Accelerate Bone Healing Research Articles

Metabolomics provides insights into acceleration of bone healing in fractured patients with traumatic brain injuries.

While clinical surveys have frequently reported that patients with traumatic brain injuries (TBIs) and comorbidities experience faster healing, the underlying mechanisms have been investigated but remain unclear. As a comprehensive comparison and analysis of the metabolic characteristics of these two pathologies have not been undertaken, we developed a rat model of fracture and TBI and collected serum samples for metabolomic analysis using ultra-high performance liquid chromatography-quadrupole time-of-flight MS (UHPLC-Q-TOF/MS). In total, we identified 40 differential metabolites and uncovered related pathways and potential mechanisms, including aminoacyl-transfer RNA biosynthesis; differential amino acids such as leucine, cholylhistidine, aspartyl-lysine; and related lipid metabolism, and discussed their impacts on bone formation in detail. This study highlights that the UHPLC-Q-TOF/MS-based metabolomics approach offers a better understanding of the metabolic links between TBI and accelerated bone recovery.

Autologous concentrated growth factor mediated accelerated bone healing in root-end microsurgery: A multicenter randomized clinical trial

IntroductionConcentrated growth factor (CGF) is a new-generation autologous platelet concentrate that promotes tissue regeneration and has anti-inflammatory properties. This randomized multicenter trial aimed to evaluate the effects of CGF on bone healing in combination with root-end microsurgery. MethodsHealthy adult patients indicated for root-end microsurgery were randomly assigned to either the CGF or control (no CGF implantation) groups. CGF was implanted into the bone cavity after root-end filling with mineral trioxide aggregate. Clinical and periapical radiographic evaluations were conducted at 1, 3, 6, and 12 months postoperatively, with follow-up cone-beam computed tomography (CBCT) at 6 months. The lesion volume reduction rate was calculated based on data from the preoperative and follow-up CBCT images. ResultsA total of 24 patients were enrolled. The treatment success rate was 91.7% and 83.3% on 12-month periapical radiography and 6-month CBCT, respectively, without a significant difference between the two groups. The lesion volume reduction rate in the CGF group (75.6%) was significantly higher than that in the control (61.0%) group. ConclusionsAutologous CGF in conjunction with root-end microsurgery accelerated lesion reduction as observed on CBCT. Administering autologous blood products to stimulate healing in addition to removing the source of infection appears to be a promising treatment option for root-end microsurgery.

The mechanism of bone healing after traumatic brain injury

AbstractA growing body of evidence suggests that patients who experience traumatic brain injuries (TBIs) exhibit significantly shorter healing periods compared to those with isolated fractures. However, the precise underlying mechanism behind this phenomenon remains unclear. Recent studies have shed light on the potential role of hormonal signals and neural circuits originating in the hypothalamus, which play vital roles in regulating the skeletal system. Despite these advances, there is a lack of comprehensive research summarizing the crucial role of bone healing in TBIs and the underlying mechanisms. This review aimed to explore the underlying mechanisms responsible for the accelerated bone healing observed in TBI patients, with a specific focus on the intricate crosstalk between TBI and bone remodeling. Additionally, we comprehensively discuss and summarize the beneficial effects of TBI on the skeletal system and examine the TBI‐induced signaling pathways that result in accelerated fracture healing and bone remodeling. By dissecting these pathways, we aim to identify potential targets for intervention and bone repair promotion.

Reverse Dynamization Accelerates Regenerate Bone Formation and Remodeling in a Goat Distraction Osteogenesis Model.

This article was updated on December 20, 2023, because of previous errors, which were discovered after the preliminary version of the article was posted online. Figure 4 has been replaced with a figure that presents different p values. Also, on page 1943, the text that had read: "Quantitative microCT confirmed that the total volume of the regenerate in the RD group was much smaller compared with the SF (p = 0.06) and DF (p = 0.007) groups, although it was significantly smaller only compared with the DF group (Fig. 4-A). The total volume of the intact bone (contralateral tibia) was significantly smaller in the RD group compared with the other groups, but the RD group had values closest to those for the intact tibia. Similarly, the RD group had less bone volume compared with the SF and DF groups, and this value was significantly different from the DF group (p = 0.034; Fig. 4-B). Of the 3 groups, the RD group had vBMD that was the closest to that of intact bone. It also had significantly higher vBMD compared with the SF and DF groups (p < 0.0001 for both; Fig. 4-C).The results of torsional testing (Fig. 4-D) confirmed that the regenerate bone formed under conditions of RD was significantly stronger than that formed under SF or DF (p < 0.001 versus SF group, and p = 0.0493 versus DF group)."now reads: "Quantitative microCT confirmed that the total volume of the regenerate in the RD group was significantly smaller compared with the SF and DF groups (p < 0.01 for both groups; Fig. 4-A). The total volume of the intact bone (contralateral tibia) was significantly smaller compared with the SF and DF groups (p < 0.0001 for both). The RD group had values closest to those for the intact tibia, and this difference was not significant (Fig. 4-A). Similarly, the RD group had less bone volume compared with the SF and DF groups, and this value was significantly different from the DF group (p < 0.01; Fig. 4-B). Of the 3 groups, the RD group had vBMD that was the closest to that of intact bone, but the intact bone was significantly different compared with all of the other groups (p < 0.0001 for all groups). The RD group had significantly higher vBMD compared with the SF and DF groups (p = 0.042 and p = 0.046, respectively; Fig. 4-C).The results of torsional testing (Fig. 4-D) confirmed that the regenerate bone formed under conditions of RD was significantly stronger than that formed under SF or DF (p < 0.0001 versus SF group, and p = 0.0493 versus DF group). The intact group was significantly different compared with the SF group (p < 0.0001)."

Micellized protein transduction domain-bone morphogenetic protein-2 accelerates bone healing in a rat tibial distraction osteogenesis model

The clinical application of growth factors such as recombinant human bone morphogenetic protein-2 (rh-BMP-2), for functional bone regeneration remains challenging due to limited in vivo efficacy and adverse effects of previous modalities. To overcome the instability and short half-life of rh-BMP-2 in vivo, we developed a novel osteogenic supplement by fusing a protein transduction domain (PTD) with BMP-2, effectively creating a prodrug of BMP-2. In this study, we first created an improved PTD-BMP-2 formulation using lipid nanoparticle (LNP) micellization, resulting in downsizing from micrometer to nanometer scale and achieving a more even distribution. The micellized PTD-BMP-2 (mPTD-BMP-2) demonstrated improved distribution and aggregation profiles. As a prodrug of BMP-2, mPTD-BMP-2 successfully activated Smad1/5/8 and induced mineralization with osteogenic gene induction in vitro. In vivo pharmacokinetic analysis revealed that mPTD-BMP-2 had a much more stable pharmacokinetic profile than rh-BMP-2, with a 7.5-fold longer half-life. The in vivo BMP-responsive element (BRE) reporter system was also successfully activated by mPTD-BMP-2. In the in vivo rat tibia distraction osteogenesis (DO) model, micro-computed tomography (micro-CT) scan findings indicated that mPTD-BMP-2 significantly increased bone volume, bone surface, axis moment of inertia (MOI), and polar MOI. Furthermore, it increased the expression of osteogenesis-related genes, and induced bone maturation histologically. Based on these findings, mPTD-BMP-2 could be a promising candidate for the next-generation osteogenesis drug to promote new bone formation in DO surgery. Statement of SignificanceThis study introduces micellized bone morphogenetic protein-2 (mPTD-BMP-2), a next-generation osteogenic supplement that combines protein transduction domain (PTD) and nano-sized micelle formulation technique to improve transduction efficiency and stability. The use of PTD represents a novel approach, and our results demonstrate the superiority of mPTD-BMP-2 over rh-BMP-2 in terms of in vivo pharmacokinetic profile and osteogenic potential, particularly in a rat tibial model of distraction osteogenesis. These findings have significant scientific impact and potential clinical applications in the treatment of bone defects that require distraction osteogenesis. By advancing the field of osteogenic supplements, our study has the potential to contribute to the development of more effective treatments for musculoskeletal disorders.

Magnetic and Dielectric Properties of Hybrid Nanocomposites of Biologically Extracted Hydroxyapatite/Hematite/Silicon Dioxide for Potential Use in Bone Replacement Applications

Hydroxyapatite (HA) is known to be an attractive biomaterial for use in orthopedic and dental applications. Notably, acquiring HA from natural sources is an excellent step toward doing so affordably while also reducing waste. Therefore, in this study, HA was obtained from camel bones and then mixed in different proportions with silicon dioxide (SiO2) and hematite (α-Fe2O3) in order to obtain nanocomposites with distinct physical, tribo-mechanical, electrical, magnetic and biological properties. The produced powders were then examined by SEM and XRD techniques. Additionally, measurements were made of their dielectric, physical, tribo-mechanical, magnetic, and antimicrobial properties. The results revealed that successive addition of SiO2 and α-Fe2O3 reduced the porosity of the tested samples by about 3.26, 19.56, 33.69 and 51.08% which is very close to the porosity value of cortical bone. Importantly, the compressive strength of the sample with the highest percentages of SiO2 and α-Fe2O3 was 102 MPa making it similar to that of cortical bone. Also, the addition of SiO2 and α-Fe2O3 to BHA reduced its wear rate by 0.47, 13.09, 15.47, and 21.90%. Furthermore, the presence of Fe2O3 improved the magnetic and antimicrobial properties of the tested samples. The latter findings could be useful for accelerating bone healing.

An osteoinductive and biodegradable intramedullary implant accelerates bone healing and mitigates complications of bone transport in male rats.

Bone transport is a surgery-driven procedure for the treatment of large bone defects. However, challenging complications include prolonged consolidation, docking site nonunion and pin tract infection. Here, we develop an osteoinductive and biodegradable intramedullary implant by a hybrid tissue engineering construct technique to enable sustained delivery of bone morphogenetic protein-2 as an adjunctive therapy. In a male rat bone transport model, the eluting bone morphogenetic protein-2 from the implants accelerates bone formation and remodeling, leading to early bony fusion as shown by imaging, mechanical testing, histological analysis, and microarray assays. Moreover, no pin tract infection but tight osseointegration are observed. In contrast, conventional treatments show higher proportion of docking site nonunion and pin tract infection. The findings of this study demonstrate that the novel intramedullary implant holds great promise for advancing bone transport techniques by promoting bone regeneration and reducing complications in the treatment of bone defects.

Dual-Cross-Linked Magnetic Hydrogel with Programmed Release of Parathyroid Hormone Promotes Bone Healing.

Intermittent delivery of parathyroid hormone (PTH) could effectively promote bone regeneration, but the need for daily injection administration has limited its further clinical applications. Exposure to magnetic stimulation could regulate cell fate to promote osteogenesis. Herein, we developed a magnetized hydrogel with programmed PTH release and simultaneous magnetic actuation to promote osteogenic commitment. Ag dual-cross-linked hydrogel was formulated as GelMA-PVA (GP) biphasic reservoir with magnetic nanoparticles (GPM) and PTH (GPMP). Macroscopic and microscopic characterizations were performed to optimize the formulations. In vitro release assessment confirmed the programmable release of PTH with a pulsatile profile primed via magnetization in the first 4 days and a sustained release, controlled by an optimized GP matrix, for over a month. Stimulated by an alternating magnetic field, the hydrogels displayed a zigzag-shaped pulsatile release profile, and the cumulative release was enhanced by 8, 28, and 18% in In40, Ab40, and In20Ab20 (loading 40 μg PTH via incorporation, absorption, and their combination) formulations, respectively, compared with the same formulations without magnetic stimulation. An in vitro cytocompatibility test showed that all formulations were biocompatible and that PTH addition significantly promoted the proliferation of MC3T3-E1 pre-osteoblasts. In vivo studies presented enhanced new bone regeneration with significantly improved bone volume and bone mineral density in GPM and GPMP groups (increased by 120 and 251% compared with those of non-treated control), confirming their osteogenic effects and accelerated bone healing. This newly developed GPMP sample provides simultaneous osteogenesis effects via the programmed release of PTH and magnetically promoted bone regeneration and is promising in the facilitation of bone healing and treatment of various delayed/non-union conditions without the burden of daily injection.

Metformin regulates bone marrow stromal cells to accelerate bone healing in diabetic mice.

Diabetes mellitus is a group of chronic diseases characterized by high blood glucose levels. Diabetic patients have a higher risk of sustaining osteoporotic fractures than non-diabetic people. The fracture healing is usually impaired in diabetics, and our understanding of the detrimental effects of hyperglycemia on fracture healing is still inadequate. Metformin is the first-line medicine for type 2 diabetes (T2D). However, its effects on bone in T2D patients remain to be studied. To assess the impacts of metformin on fracture healing, we compared the healing process of closed-wound fixed fracture, non-fixed radial fracture, and femoral drill-hole injury models in the T2D mice with and without metformin treatment. Our results demonstrated that metformin rescued the delayed bone healing and remolding in the T2D mice in all injury models. In vitro analysis indicated that compromised proliferation, osteogenesis, chondrogenesis of the bone marrow stromal cells (BMSCs) derived from the T2D mice were rescued by metformin treatment when compared to WT controls. Furthermore, metformin could effectively rescue the impaired detrimental lineage commitment of BMSCs isolated from the T2D mice in vivo as assessed by subcutaneous ossicle formation of the BMSC implants in recipient T2D mice. Moreover, the Safranin O staining of cartilage formation in the endochondral ossification under hyperglycemic condition significantly increased at day 14 post-fracture in the T2D mice receiving metformin treatment. The chondrocyte transcript factors SOX9 and PGC1α, important to maintain chondrocyte homeostasis, were both significantly upregulated in callus tissue isolated at the fracture site of metformin-treated MKR mice on day 12 post-fracture. Metformin also rescued the chondrocyte disc formation of BMSCs isolated from the T2D mice. Taken together, our study demonstrated that metformin facilitated bone healing, more specifically bone formation and chondrogenesis in T2D mouse models.

Traumatic brain injury stimulates sympathetic tone-mediated bone marrow myelopoiesis to favor fracture healing

Traumatic brain injury (TBI) accelerates fracture healing, but the underlying mechanism remains largely unknown. Accumulating evidence indicates that the central nervous system (CNS) plays a pivotal role in regulating immune system and skeletal homeostasis. However, the impact of CNS injury on hematopoiesis commitment was overlooked. Here, we found that the dramatically elevated sympathetic tone accompanied with TBI-accelerated fracture healing; chemical sympathectomy blocks TBI-induced fracture healing. TBI-induced hypersensitivity of adrenergic signaling promotes the proliferation of bone marrow hematopoietic stem cells (HSCs) and swiftly skews HSCs toward anti-inflammation myeloid cells within 14 days, which favor fracture healing. Knockout of β3- or β2-adrenergic receptor (AR) eliminate TBI-mediated anti-inflammation macrophage expansion and TBI-accelerated fracture healing. RNA sequencing of bone marrow cells revealed that Adrb2 and Adrb3 maintain proliferation and commitment of immune cells. Importantly, flow cytometry confirmed that deletion of β2-AR inhibits M2 polarization of macrophages at 7th day and 14th day; and TBI-induced HSCs proliferation was impaired in β3-AR knockout mice. Moreover, β3- and β2-AR agonists synergistically promote infiltration of M2 macrophages in callus and accelerate bone healing process. Thus, we conclude that TBI accelerates bone formation during early stage of fracture healing process by shaping the anti-inflammation environment in the bone marrow. These results implicate that the adrenergic signals could serve as potential targets for fracture management.

Effects of Autologous Microfragmented Adipose Tissue on Healing of Tibial Plateau Levelling Osteotomies in Dogs: A Prospective Clinical Trial.

The aim of this study was to evaluate the effects of autologous microfragmented adipose tissue (MFAT) applied after mechanical fragmentation and assess these effects radiographically in bone healing in dogs subjected to tibial plateau levelling osteotomy (TPLO). Twenty dogs with unilateral cranial cruciate ligament disease were enrolled and randomly assigned to the treatment group (MFAT) or the control group (NT). The MFAT group underwent TPLO and autologous MFAT intra-articular administration, while the NT group underwent TPLO alone. Adipose tissue was collected from the thigh region, and MFAT was obtained by mechanical fragmentation at the end of the surgery. The patients were subjected to X-ray examination preoperatively, immediately postoperatively (T0), and at 4 (T1) and 8 (T2) weeks postoperatively. Two radiographic scores that had previously been described for the evaluation of bone healing after TPLO were used. A 12-point scoring system (from 0 = no healing to 12 = complete remodelling) was used at T0, T1, and T2, while a 5-point scoring system (from 0 = no healing to 4 = 76-100% of healing) was used at T1 and T2. The median healing scores were significantly higher at T1 and T2 for the MFAT group compared with the NT group for the 12-point (p < 0.05) and 5-point (p < 0.05) scoring systems. The intra-articular injection of autologous microfragmented adipose tissue can accelerate bone healing after TPLO without complications.

Recent advances on 3D-printed PCL-based composite scaffolds for bone tissue engineering.

Population ageing and various diseases have increased the demand for bone grafts in recent decades. Bone tissue engineering (BTE) using a three-dimensional (3D) scaffold helps to create a suitable microenvironment for cell proliferation and regeneration of damaged tissues or organs. The 3D printing technique is a beneficial tool in BTE scaffold fabrication with appropriate features such as spatial control of microarchitecture and scaffold composition, high efficiency, and high precision. Various biomaterials could be used in BTE applications. PCL, as a thermoplastic and linear aliphatic polyester, is one of the most widely used polymers in bone scaffold fabrication. High biocompatibility, low cost, easy processing, non-carcinogenicity, low immunogenicity, and a slow degradation rate make this semi-crystalline polymer suitable for use in load-bearing bones. Combining PCL with other biomaterials, drugs, growth factors, and cells has improved its properties and helped heal bone lesions. The integration of PCL composites with the new 3D printing method has made it a promising approach for the effective treatment of bone injuries. The purpose of this review is give a comprehensive overview of the role of printed PCL composite scaffolds in bone repair and the path ahead to enter the clinic. This study will investigate the types of 3D printing methods for making PCL composites and the optimal compounds for making PCL composites to accelerate bone healing.

Neuronal TRPV1-CGRP axis regulates bone defect repair through Hippo signaling pathway

Transient receptor potential vanilloid type 1 (TRPV1) is highly expressed on sensory neurons where it serves as a polymodal receptor for detecting physical and chemical stimuli. However, the role of TRPV1 in bone metabolism remains largely unclear. This study aimed to investigate the underlying mechanism of neuronal TRPV1 in regulating bone defect repair. In vivo experiment verified that TRPV1 activation could trigger dorsal root ganglion (DRG) producing the neuropeptide calcitonin gene-related peptide (CGRP) in mice. The accelerated bone healing of femoral defect in this process was observed compared to the control group (p < 0.05). Conversely, Trpv1 knockdown led to reduced CGRP expression in DRG and nerves innervating femur bone tissue, following impaired bone formation and osteogenic capability in the defect region (p < 0.05), which could be rescued by local CGRP treatment. In vitro, results revealed that TRPV1 function in DRG neurons contributed essentially to the regulation of osteoblast physiology through affecting the production and secretion of CGRP. The capsaicin-activated neuronal TRPV1-CGRP axis could enhance the proliferation, migration and differentiation of osteoblasts (p < 0.05). Furthermore, we found that the promoting role of neuronal TRPV1 in osteogenesis was associated with Hippo signaling pathway, reflected by the phosphorylation protein level of large tumor suppressor 1 (LATS1), MOB kinase activator 1 (MOB1) and Yes-associated protein (YAP), as well as the subcellular location of YAP. Our study clarified the effects and intrinsic mechanisms of neuronal TRPV1 on bone defect repair, which might offer us a therapeutic implication for bone disorders.

3D-printed mesoporous bioactive glass scaffolds for enhancing bone repair via synergetic angiogenesis and osteogenesis

Blood vessels play an important role in bone growth and fracture healing by providing nutrients and oxygen. Although great progress has been made in bone graft materials with good biological and physicochemical properties, vascularization of these materials remains an urgent challenge for bone regeneration. Herein, we report a novel 3D-printed mesoporous bioactive glass (MBG) scaffold (ICA/TMP@MBG) incorporating two unique extracts from Chinese medicine, namely tetramethylpyrazine (TMP) and icariin (ICA), for enhanced vascularization and bone repair. In vitro results showed that ICA/TMP@MBG could significantly upregulate VEGF secretion, thereby facilitating the formation of angiogenesis tubes in human umbilical vein endothelial cells (HUVECs). On the other hand, it can also promote the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) by stimulating the expression of OPN, ALP, OCN and BMP-2. In addition, in vivo tests further demonstrated that ICA/TMP@MBG could significantly enhance vascularization and accelerate bone healing in a mouse skull defect model. Therefore, the 3D-printed ICA/TMP@MBG has great potential to promote angiogenesis and osteogenesis in bone regeneration.

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

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. 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. 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 < 0.05). 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.

The effect of intermittent parathyroid hormone on bone lengthening: current evidence to inform future effective interventions.

Recent studies have demonstrated the positive effects of parathyroid hormone (PTH) on bone healing, and findings support the use of PTH to accelerate bone healing following distraction osteogenesis. The goal of this review was to compile and discuss the mechanisms potentially underlying the effects of PTH on newly formed bone following a bone-lengthening procedure incorporating all relevant evidence in both animal and clinical studies. This review summarized all evidence from in vivo to clinical studies regarding the effects of PTH administration on a bone-lengthening model. In addition, a comprehensive evaluation of what is currently known regarding the potential mechanisms underlying the potential benefits of PTH in bone lengthening was presented. Some controversial findings regarding the optimal dosage and timing of administration of PTH in this model were also discussed. The findings demonstrated that the potential mechanisms associated with the action of PTH on the acceleration of bone regeneration after distraction osteogenesis are involvement in mesenchymal cell proliferation and differentiation, endochondral bone formation, membranous bone formation, and callus remodeling. In the last 20 years, a number of animal and clinical studies have indicated that there is a prospective role for PTH treatment in human bone lengthening as an anabolic agent that accelerates the mineralization and strength of the regenerated bone. Therefore, PTH treatment can be viewed as a potential treatment to increase the amount of new calcified bone and the mechanical strength of the bone in order to shorten the consolidation stage after bone lengthening.

The effect of ultrasound on bone healing across a bone gap, an experimental study of a delayed union model

The aim of the study is to determine whether ultrasound accelerates bone repair across a bone gap. To replicate the clinical situation of bone repair in a severe tibial fracture, such as Gustilo grade three, we designed an experimental model to determine whether ultrasound can promote bone healing in the presence of a bone gap. The effect of ultrasound on bone healing of a tibial bone gap held in an external fixator was studied. 60 New Zealand White rabbits were divided into four groups. In one group of 6 animals, a tibial osteotomy was closed or compressed and studied at six weeks (Comparative Group). In 3 groups of 18 animals each, a tibial bone gap was maintained and was untreated, treated with ultrasound or mock ultrasound (Control Group). The repair of the bone gaps was studied in 3 animals each at 2,4,6,8,10 and 12 weeks. Investigation was by histology, angiography, radiography and densitometry. Three of the 18 untreated group progressed to delayed union, compared with 4 in the ultrasound and 3 in the mock ultrasound group (Control Group). Statistical analysis showed no difference between the three groups. 5 of the 6 closed/compressed osteotomies (Comparative Group) united faster at 6 weeks. The healing pattern of the bone gap groups were similar. We recommend this as a delayed union model. We found no evidence that ultrasound accelerated bone healing, reduced the rate of delayed union or increased callus formation in this model of delayed union. This study simulates delayed union following a compound tibial fracture and has clinical relevance concerning treatment of a delay in union with ultrasound.

MFG-E8 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells through GSK3β/β-catenin signaling pathway.

Fracture nonunion and bone defects are challenging for orthopedic surgeons. Milk fat globule-epidermal growth factor 8 (MFG-E8), a glycoprotein possibly secreted by macrophages in a fracture hematoma, participates in bone development. However, the role of MFG-E8 in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unclear. We investigated the osteogenic effect of MFG-E8 in vitro and in vivo. The CCK-8 assay was used to assess the effect of recombinant human MFG-E8 (rhMFG-E8) on the viability of hBMSCs. Osteogenesis was investigated using RT-PCR, Western blotting, and immunofluorescence. Alkaline phosphatase (ALP) and Alizarin red staining were used to evaluate ALP activity and mineralization, respectively. An enzyme-linked immunosorbent assay was conducted to evaluate the secretory MFG-E8 concentration. Knockdown and overexpression of MFG-E8 in hBMSCs were established via siRNA and lentivirus vector transfection, respectively. Exogenous rhMFG-E8 was used to verify the in vivo therapeutic effect in a tibia bone defect model based on radiographic analysis and histological evaluation. Endogenous and secretory MFG-E8 levels increased significantly during the early osteogenic differentiation of hBMSCs. Knockdown of MFG-E8 inhibited the osteogenic differentiation of hBMSCs. Overexpression of MFG-E8 and rhMFG-E8 protein increased the expression of osteogenesis-related genes and proteins and enhanced calcium deposition. The active β-catenin to total β-catenin ratio and the p-GSK3β protein level were increased by MFG-E8. The MFG-E8-induced enhanced osteogenic differentiation of hBMSCs was partially attenuated by a GSK3β/β-catenin signaling inhibitor. Recombinant MFG-E8 accelerated bone healing in a rat tibial-defect model. In conclusion, MFG-E8 promotes the osteogenic differentiation of hBMSCs by regulating the GSK3β/β-catenin signaling pathway and so, is a potential therapeutic target.

Cobalt-Doped Mesoporous Silica Coated Magnetic Nanoparticles Promoting Accelerated Bone Healing in Distraction Osteogenesis.

Large bone abnormalities are commonly treated using distraction osteogenesis (DO), but it is not suitable for a long-term application; therefore, there is an urgent need for adjuvant therapy that can accelerate bone repair. We have synthesized mesoporous silica-coated magnetic nanoparticles doped with cobalt ions (Co-MMSNs) and assessed their capacity to quicken bone regrowth in a mouse model of DO. Furthermore, local injection of the Co-MMSNs significantly accelerated bone healing in DO, as demonstrated by X-ray imaging, micro-CT, mechanical tests, histological evaluation, and immunochemical analysis. In vitro, the Co-MMSNs exhibited good biocompatibility and induced angiogenic gene expression and osteogenic development in bone mesenchymal stem cells. And the Co-MMSNs can promote bone regeneration in a rat DO model. This study demonstrated the significant potential of Co-MMSNs to shorten the DO treatment duration and effectively reduce the incidence of complications.

The Effects of Novel Pulsed Electromagnetic Field Therapy Device on Acute Distal Radius Fractures: A Prospective, Double-Blind, Sham-Controlled, Randomized Pilot Study.

this pilot study aimed at determining whether the application of a novel new method of generating pulsed electromagnetic field (PEMF), the Fracture Healing Patch (FHP), accelerates the healing of acute distal radius fractures (DRF) when compared to a sham treatment. 41 patients with DRFs treated with cast immobilization were included. Patients were allocated to a PEMF group (n = 20) or a control (sham) group (n = 21). All patients were assessed with regard to functional and radiological outcomes (X-rays and CT scans) at 2, 4, 6 and 12 weeks. fractures treated with active PEMF demonstrated significantly higher extent of union at 4 weeks as assessed by CT (76% vs. 58%, p = 0.02). SF12 mean physical score was significantly higher in PEMF treated group (47 vs. 36, p = 0.005). Time to cast removal was significantly shorter in PEMF treated patients, 33 ± 5.9 days in PEMF vs. 39.8 ± 7.4 days in sham group (p = 0.002). early addition of PEMF treatment may accelerate bone healing which could lead to a shorter cast immobilization, thus allowing an earlier return to daily life activities and work. There were no complications related to the PEMF device (FHP).