Accelerate Bone Healing Research Articles

The inhibitory effect of salidroside on RANKL-induced osteoclast formation via NFκB suppression.

Bone fractures are a prevalent clinical issue, and recent studies highlighted the promising potential of natural bone healing agents in enhancing fracture repair and regeneration. The regulatory interaction mechanism between osteoblasts and osteoclasts is crucial for bone cell biology and bone disease. In Mongolian medicine, people have used the Rhodiola rosea (R. rosea) extract to accelerate bone healing in bone fractures. Salidroside is a bioactive compound of R. rosea. Salidroside is known to regulate bone metabolism and inhibit the activation of osteoclast cells, but how it affects the differentiation of osteoclasts is unknown. We examined the effect of R. rosea extract and its bioactive compound salidroside on the RANKL-induced osteoclast formation in RAW264.7 cells. The present study observed that salidroside directly inhibits RANKL-induced TRAP-positive osteoclast formation. Immunoblotting analysis revealed that salidroside inhibited the expression of c-Fos and NFATc1, osteoclastogenic key transcription factors, by suppressing late activation of p65 NFκB. Further, the ethanol extracts of R. rosea significantly reduced the RANKL-induced osteoclasts in a dose-dependent manner. In conclusion, salidroside inhibits RANKL-induced osteoclast formation via suppressing the NFκB/c-Fos/NFATc1 signalling pathway. R. rosea, a primary source of salidroside, is helpful for bone healing via its inhibitory effect on osteoclast formation.

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.

Hydrogels as a Potential Biomaterial for Multimodal Therapeutic Applications.

Hydrogels, composed of hydrophilic polymer networks, have emerged as versatile materials in biomedical applications due to their high water content, biocompatibility, and tunable properties. They mimic natural tissue environments, enhancing cell viability and function. Hydrogels' tunable physical properties allow for tailored antibacterial biomaterial, wound dressings, cancer treatment, and tissue engineering scaffolds. Their ability to respond to physiological stimuli enables the controlled release of therapeutics, while their porous structure supports nutrient diffusion and waste removal, fostering tissue regeneration and repair. In wound healing, hydrogels provide a moist environment, promote cell migration, and deliver bioactive agents and antibiotics, enhancing the healing process. For cancer therapy, they offer localized drug delivery systems that target tumors, minimizing systemic toxicity and improving therapeutic efficacy. Ocular therapy benefits from hydrogels' capacity to form contact lenses and drug delivery systems that maintain prolonged contact with the eye surface, improving treatment outcomes for various eye diseases. In mucosal delivery, hydrogels facilitate the administration of therapeutics across mucosal barriers, ensuring sustained release and the improved bioavailability of drugs. Tissue regeneration sees hydrogels as scaffolds that mimic the extracellular matrix, supporting cell growth and differentiation for repairing damaged tissues. Similarly, in bone regeneration, hydrogels loaded with growth factors and stem cells promote osteogenesis and accelerate bone healing. This article highlights some of the recent advances in the use of hydrogels for various biomedical applications, driven by their ability to be engineered for specific therapeutic needs and their interactive properties with biological tissues.

Effect of magnesium supplementation on diaphyseal tibia fractures: a pilot study

Background: This study aimed to assess and compare the efficacy of magnesium supplementation in patients with long diaphyseal tibia fractures who have undergone surgical management with intramedullary interlocking nailing. Methods: In a prospective, randomized trial, thirty patients were included, with half receiving magnesium (420 mg/day) along with calcium (500 mg/day) supplementation for 3 months alongside surgical treatment. Radiological outcomes were evaluated through postoperative X-rays using the radiographic union scale for tibia fractures (RUST) scoring system at 6 and 12 weeks. Results: A significant difference was observed between the two groups. Patients receiving magnesium supplementation exhibited a notable improvement in RUST score, indicating an accelerated bone healing process. Conclusions: This study demonstrates the efficacy of magnesium supplementation in achieving superior radiologic outcomes compared to patients who did not receive such supplementation. The findings suggest that adjuvant magnesium supplementation could be a viable therapeutic option to enhance bone healing outcomes in individuals with tibia diaphyseal fractures.

SCUBE3 promotes osteogenic differentiation and mitophagy in human bone marrow mesenchymal stem cells through the BMP2/TGF-β signaling pathway.

In clinical settings, addressing large bone defects remains a significant challenge for orthopedic surgeons. The use of genetically modified bone marrow mesenchymal stem cells (BMSCs) has emerged as a highly promising approach for these treatments. Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) is a multifunctional secreted glycoprotein, the role of which remains unclear in human hBMSCs. This study used various experimental methods to elucidate the potential mechanism by which SCUBE3 influences osteogenic differentiation of hBMSCs invitro. Additionally, the therapeutic efficacy of SCUBE3, in conjunction with porous GeLMA microspheres, was evaluated invivo using a mouse bone defect model. Our findings indicate that SCUBE3 levels increase significantly during early osteogenic differentiation of hBMSCs, and that reducing SCUBE3 levels can hinder this differentiation. Overexpressing SCUBE3 elevated osteogenesis gene and protein levels and enhanced calcium deposition. Furthermore, treatment with recombinant human SCUBE3 (rhSCUBE3) protein boosted BMP2 and TGF-β expression, activated mitophagy in hBMSCs, ameliorated oxidative stress, and restored osteogenic function through SMAD phosphorylation. Invivo, GELMA/OE treatment effectively accelerated bone healing in mice. In conclusion, SCUBE3 fosters osteogenic differentiation and mitophagy in hBMSCs by activating the BMP2/TGF-β signaling pathway. When combined with engineered hydrogel cell therapy, it could offer valuable guidance for the clinical management of extensive bone defects.

Preoperative abaloparatide plus zoledronate treatment accelerates femoral bone healing in rats following osteotomy.

Purpose: We investigated the potential efficacy of abaloparatide (Abalo) and zoledronate (ZA) combination therapy for accelerating femoral union in a rat osteotomy model. Methods: Nine-week-old male Sprague-Dawley rats were randomly divided into four groups (n = 14 per group): control, abaloparatide (Abalo, 30μg/kg via subcutaneous injection [s.c.] 5 times per week for 6weeks), zoledronate (ZA; 0.1mg/kg via s.c., single dose), and Abalo + ZA. Rats were then subjected to unilateral osteotomy of the femoral shaft, followed by osteosynthesis with intramedullary nailing to establish bone healing models. At 2 and 4weeks after osteotomy, both femurs were removed from seven rats per group for soft X-ray imaging to evaluate bone union and microcomputed tomography (micro-CT) for bone morphometric evaluation. Blood samples were collected from all rats every 2week starting 6weeks pre- to 4weeks postosteotomy. Toluidine blue staining was used for histopathological evaluation of the undecalcified specimens. Results: Soft X-ray imaging revealed accelerated callus formation, callus maturation, and fracture line closure in Abalo and Abalo + ZA groups compared to ZA and control groups. Micro-CT demonstrated greater cortical bone and trabecular bone to total volume ratios in contralateral (left) femurs of the Abalo + ZA group compared to the Abalo group. Both trabecular and cortical bone mineral densities were also greater in contralateral femurs of the Abalo + ZA group compared to Abalo and ZA groups. Conclusion: These findings suggest substantial additive or synergistic efficacy of abaloparatide plus zoledronate combination therapy for accelerating bone healing following osteotomy and for maintaining normal bone health.

Scientific evidence available after 18 years of application of fibrin rich in platelets and leukocytes in the repair of surgical wounds: An integrative review

Introduction: In the last 18 years, Platelet and Leukocyte Rich Fibrin (L-PRF) has emerged as an innovative biomaterial in regenerative medicine and dentistry, standing out for its ability to continuously release growth factors and promote more efficient healing. However, the variability in the preparation and application of L-PRF, together with the lack of standardization, represent major challenges, increasing the need for further research to improve and standardize its clinical use. Materials and Methods: This study is an integrative review, with no need to submit it to the Research Ethics Committee. The guiding question was: “What is the main evidence in the literature on the applications of platelet- and leukocyte-rich fibrin in dentistry?”. Results and Discussion: L-PRF has proved effective in various areas of dentistry. In implantology, it accelerates bone healing and improves implant integration. In periodontics, it promotes regeneration of bone damage and improves the quality of periodontal tissue. In gingival recessions and soft tissue lesions, it accelerates regeneration and reduces post-operative discomfort. In periodontal and maxillofacial surgery, it contributes to a faster and more comfortable recovery from swelling and pain. Variability in the preparation and application of L-PRF is still a challenge, and standardization of protocols is essential to ensure more consistent and predictable results. Conclusion: After 18 years, L-PRF has shown beneficial effects in dentistry, especially in terms of bone regeneration and improved post-operative healing. However, the standardization of protocols seems to be crucial in order to improve its clinical results.

Accelerated Bone Healing via Electrical Stimulation.

Piezoelectric effect produces an electrical signal when stress is applied to the bone. When the integrity of the bone is destroyed, the biopotential within the defect site is reduced and several physiological responses are initiated to facilitate healing. During the healing of the bone defect, the bioelectric potential returns to normal levels. Treatment of fractures that exceed innate regenerative capacity or exhibit delayed healing requires surgical intervention for bone reconstruction. For bone defects that cannot heal on their own, exogenous electric fields are used to assist in treatment. This paper reviews the effects of exogenous electrical stimulation on bone healing, including osteogenesis, angiogenesis, reduction in inflammation and effects on the peripheral nervous system. This paper also reviews novel electrical stimulation methods, such as small power supplies and nanogenerators, that have emerged in recent years. Finally, the challenges and future trends of using electrical stimulation therapy for accelerating bone healing are discussed.

GO/Cu Nanosheet-Integrated Hydrogel Platform as a Bioactive and Biocompatible Scaffold for Enhanced Calvarial Bone Regeneration.

The treatment of craniofacial bone defects caused by trauma, tumors, and infectious and degenerative diseases is a significant issue in current clinical practice. Following the rapid development of bone tissue engineering (BTE) in the last decade, bioactive scaffolds coupled with multifunctional properties are in high demand with regard to effective therapy for bone defects. Herein, an innovative bone scaffold consisting of GO/Cu nanoderivatives and GelMA-based organic-inorganic hybrids was reported for repairing full-thickness calvarial bone defect. In this study, motivated by the versatile biological functions of nanomaterials and synthetic hydrogels, copper nanoparticle (CuNP)-decorated graphene oxide (GO) nanosheets (GO/Cu) were combined with methacrylated gelatin (GelMA)-based organic-inorganic hybrids to construct porous bone scaffolds that mimic the extracellular matrix (ECM) of bone tissues by photocrosslinking. The material characterizations, in vitro cytocompatibility, macrophage polarization and osteogenesis of the biohybrid hydrogel scaffolds were investigated, and two different animal models (BALB/c mice and SD rats) were established to further confirm the in vivo neovascularization, macrophage recruitment, biocompatibility, biosafety and bone regenerative potential. We found that GO/Cu-functionalized GelMA/β-TCP hydrogel scaffolds exhibited evidently promoted osteogenic activities, M2 type macrophage polarization, increased secretion of anti-inflammatory factors and excellent cytocompatibility, with favorable surface characteristics and sustainable release of Cu2+. Additionally, improved neovascularization, macrophage recruitment and tissue integration were found in mice implanted with the bioactive hydrogels. More importantly, the observations of microCT reconstruction and histological analysis in a calvarial bone defect model in rats treated with GO/Cu-incorporated hydrogel scaffolds demonstrated significantly increased bone morphometric values and newly formed bone tissues, indicating accelerated bone healing. Taken together, this BTE-based bone repair strategy provides a promising and feasible method for constructing multifunctional GO/Cu nanocomposite-incorporated biohybrid hydrogel scaffolds with facilitated osteogenesis, angiogenesis and immunoregulation in one system, with the optimization of material properties and biosafety, it thereby demonstrates great application potential for correcting craniofacial bone defects in future clinical scenarios.

Nanofibrous Microspheres: A Biomimetic Platform for Bone Tissue Regeneration.

Bone, a fundamental constituent of the human body, is a vital scaffold for support, protection, and locomotion, underscoring its pivotal role in maintaining skeletal integrity and overall functionality. However, factors such as trauma, disease, or aging can compromise bone structure, necessitating effective strategies for regeneration. Traditional approaches often lack biomimetic environments conducive to efficient tissue repair. Nanofibrous microspheres (NFMS) present a promising biomimetic platform for bone regeneration by mimicking the native extracellular matrix architecture. Through optimized fabrication techniques and the incorporation of active biomolecular components, NFMS can precisely replicate the nanostructure and biochemical cues essential for osteogenesis promotion. Furthermore, NFMS exhibit versatile properties, including tunable morphology, mechanical strength, and controlled release kinetics, augmenting their suitability for tailored bone tissue engineering applications. NFMS enhance cell recruitment, attachment, and proliferation, while promoting osteogenic differentiation and mineralization, thereby accelerating bone healing. This review highlights the pivotal role of NFMS in bone tissue engineering, elucidating their design principles and key attributes. By examining recent preclinical applications, we assess their current clinical status and discuss critical considerations for potential clinical translation. This review offers crucial insights for researchers at the intersection of biomaterials and tissue engineering, highlighting developments in this expanding field.

The Incorporation of Zinc into Hydroxyapatite and Its Influence on the Cellular Response to Biomaterials: A Systematic Review.

Zinc is known for its role in enhancing bone metabolism, cell proliferation, and tissue regeneration. Several studies proposed the incorporation of zinc into hydroxyapatite (HA) to produce biomaterials (ZnHA) that stimulate and accelerate bone healing. This systematic review aimed to understand the physicochemical characteristics of zinc-doped HA-based biomaterials and the evidence of their biological effects on osteoblastic cells. A comprehensive literature search was conducted from 2022 to 2024, covering all years of publications, in three databases (Web of Science, PUBMED, Scopus), retrieving 609 entries, with 36 articles included in the analysis according to the selection criteria. The selected studies provided data on the material's physicochemical properties, the methods of zinc incorporation, and the biological effects of ZnHA on bone cells. The production of ZnHA typically involves the wet chemical synthesis of HA and ZnHA precursors, followed by deposition on substrates using processes such as liquid precursor plasma spraying (LPPS). Characterization techniques confirmed the successful incorporation of zinc into the HA lattice. The findings indicated that zinc incorporation into HA at low concentrations is non-cytotoxic and beneficial for bone cells. ZnHA was found to stimulate cell proliferation, adhesion, and the production of osteogenic factors, thereby promoting in vitro mineralization. However, the optimal zinc concentration for the desired effects varied across studies, making it challenging to establish a standardized concentration. ZnHA materials are biocompatible and enhance osteoblast proliferation and differentiation. However, the mechanisms of zinc release and the ideal concentrations for optimal tissue regeneration require further investigation. Standardizing these parameters is essential for the effective clinical application of ZnHA.

Antiresorptive agents enhance ossification of free flap reconstructions of the mandible: a radiological retrospective cohort study.

The aim of this study was to investigate the effect of antiresorptive agents on the ossification of reconstructed mandibles by free bone grafts for the first time. A total of 38 reconstructions of the jaw were retrospectively evaluated for ossification between bone segments by two raters based on postoperative panoramic radiographs. The study group (n = 13) had segmental resection of the mandible and free bone flap reconstruction due to medication-related osteonecrosis of the jaw (MRONJ). The control group (noMRONJ, n = 25) comprised segmental mandibular resections and free bone flap reconstructions due to tumors, chronic osteomyelitis, or trauma without any radiation. Ossification time and influencing factors were evaluated. Both duration of surgery (346 ± 90min. vs. 498 ± 124min.; p < 0.001) and hospitalization (8.7 ± 2.8 days vs. 13.4 ± 5.3 days, p = 0.006) were shorter in the MRONJ group compared to the noMRONJ group. Ossification after mandibular reconstruction was significantly faster in the MRONJ study group [224 days, interquartile range (IQR) 175-287] compared to the control group (288 days, IQR 194-445; p < 0.001). Moreover, good initial contact between the segments resulted in faster ossification (p < 0.001) in the MRONJ group. Ossification rate between original and grafted bone or between grafted bone segments only did not differ in both the study and control groups (MRONJ, p = 0.705 vs. control, p = 0.292). The type of antiresorptive agent did not show any significance for ossification. The rate of wound healing disturbances did also not differ between the study and control groups (p = 0.69). Advanced MRONJ (stage 3) can be resected and reconstructed safely with free microvascular bone flaps. Antiresorptive agents enhance the ossification of the bone segments. Optimal initial contact of the bone segments accelerates bone healing. Surgery and hospitalization are markedly shortened in this vulnerable group of MRONJ patients compared to oncologic patients.

The effect of green mussel (Perna viridis) shells’ hydroxyapatite application on alkaline phosphatase levels in rabbit femur bone defect

Background Non-union fractures can be prevented with bone grafts, such as hydroxyapatite made from green mussel shells. Green mussel shells contain a high percentage of HA, making them a promising alternative for bone healing. This research aims to reveal the effectiveness of green mussel shell HA as a bone substitute material and to provide knowledge for further research. Methods This research was conducted for four months using a true experimental research method with a post-test-only control group design. This study used 36 New Zealand rabbits (Oryctolagus cuniculus) which were divided into 9 groups: positive control, negative control, and intervention at weeks 2, 4 and 6 after the intervention. All groups were subjected to three general procedures: pre-surgery, surgery, and post-surgery. This study utilized histological evaluation and biochemical assessment, specifically measuring serum alkaline phosphatase (ALP) levels, to investigate the effects of hydroxyapatite (HA) from green mussel shells on bone healing in rabbits. Results The findings demonstrated that green mussel shell HA hashad efficacy in accelerating bone healing, better than HA bovine HA i.e. green mussel shell hydroxyapatite showed superior efficacy compared to bovine hydroxyapatite in accelerating and maximizing fracture healing, as compared to the 6-week negative control group and demonstrated a significant difference (p &lt; 0.05). Conclusions Green mussel hydroxyapatite is proven to be able to fasten and maximize the bone healing process as fast as bovine HA, and even has higher efficacy than bovine HA.

Investigation of the Effects of Thymoquinone and Dental Pulp-Derived Mesenchymal Stem Cells on Tibial Bone Defect Models.

The thymoquinone obtained from Nigella sativa increases osteoblastic activity and significantly reduces the number of osteoclasts, thereby accelerating bone healing. In addition, mesenchymal stem cells isolated from various tissues are considered a potential cell source for bone regenerative therapies. The aim of this study is to investigate the effectiveness of thymoquinone, a current and novel agent, in combination with mesenchymal stem cells derived from the dental pulp in promoting bone healing. In the study, 28 male Sprague Dawley rats were used. The rats were divided into 4 groups, each consisting of 7 rats: the control group (group 1) (n=7), thymoquinone group (group 2) (n=7), stem cell group (group 3) (n=7), stem cell+thymoquinone group (group 4) (n=7). A bone defect of 4mm in diameter and 5mm in length was created in the left tibial bones of all rats with a trephine bur. In group 1, no procedure was applied to the defect area. Group 2 was applied thymoquinone (10mg/kg) with oral gavage. In group 3, stem cells were used locally to the defect area. In group 4, stem cells and thymoquinone (10mg/kg) was applied to the defect area. All rats were killed on the 28th day of the experiment. Tibia tissues extracted during sacrifice were histomorphologically examined in a fixative solution. Significant differences were found in terms of new bone formation and osteoblastic activity values in the "thymoquinone" ( P <0.05), "stem cell" ( P <0.05), and "stem cell+thymoquinone" ( P <0.05) groups compared to the "control" group. In addition, while there was no significant difference in the "thymoquinone" group compared to these stem cell+thymoquinone group in terms of osteoblastic activity ( P >0.05), the difference in terms of new bone formation was found to be significantly lower. No significant differences among the other groups were observed in new bone formation and osteoblastic activity ( P >0.05). According to the results of our study, stem cell+thymoquinone treatment for bone defects is not only more effective than thymoquinone or stem cell treatment alone but also induces greater development of bone trabeculae, contributes to the matrix and connective tissue formation, and increases the number of osteoblasts and osteocytes involved in bone formation.

Activating Angiogenesis and Immunoregulation to Propel Bone Regeneration via Deferoxamine-Laden Mg-Mediated Tantalum Oxide Nanoplatform.

Vascularization and inflammation management are essential for successful bone regeneration during the healing process of large bone defects assisted by artificial implants/fillers. Therefore, this study is devoted to the optimization of the osteogenic microenvironment for accelerated bone healing through rapid neovascularization and appropriate inflammation inhibition that were achieved by applying a tantalum oxide (TaO)-based nanoplatform carrying functional substances at the bone defect. Specifically, TaO mesoporous nanospheres were first constructed and then modified by functionalized metal ions (Mg2+) with the following deferoxamine (DFO) loading to obtain the final product simplified as DFO-Mg-TaO. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that the product was homogeneously dispersed hollow nanospheres with large specific surface areas and mesoporous shells suitable for loading Mg2+ and DFO. The biological assessments indicated that DFO-Mg-TaO could enhance the adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The DFO released from DFO-Mg-TaO promoted angiogenetic activity by upregulating the expressions of hypoxia-inducible factor-1 (HIF-1α) and vascular endothelial growth factor (VEGF). Notably, DFO-Mg-TaO also displayed anti-inflammatory activity by reducing the expressions of pro-inflammatory factors, benefiting from the release of bioactive Mg2+. In vivo experiments demonstrated that DFO-Mg-TaO integrated with vascular regenerative, anti-inflammatory, and osteogenic activities significantly accelerated the reconstruction of bone defects. Our findings suggest that the optimized DFO-Mg-TaO nanospheres are promising as multifunctional fillers to speed up the bone healing process.

CAN WE DECREASE THE HEALING INDEX (HI) DOWN TO EIGHT TO 12 DAYS/CM? AND HOW?

IntroductionFrame HI is the #Days for device removal/cm. IM Nail HI is less relevant (31–45 D/cm).Albizzia HI was 33 D/cm (1991–2003). Patients felt fine approximately 1M after end of lengthening (EoL), resuming normal life and sports. This sometimes resulted in implants fractures (e.g. skying before bone fusion). Ideally, the full fusion should occur at the EoL. We decided to shorten the HI to reach this target, optimising all parameters.Materials &amp; MethodsThe evolution of care has been monitored over a 32-year clinical experience with a fully weight-bearing nails (Albizzia then G-nail). Monitoring was with X-rays, DEXA, blood bone activity, and in London with special 5G CBCT Scans. We implemented several changes in the Care of patients and measured them according to the ‘Five Principles’ (stability, function, ‘Roads-vascular supply’, ‘Materials-calories’ and ‘Workers-BFC’, with actions on food intake, activity levels and on muscle and bone vascular growths.ResultsPreop: training (vascularity, muscle force).Op &amp; Postop: spine morphine, IM sawing preserving BFC, controlled hypo-pressure, low hydration, 50 cm leg elevation, walking, resistance bike, full motion (drainage, muscle reactivation), discharge 3–4h postop (including bilateral). Postop daily intense gym training.POD07-21: Distraction increased to fight non-linear hyper-ossification (44–50 mm gain at POD30) +/- aided by NSAIDs.HI decreased to 12–20D/cm, sometimes 8D/cm with some ‘soft fusion’ during lengthening, hardening within 1W after EoL.ConclusionsThe surgeon is not a passive X-rays observer, but has an active role in changing the healing speed and decreasing HI for patient safety. Electro/Magnetic nails (torque 1 Nm) may be clocked by bone fusion, which does not occur with the G-Nail (19 Nm).An holistic vision for patients and treatments at several levels is essential to accelerate bone healing, and to return fast to full normal life, after a short ‘lengthening parenthesis’.

The effect of mofettes and natural carbonated mineral water on accelerating bone healing in a femoral defect model in rats

Abstract: (1) Background: The aim of the study was to investigate the effecs of mofettes and car-bonated mineral water baths on bone healing using a rat femoral defect model; (2) Methods: A 2mm diameter unicortical defect in the left femoral diaphysis in 40 Wistar Rats was surgically created. Furthermore, the subjects were divided into 4 treatment-groups: control, mofette therapy, mofette therapy and carbonated mineral water bath, and carbonated mineral water bath. At the end of the 2-week treatment and at 4 and 6 weeks, the animals were evaluated through Micro-CT analysis of the bone defect and histological analysis of bone tissue and skin; (3) Results: The pro-cesses of bone consolidation and repair are not completed at 6 weeks in all groups. However, comparing the proliferated bone tissue in the created orifice and the degree of thickening of the femoral wall, it can be affirmed that at 6 weeks, the best results are present in Group 4, treated with carbonated mineral water baths, followed by the combination of mofettes and carbonated water. (4) The use of these treatments could open a new possibility for shortening the healing time in patients with bone defects, as it is non-invasive and accessible.

Major approaches of inflammatory processes and peri-implant infections in the cellular and molecular scenario of mesenchymal stem cells, exosomes, and microRNAs: a systematic review

Introduction: Bone diseases are denoted by fractures, osteoporosis, and osteoarthritis that affect a large number of individuals, with a rising prevalence of osteopenia for 64.3 million American individuals and osteoporosis for 11.9 million by the year 2030. Dental implants are not free from possible complications with consequent failure, the causes of which are still the subject of debate in the dental scientific community. In particular, peri-implant infections are multifactorial pathological conditions characterized by inflammation of the peri-implant mucosa with or without progressive loss of supporting bone. Specific expression profiles of microRNAs (miRNAs) extracted from peri-implant tissues are predictive of specific clinical outcomes of dental implants and can be used as biomarkers in implant dentistry for diagnostic and prognostic purposes. Objective: It was to address the main approaches to inflammatory processes and peri-implant infections and dental implants in the cellular and molecular scenarios of mesenchymal stem cells, exosomes, and microRNAs, emphasizing the main biomarkers in the therapeutic control of harmful dental implant processes. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from October 2023 to January 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 138 articles were found, 44 articles were evaluated in full and 34 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 26 studies with a high risk of bias and 24 studies that did not meet GRADE and AMSTAR-2. Most studies did not show homogeneity in their results, with X2=67.9%&gt;50%. It was concluded that specific expression profiles of miRNAs extracted from peri-implant tissues are predictive of specific clinical outcomes of dental implants and can be used as biomarkers in implant dentistry for diagnostic and prognostic purposes. Studies have shown that many of the miRNAs extracted from the implant's peri-crevicular fluid were common to those detected in soft tissues taken from the same peri-implant sites. Evidence suggests that exosomes derived from adipose-derived stem cells exhibit similar functions to those cells, with low immunogenicity and no tumorization. Insufficient bone volume directly impacts the placement of dental implants. Adipose-derived stem cells can accelerate bone healing when combined with dental implants. An increase in the concentration of exosomes with negative expression of miRNA-21-3p and miRNA-150-5p may be related to the development of peri-implantitis.

Nr4a1 enhances Wnt4 transcription to promote mesenchymal stem cell osteogenesis and alleviates inflammation-inhibited bone regeneration

Intense inflammatory response impairs bone marrow mesenchymal stem cell (BMSC)-mediated bone regeneration, with TGF-β1 being the most highly expressed cytokine. However, how to find effective and safe means to improve bone formation impaired by excessive TGF-β1 remains unclear. In this study, we found that the expression of orphan nuclear receptor Nr4a1, an endogenous repressor of TGF-β1, was suppressed directly by TGF-β1-induced Smad3 and indirectly by Hdac4, respectively. Importantly, Nr4a1 overexpression promoted BMSC osteogenesis and reversed TGF-β1-mediated osteogenic inhibition and pro-fibrotic effects. Transcriptomic and histologic analyses confirmed that upregulation of Nr4a1 increased the transcription of Wnt family member 4 (Wnt4) and activated Wnt pathway. Mechanistically, Nr4a1 bound to the promoter of Wnt4 and regulated its expression, thereby enhancing the osteogenic capacity of BMSCs. Moreover, treatment with Nr4a1 gene therapy or Nr4a1 agonist Csn-B could promote ectopic bone formation, defect repair, and fracture healing. Finally, we demonstrated the correlation of NR4A1 with osteogenesis and the activation of the WNT4/β-catenin pathway in human BMSCs and fracture samples. Taken together, these findings uncover the critical role of Nr4a1 in bone formation and alleviation of inflammation-induced bone regeneration disorders, and suggest that Nr4a1 has the potential to be a therapeutic target for accelerating bone healing.

Biomechanics of fracture healing: how best to optimize your construct in the OR.

Orthopaedic surgeons routinely assess the biomechanical environment of a fracture to create a fixation construct that provides the appropriate amount of stability in efforts to optimize fracture healing. Emerging concepts and technologies including reverse dynamization, "smart plates" that measure construct strain, and FractSim software that models fracture strain represent recent developments in optimizing construct biomechanics to accelerate bone healing and minimize construct failure.