union in nonunion cases. Objective: To compare the effectiveness of autogenous bone grafts and hydroxyapatite bone substitute in promoting early union in long bone nonunion. Methods: A randomized controlled trial was conducted at General Hospital, Lahore, Pakistan, from January 2021 to January 2023. Eighty patients with nonunion of long bones, aged 15 to 70 years, were enrolled via probability randomized sampling. Patients were randomly assigned to two groups: Group A received autogenous bone grafts, while Group B was treated with hydroxyapatite bone substitute. Clinical and radiological evaluations were conducted at regular intervals to assess bone union. Statistical analyses were performed using an independent t-test, with significance set at p &lt; 0.05. Results: The mean age of patients in Group A was 27.32 ± 12.17 years, while in Group B it was 31.10 ± 10.12 years. Group A comprised 37 males (92.5%) and 3 females (7.5%), whereas Group B included 34 males (85%) and 6 females (15%). Union rates were 90% in Group A and 85% in Group B, with no statistically significant difference (p = 0.499). Conclusion: This study indicates that both autogenous bone grafts and hydroxyapatite bone substitutes are effective in treating long bone nonunion, with slightly higher union rates observed in the ABG group. Both modalities provide viable options for promoting bone healing in nonunion cases.

Local Delivery of Exosomes and Antibiotics in Hydroxyapatite-Based Nanocement for Osteomyelitis Management.

The management of bone and joint infections is a formidable challenge in orthopedics and poses a global health concern. While clinical management emphasizes infection prevention and complete eradication, an effective strategy for stabilizing skeletal tissue with adequate soft tissue coverage remains limited. In this study, we have employed a novel approach of using the local delivery of exosomes and antibiotics (rifampicin) using a hydroxyapatite-based nanocement carrier to manage the residual space created during debridement effectively. Additionally, we synthesized a periosteum-guiding antioxidant herbal membrane to leverage the inherent periosteum regeneration capability of the bone, facilitating bone callus repair and natural healing. The synthesized scaffolds were biocompatible and demonstrated potent antibacterial activity in vitro. When evaluated in vivo in the Staphylococcus aureus-induced rat tibial osteomyelitis model, the released drugs successfully cleared the residual bacteria and the released exosome promoted bone healing, resulting in 3-fold increase in bone volume as analyzed via micro-CT analysis. Immunofluorescence staining of periosteum-specific markers also indicated the complete formation of periosteal layers, thus highlighting the complete bone repair.

Enhanced Experimental Setup and Methodology for the Investigation of Corrosion Fatigue in Metallic Biodegradable Implant Materials.

Biodegradable implants as bone fixations may present a safe alternative to traditional permanent implants, reducing the risk of infections, promoting bone healing, and eliminating the need for removal surgeries. Structural integrity is an important consideration when choosing an implant material. As a biodegradable implant is being resorbed, until the natural bone has regrown, the implant material needs to provide mechanical stability. However, the corrosive environment of the human body may affect the fatigue life of the material. Conversely, mechanical stress can have an effect on electrochemical corrosion processes. This is known as corrosion fatigue. In the presented work, an experimental setup and methodology was established to analyze the corrosion fatigue of experimental bioresorbable materials while simultaneously monitoring the electrochemical processes. A double-walled measurement cell was constructed for a three-point bending test in Dulbecco's Phosphate-Buffered Saline (DPBS- -), which was used as simulated body fluid (SBF), at 37 ± 1 °C. The setup was combined with a three-electrode setup for corrosion measurements. Rod-shaped zinc samples were used to validate the setup's functionality. Preliminary static and dynamic bending tests were carried out as per the outlined methodology to determine the test parameters. Open-circuit as well as potentiostatic polarization measurements were performed with and without mechanical loading. For the control, fatigue tests were performed in an air environment. The tested zinc samples were inspected via scanning electron microscopy (SEM). Based on the measured mechanical and electrochemical values as well as the SEM images, the effects of the different environments were investigated, and the setup's functionality was verified. An analysis of the data showed that a comprehensive investigation of corrosion fatigue characteristics is feasible with the outlined approach. Therefore, this novel methodology shows great potential for furthering our understanding of the effects of corrosion on the fatigue of biodegradable implant materials.

Association of fracture gap with implant failure in radius and ulna fractures in toy breed dogs-A multicenter retrospective cohort study.

To assess the impact of a postoperative fracture gap on implant failure following radius and ulna fracture repair in toy breed dogs. Retrospective multicenter cohort study. A total of 80 client-owned toy breed dogs. Medical records and radiographs were reviewed for dogs <3.5 kg that had surgical repair of simple transverse radius and ulna fractures at four institutions from 2005 to 2019. Data collected included signalment, fracture location, implant types and thickness, plate working length, evidence of a postoperative fracture gap in the caudal cortex, postoperative care, occurrence of implant failure, and other complications. The association between potential risk factors and complications was examined using multivariable logistic regression. A postoperative fracture gap in the caudal cortex was noted in 37 cases, and 10 cases experienced implant failure. Of the 43 cases without a gap, one case experienced implant failure. After adjusting for other variables, the fracture gap was significantly associated with implant failure (odds ratio = 23.0 [95% confidence interval: 2.7; 197.9], p = .004). Prolonged external coaptation was associated with minor and major complications other than implant failure (p = .04), while the absence of coaptation confounded the effects of the fracture gap on implant failure. Reduction of the caudal cortex of the radius is imperative to promote bone healing and prevent implant failure in transverse radius and ulna fractures of toy breed dogs.

Dynamic control of mTORC1 facilitates bone healing in mice

Bone healing requires well-orchestrated sequential actions of osteoblasts and osteoclasts. Previous studies have demonstrated that the mechanistic target of rapamycin complex 1 (mTORC1) plays a critical role in the metabolism of osteoblasts and osteoclasts. However, the role of mTORC1 in bone healing remains unclear. Here, we showed that a dynamic change in mTORC1 activity during the process was essential for proper healing and can be harnessed therapeutically for treatment of bone fractures. Low mTORC1 activity induced by osteoblastic Raptor knockout or rapamycin treatment promoted osteoblast-mediated osteogenesis, thus leading to better bone formation and shorter bone union time. Rapamycin treatment in vitro also revealed that low mTORC1 activity enhanced osteoblast differentiation and maturation. However, rapamycin treatment affected the recruitment of osteoclasts to new bone sites, thus resulting in delayed callus absorption in bone marrow cavity. Mechanistically, decreased mTORC1 activity inhibited the recruitment of osteoclast progenitor cells to healing sites through a decrease in osteoblastic expression of monocyte chemoattractant protein-1, thus inhibiting osteoclast-mediated remodeling. Therefore, normal mTORC1 activity was necessary for bone remodeling stage. Furthermore, through the use of sustained-release materials at the bone defect, we confirmed that localized application of rapamycin in early stages accelerated bone healing without affecting bone remodeling. Together, these findings revealed that the activity of mTORC1 continually changed during bone healing, and staged rapamycin treatment could be used to promote bone healing.

The Role of Mitochondrial Permeability Transition in Bone Metabolism, Bone Healing, and Bone Diseases.

Bone is a dynamic organ with an active metabolism and high sensitivity to mitochondrial dysfunction. The mitochondrial permeability transition pore (mPTP) is a low-selectivity channel situated in the inner mitochondrial membrane (IMM), permitting the exchange of molecules of up to 1.5 kDa in and out of the IMM. Recent studies have highlighted the critical role of the mPTP in bone tissue, but there is currently a lack of reviews concerning this topic. This review discusses the structure and function of the mPTP and its impact on bone-related cells and bone-related pathological states. The mPTP activity is reduced during the osteogenic differentiation of mesenchymal stem cells (MSCs), while its desensitisation may underlie the mechanism of enhanced resistance to apoptosis in neoplastic osteoblastic cells. mPTP over-opening triggers mitochondrial swelling, regulated cell death, and inflammatory response. In particular, mPTP over-opening is involved in dexamethasone-induced osteoblast dysfunction and bisphosphonate-induced osteoclast apoptosis. In vivo, the mPTP plays a significant role in maintaining bone homeostasis, with many bone disorders linked to its excessive opening. Genetic deletion or pharmacological inhibition of the over-opening of mPTP has shown potential in enhancing bone injury recovery and alleviating bone diseases. Here, we review the findings on the relationship of the mPTP and bone at both the cellular and disease levels, highlighting novel avenues for pharmacological approaches targeting mitochondrial function to promote bone healing and manage bone-related disorders.

Nicorandil-based hydrogel promotes bone defect reconstruction by targeting Hmox1

BackgroundThe local use of drugs to promote bone healing is still difficult to apply clinically. We aimed to construct a nicorandil-based hydrogel to promote local bone healing by promoting angiogenesis and inhibiting osteoclastogenesis. ResultsIn this study, we constructed a nicorandil-based hydrogel and used it to intervene in bone repair during bone defect reconstruction. The results showed that the nicorandil-based hydrogel significantly inhibited osteoclast differentiation and promoted angiogenesis in vitro. Furthermore, bone formation was significantly promoted by the use of a nicorandil-based hydrogel. Mechanistically, Hmox1 was directly targeted by nicorandil, and overexpression of Hmox1 was found to promote bone defect reconstruction. ConclusionOur study provides a fresh perspective and a potential therapeutic approach for the use of local nicorandil-based hydrogels to improve bone defect reconstruction.

Critical Literature Review of Bone Grafts and Orthobiologics for Foot and Ankle Arthrodesis to Facilitate Optimal Clinical Decision Making

Category: Basic Sciences/Biologics; Ankle Introduction/Purpose: With the extensive options of graft materials available to supplement hindfoot and ankle arthrodesis procedures, it is critical to understand the clinical evidence available, or lack thereof, before selecting a product. The purpose of this review was to summarize the available clinical evidence surrounding the utilization and efficacy of the various materials and biological agents [autologous (autograft), allogenic bone graft (allograft), demineralized bone matrix (DBM), calcium sulfate, calcium phosphate, tricalcium phosphate/hydroxyapatite, recombinant human bone morphogenetic protein -2 (rhBMP-2) or recombinant human platelet derived growth factor-BB (rhPDGF-BB)], and preparations (platelet-rich plasma or concentrated bone marrow aspirate) to promote bone healing in hindfoot and ankle procedures, with emphasis on the quality of the existing evidence to facilitate optimal clinical decision making. Methods: A literature review was performed on MEDLINE, SCOPUS, PubMed, and Google Scholar. The search was conducted in June 2023, capturing studies published in English since January 1, 2009, on patients of at least 18 years of age requiring graft material for hindfoot or ankle arthrodesis. Given the high heterogeneity in the literature and the rapidly expanding research on this topic, only comparative studies analyzing the outcomes following ankle or foot arthrodesis using different types of bone grafts were included, with primary focus on articles comparing newer biologic evidence against autograft, as the current gold standard. Results: Randomized controlled trials (RCTs), or Level I studies, for graft materials in foot and ankle arthrodesis procedures were rare and there was a lack of consistency in the time interval and definition/assessment quality of successful fusion vs. non-union or delayed union. The defined benchmark for successful fusion varied greatly, as well as the level of accuracy in the imaging method used to assess fusion (CT vs. plain radiograph). Only autograft and rhPDGF-BB/ β-TCP are investigated in multiple (≥5) RCTs, utilizing high benchmarks and quality for assessing fusion with CT scans. Overall, 24 studies were reviewed; 8 of the 24 were RCT studies, 7 studies were based on rhPDGF-BB/ β-TCP, 7 on autograft, 1 B2A study, 3 BMP-2 studies, 1 allograft, and 5 on other materials. Conclusion: There is a clear lack of high-quality evidence for most graft materials used in hindfoot and ankle fusion. Autograft is the most studied, followed by rhPDGF-BB/β-TCP. Other viable biologic agents and materials have been studied, but in lower quality comparative studies that were heterogeneous, precluding the generation of cumulative outcomes. For optimal clinical decision making, it is crucial to consider the availability of high-quality evidence, or lack of, when selecting the appropriate graft material. Future research will further investigate the role of orthobiologics and their potential to replace autograft to avoid donor site complications during hindfoot and ankle arthrodesis procedures.

Intramedullary Cylindrical Grafting for Nonunions of the Proximal Fifth Metatarsal

Fractures affecting the proximal fifth metatarsal constitute 25% of all metatarsal fractures, being particularly prevalent in sports due to stress-related incidents. Recognizing fracture patterns and implementing precise management are pivotal to mitigate potential complications, given the proclivity for suboptimal bone healing, and high incidence of nonunions (up to 4% in zone 2/3 fractures). Various methods for graft collection and application have been outlined, ranging from inlay grafts to the straightforward application of bone grafts at the nonunion site. However, the use of inlay grafts may pose challenges in size accuracy and donor site morbidity. We present and describe a novel grafting technique, which we describe as intramedullary bone grafting, exposing its capacity to promote bone healing by filling the medullary canal with cancellous bone. Developed for the treatment of delayed unions or nonunions in zone 2 and 3 fractures of the proximal fifth metatarsal, this innovative technique amalgamates the advantages of both inlay grafting and cancellous grafting. Employing a compacted cylindrical graft, tailored to match the reamed canal’s dimensions, replaces the entire medulla, facilitating the bone healing process. The technique establishes an intramedullary bone bridge across the nonunion site without compromising cortical bone integrity, extending significantly above and below the site. This presents a possible alternative to conventional methods. Furthermore, we illustrate a case involving a professional athlete with a Torg-3 fracture nonunion in zone 3, who underwent this grafting technique alongside anatomic plate fixation. Following a 4-month follow-up, a CT scan revealed complete bone healing, yielding a painless and functionally restored foot. This success enabled the athlete to resume regular practice. Level of Evidence: Level IV.