Bone Healing Research Articles

Lack of nuclear localization of the Creb3l1 transcription factor causes defects in caudal fin bifurcation in zebrafish Danio rerio.

The formation of normal bone and bone healing require the cAMP-responsive element binding protein 3-like-1 (Creb3l1) transmembrane transcription factor, as deletion of the murine CREB3L1 results in osteopenic animals with limited capacity to repair bone after fracture. Creb3l1 undergoes regulated intra-membrane proteolysis (RIP) to release the N-terminal transcription activating (TA) fragment that enters the nucleus and regulates the expression of target genes. To expand our understanding of Creb3l1 role in skeletal development and skeletal patterning, we aimed to generate animals expressing only the TA fragment of Creb3l1 lacking the transmembrane domain and thereby not regulated through RIP. However, the CRISPR/Cas9-mediated genome editing in zebrafish D. rerio caused a frame-shift mutation that added 56 random amino acids at the C-terminus of the TA fragment (TA+), making it unable to enter the nucleus. Thus, TA+ doesn't regulate transcription, and the creb3l1TA+/TA+ fish animals are creb3l1 transcriptional nulls. We document that the creb3l1TA+/TA+ fish exhibit defects in the patterning of caudal fin lepidotrichia, with significantly distalized points of proximal bifurcation and decreased secondary bifurcations. Moreover, using the caudal fin amputation model, we show that creb3l1TA+/TA+ fish have decreased capacity for regeneration, and that their regenerates replicate the distalization and bifurcation defects observed in intact fins of creb3l1TA+/TA+ animals. These defects correlate with altered expression of the shha and ptch2 components of the Sonic Hedgehog signaling pathway in creb3l1TA+/TA+ regenerates. Together, our results uncover a previously unknown intersection between Creb3l1 and the Sonic Hedgehog pathway, and document a novel role of Creb3l1 in tissue patterning.

The Addition of Hydroxyapatite Nanoparticles on Implant Surfaces Modified by Zirconia Blasting and Acid Etching to Enhance Peri-Implant Bone Healing.

This study investigated the impact of adding hydroxyapatite nanoparticles to implant surfaces treated with zirconia blasting and acid etching (ZiHa), focusing on structural changes and bone healing parameters in low-density bone sites. The topographical characterization of titanium discs with a ZiHa surface and a commercially modified zirconia-blasted and acid-etched surface (Zi) was performed using scanning electron microscopy, profilometry, and surface-free energy. For the in vivo assessment, 22 female rats were ovariectomized and kept for 90 days, after which one implant from each group was randomly placed in each tibial metaphysis of the animals. Histological and immunohistochemical analyses were performed at 14 and 28 days postoperatively (decalcified lab processing), reverse torque testing was performed at 28 days, and histometry from calcified lab processing was performed at 60 days The group ZiHa promoted changes in surface morphology, forming evenly distributed pores. For bone healing, ZiHa showed a greater reverse torque, newly formed bone area, and bone/implant contact values compared to group Zi (p < 0.05; t-test). Qualitative histological and immunohistochemical analyses showed higher features of bone maturation for ZiHa on days 14 and 28. This preclinical study demonstrated that adding hydroxyapatite to zirconia-blasted and acid-etched surfaces enhanced peri-implant bone healing in ovariectomized rats. These findings support the potential for improving osseointegration of dental implants, especially in patients with compromised bone metabolism.

Inflammatory response toward a Mg-based metallic biomaterial implanted in a rat femur fracture model

The immune system plays an important role in fracture healing, by modulating the pro-inflammatory and anti-inflammatory responses occurring instantly upon injury. An imbalance in these responses can lead to adverse outcomes, such as non-union of fractures. Implants are used to support and stabilize complex fractures. Biodegradable metallic implants offer the potential to avoid a second surgery for implant removal, unlike non-degradable implants. However, considering our dynamic immune system it is important to conduct in-depth studies on the immune response to these implants in living systems. In this study, we investigated the immune response to Mg and Mg-10Gd in vivo in a rat femur fracture model with external fixation. In vivo imaging using liposomal formulations was used to monitor the fluorescence-related inflammation over time. We combine ex vivo methods with our in vivo study to evaluate and understand the systemic and local effects of the implants on the immune response. We observed no significant local or systemic effects in the Mg-10Gd implanted group compared to the SHAM and Mg implanted groups over time. Our findings suggest that Mg-10Gd is a more compatible implant material than Mg, with no adverse effects observed in the early phase of fracture healing during our 4-week study. Statement of SignificanceDegradable metallic implants in form of Mg and Mg-10Gd intramedullary pins were assessed in a rat femur fracture model, alongside a non-implanted SHAM group with special respect to the potential to induce an inflammatory response. This pre-clinical study combines innovative non-invasive in vivo imaging techniques associated with multimodal, ex vivo cellular and molecular analytics. The study contributes to the development and evaluation of degradable biometals and their clinical application potential. The study results indicate that Mg-10Gd did not exhibit any significant harmful effects compared to the SHAM and Mg groups.

Inflammatory response toward a Mg-based metallic biomaterial implanted in a rat femur fracture model

The immune system plays an important role in fracture healing, by modulating the pro-inflammatory and anti-inflammatory responses occurring instantly upon injury. An imbalance in these responses can lead to adverse outcomes, such as non-union of fractures. Implants are used to support and stabilize complex fractures. Biodegradable metallic implants offer the potential to avoid a second surgery for implant removal, unlike non-degradable implants. However, considering our dynamic immune system it is important to conduct in-depth studies on the immune response to these implants in living systems. In this study, we investigated the immune response to Mg and Mg-10Gd in vivo in a rat femur fracture model with external fixation. In vivo imaging using liposomal formulations was used to monitor the fluorescence-related inflammation over time. We combine ex vivo methods with our in vivo study to evaluate and understand the systemic and local effects of the implants on the immune response. We observed no significant local or systemic effects in the Mg-10Gd implanted group compared to the SHAM and Mg implanted groups over time. Our findings suggest that Mg-10Gd is a more compatible implant material than Mg, with no adverse effects observed in the early phase of fracture healing during our 4-week study. Statement of SignificanceDegradable metallic implants in form of Mg and Mg-10Gd intramedullary pins were assessed in a rat femur fracture model, alongside a non-implanted SHAM group with special respect to the potential to induce an inflammatory response. This pre-clinical study combines innovative non-invasive in vivo imaging techniques associated with multimodal, ex vivo cellular and molecular analytics. The study contributes to the development and evaluation of degradable biometals and their clinical application potential. The study results indicate that Mg-10Gd did not exhibit any significant harmful effects compared to the SHAM and Mg groups.

Equal rates of bone healing and reduced surgical time with iliac crest allograft compared to autograft in medial opening wedge high tibial osteotomy: a randomized controlled clinical trial.

Iliac crest autograft is frequently used to fill in bone defects after osteotomies. Nonetheless, surgery for bone autograft procurement is associated with morbidity and pain at the donor site. Alternatives to it have been explored, but there is no consensus to guide their application as a routine practice in several orthopedic procedures. Thus, this study was designed to compare the efficacy and safety between iliac crest autograft and allograft in medial opening wedge high tibial osteotomy. Forty-seven patients with a symptomatic unilateral genu varum and an indication for high tibial osteotomy were randomly assigned to receive either autograft or allograft to fill the osteotomy site. Operative time, bone healing, and complication rates (delayed union, nonunion, superficial and deep infection, loss of correction, and hardware failure) were recorded after a one-year follow-up. Data were expressed as Mean ± Standard Deviation and considered statistically significant when p < 0.05. The time to radiologic union was similar between both groups (Allograft: 2.38 ± 0.97 months vs. Autograft: 2.45 ± 0.91 months; p = 0.79). Complication rates were also similar in both groups, with one infection in the allograft group and two in the autograft group, two delayed unions in the allograft group, and three in the autograft group. The operative time differed by 11min between the groups, being lower in the allograft group (Allograft: 65.4 ± 15.1min vs. Autograft: 76.3 ± 15.2min; p = 0.02). Iliac crest allografts can be safely and effectively used in medial opening wedge high tibial osteotomy as it promotes the same rates of bone union as those achieved by autologous grafts, with the benefits of a shorter operative time. U1111-1280-0637 1 December 2022, retrospectively registered.

Total Flavonoids Isolated from the Leaves of Eucommia ulmoides Augment Peak Bone Mass in Female Rats and Show no Side Effects in Other Organs.

Eucommia ulmoides is a unique monophyletic and tertiary relict in China and is listed as a national second-class precious protected tree species. Eucommia ulmoides, recognized as a traditional Chinese medicine, can tonify the liver and kidneys and strengthen bones and muscles. Modern pharmacological research has proved that Eucommia ulmoides has multiple osteoprotective effects, including prohibiting the occurrence of osteoporosis and arthritis and enhancing the healing of bone fractures and bone defects. To check its osteotropic effects, which may provide ideas for its potential use for the development of novel drugs to treat osteoporosis, this study evaluated the effect of total flavonoids from Eucommia ulmoides leaves (TFEL) on the acquisition of Peak Bone Mass (PBM) in young female rats. TFEL was isolated, and its purity was confirmed by using a UV spectrophotometer. TFEL with a purity of 85.09% was administered to 6-week-old female rats by oral gavage at a low (50), mid (100), or high (200 mg/kg/d) dose, and the control group was administrated only with the same volume of water. After 13 weeks of treatment, the rats were sacrificed, and serum, different organs, and limb bones (femurs and tibias) were harvested, and the bone turnover markers, organ index, Bone Mineral Density (BMD), biomechanical property, and microstructure parameters were assayed. Furthermore, molecular targets were screened, and network pharmacology analyses were conducted to reveal the potential mechanisms of action of TFEL. Oral administration of TFEL for 13 weeks decreased the serum level of bone resorption marker TRACP-5b. As revealed by micro-computer tomography analysis, it elevated BMD even at a low dose (50 mg/kg/d) and improved the microstructural parameters, which were also confirmed by H&E histological staining. However, TFEL showed no effects on body weights, organ index, and micromorphology in the uterus. In our network pharmacology study, an intersection analysis screened out 64 shared targets, with quercetin, kaempferol, naringenin, and apigenin regulating the greatest number of targets associated with osteoporosis. Flavonoids in Eucommia ulmoides inhibited the occurrence of osteoporosis potentially through targeting signaling pathways for calcium, VEGF, IL-17, and NF-κB. Furthermore, AKT1, EGFR, PTGS2, VEGFA, and CALM were found to be potentially important target genes for the osteoprotective effects of flavonoids in Eucommia ulmoides. The above results suggested that TFEL can be used to elevate the peak bone mass in adolescence in female individuals, which may prevent the occurrence of postmenopausal osteoporosis, and the good safety of TFEL also suggests that it can be used as a food additive for daily life to improve the bone health.

An Injectable Hydrogel Composing Anti-Inflammatory and Osteogenic Therapy toward Bone Erosions Microenvironment Remodeling in Rheumatoid Arthritis.

Healing bone erosions in rheumatoid arthritis (RA) remains greatly challenging via biomaterial strategies. Given the unsuccessful innate bone erosion healing due to an inflammatory disorder, over-activated osteoclasts, and impaired osteoblasts differentiation, RA pathogenesis-guided engineering of an innovative hydrogel platform is needed for remodeling osteoimmune and osteogenic microenvironment of bone erosion healing. Herein, in situ adaptable and injectable interpenetrating polymer network (IPN) hydrogel is developed through an ingenious combination of a bio-orthogonal reaction between hyaluronic acid (HA) and collagen, along with effective electrostatic interactions leveraging bisphosphonate (BP)-functionalized HA macromers (HABP) and nanorod shaped zinc (Zn)-doped biphasic calcium phosphate (ZnBCP). IPN hydrogel exhibits exceptional adaptability to the local shape complexity at bone erosions, and by integrating ZnBCP and HABP, a multi-stage releasing platform is engineered, facilitating controlled cargo delivery for remodeling more anti-inflammatory M2 cells and reducing over-activated osteoclastic activities, thereby reconstructing the bone regeneration microenvironment. Sustainedly co-delivering multiple ions (calcium and phosphate) can display excellent osteogenic properties and be conducive to the bone formation process, by effects of osteogenesis-associated cell differentiation. Overall, the introduced bioactive IPN hydrogel therapy remodels the osteoimmune environment by synergistic pro-inflammation-resolving, osteogenesis, and anti-osteoclastic activities, displaying excellent bone reconstruction in the collagen-induced arthritis rabbit model.

Effect of DNA methylation on the osteogenic differentiation of mesenchymal stem cells: concise review.

Mesenchymal stem cells (MSCs) have promising potential for bone tissue engineering in bone healing and regeneration. They are regarded as such due to their capacity for self-renewal, multiple differentiation, and their ability to modulate the immune response. However, changes in the molecular pathways and transcription factors of MSCs in osteogenesis can lead to bone defects and metabolic bone diseases. DNA methylation is an epigenetic process that plays an important role in the osteogenic differentiation of MSCs by regulating gene expression. An increasing number of studies have demonstrated the significance of DNA methyltransferases (DNMTs), Ten-eleven translocation family proteins (TETs), and MSCs signaling pathways about osteogenic differentiation in MSCs. This review focuses on the progress of research in these areas.

Computational Modeling of Bone Fracture Healing Under Different Initial Conditions and Mechanical Load.

Computational model of bone healing can replace animal experiments to study the parameters affecting the bone healing process, thus reducing the damage to experimental animals and saving a lot of time. We propose a computational model for continuous simulation of four phases of bone healing to study the effects of mechanical environmental and biological factors, including initial conditions at the fracture site, mechanical stimulus loading, and vascular growth rate. A finite element model of mechanobiological fracture healing containing several pre-determined variables was developed for bone healing after fracture in sheep, which included many relevant parameters and biological effects during fracture healing, such as the effects of mechanical environment, blood supply level in the local fracture area, cell migration and diffusion, and resorption effects of fracture healing. The effects of several parameters on indices such as Young's modulus of the callus during bone healing were obtained by simulation. The initial geometry of the healing tissue and mechanical loading had the greatest effect on fracture healing, and different preset values were likely to cause delayed or non-healing fractures. Changed initial tissue properties of the healing tissue showed a nonlinear effect on fracture healing rather than a linear delay or advancement. Parameters related to angiogenesis had a greater effect on fracture healing compared to those related to cell migration. This paper quantified the effect of fracture healing pre-determined variables on fracture healing to better understand the application of mechanobiology in fracture healing simulation models and optimization of treatment strategies. The importance of initial conditions and loads on fracture healing has been shown to help physicians treat bone nonunion or delayed bone healing after a fracture.

Oral dehydroepiandrosterone supplementation enhances osteoporotic fracture healing in the OVX rats

Osteoporosis easily causes delayed fracture union, even non-union. It has been demonstrated that dehydroepiandrosterone (DHEA) supplementation can increase estrogen levels and improve bone mineral density (BMD) in the elderly, while the role of DHEA on fracture healing remains unknown. This study aimed to elucidate the impact of DHEA supplementation on osteoporotic fracture healing. Seventy-two female Sprague-Dawley rats were used. Forty-eight rats received ovariectomy (OVX), and the remaining rats received a sham OVX operation (sham group). A right transverse femoral osteotomy was performed in all rats at 12 weeks post-OVX. OVX rats were randomly allocated into 2 groups (n = 24 in each group): (i) ovariectomized rats (control group) and (ii) ovariectomized rats treated with DHEA (DHEA group, 5 mg/kg/day). The DHEA supplementation was initiated on the first day post-fracture for 3, 6, and 12 weeks. Fracture healing was evaluated by radiography, histology, biomechanical analysis, and dual-energy X-ray absorptiometry (DEXA). Serum biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA). At 3 and 6 weeks, radiographs revealed reduced calluses formation and lower radiographic scores in the control group than in other groups. The sham and DHEA groups showed higher BMD and bone mineral content (BMC) at the fracture site than the control group after fracture. Histological analysis revealed the fracture callus was remodeled better in the sham and DHEA groups than in the control group. At the early phase of healing, DHEA supplementation increased osteoblast number, callus area, and cartilage area than the control group. An increased bone area was observed in the DHEA group than in the control group at the late phase of healing. Additionally, improved biomechanical characteristics were observed in both the sham and DHEA groups than those in the control group post-fracture. ELISA showed higher levels of insulin-like growth factor-1 (IGF-1) and 17β-estradiol (E2) in the DHEA group than in the control group post-fracture. Furthermore, the DHEA group exhibited significantly elevated alkaline phosphatase (ALP) and osteocalcin (OC) levels compared to the control group at 6 and 12 weeks. The DHEA group and the control group did not exhibit a notable difference in TRAP-5b levels. The present study demonstrated that the DHEA treatment has a favorable impact on osteoporotic fracture healing by enhancing callus formation, consolidation, and strength in the OVX rats.

Identification and validation of miR-29b-3p and LIN7A as important diagnostic markers for bone non-union by WGCNA.

Bone non-union is a common fracture complication that can severely impact patient outcomes, yet its mechanism is not fully understood. This study used differential analysis and weighted co-expression network analysis (WGCNA) to identify susceptibility modules and hub genes associated with fracture healing. Two datasets, GSE125289 and GSE213891, were downloaded from the GEO website, and differentially expressed miRNAs and genes were analysed and used to construct the WGCNA network. Gene ontology (GO) analysis of the differentially expressed genes showed enrichment in cytokine and inflammatory factor secretion, phagocytosis, and trans-Golgi network regulation pathways. Using bioinformatic site prediction and crossover gene search, miR-29b-3p was identified as a regulator of LIN7A expression that may negatively affect fracture healing. Potential miRNA-mRNA interactions in the bone non-union mechanism were explored, and miRNA-29-3p and LIN7A were identified as biomarkers of skeletal non-union. The expression of miRNA-29b-3p and LIN7A was verified in blood samples from patients with fracture non-union using qRT-PCR and ELISA. Overall, this study identified characteristic modules and key genes associated with fracture non-union and provided insight into its molecular mechanisms. Downregulated miRNA-29b-3p was found to downregulate LIN7A protein expression, which may affect the healing process after fracture in patients with bone non-union. These findings may serve as a prognostic biomarker and potential therapeutic target for bone non-union.

Is smoking a risk factor for complications following total ankle arthroplasty? A meta-analysis

BackgroundSmoking has long been recognized as a risk factor for impaired wound and bone healing, particularly in the context of ankle and foot surgery. Despite numerous studies exploring the association between smoking and complications following ankle replacement, there remains significant inconsistency in their findings. Therefore, this meta-analysis study aims to elucidate whether smoking increases the rate of complications after total ankle arthroplasty (TAA), providing valuable insights for clinical management. MethodsA comprehensive systematic search was conducted in the PubMed, Embase, and Wiley databases to identify relevant English studies on the influence of smoking on postoperative complications following ankle replacement without any restrictions on publication dates. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Random-effect models were used to calculate odds ratios (OR) and 95 % confidence intervals (CI). This study adhered to PRISMA guidelines for transparent reporting and was registered with PROSPERO. ResultsThe analysis incorporated data from 12 retrospective cohort studies, totaling 17331 subjects, 2580 of whom were smokers and 791 complications following TAA. The findings revealed a statistically significant disparity in wound-related complications (OR: 2.26; 95 % CI: 1.13–4.50; P = .02), particularly evident in current smokers with an OR of 3.30 (95 % CI: 2.12–5.14; P < .00001). However, we lacked sufficient evidence to substantiate an association between smoking and complications related to the prosthesis (OR: 1.09; 95 % CI: 0.77–1.53; P = .64) or systemic complications (OR: 1.18; 95 % CI: 0.10–14.13; P = .90) following TAA. ConclusionsSmoking, especially current smoking, is associated with increased wound complication risk post-operation for total ankle arthroplasty. Despite a lack of definitive evidence on the optimal timeframe for smoking cessation before surgery, discontinuing smoking appears to be a prudent measure to mitigate these complications.

3D Printed O2-Generating Scaffolds Enhance Osteoprogenitor- and Type H Vessel Recruitment During Bone Healing

Oxygen (O2)-delivering tissue substitutes have shown tremendous potential for enhancing tissue regeneration, maturation, and healing. As O2 is both a metabolite and powerful signaling molecule, providing controlled delivery is crucial for optimizing its beneficial effects in the treatment of critical-sized injuries. Here, we report the design and fabrication of 3D-printed, biodegradable, O2-generating bone scaffold comprising calcium peroxide (CPO) that once hydrolytically activated, provides long-term generation of oxygen at a controlled, concentration-dependent manner, and polycaprolactone (PCL), a hydrophobic polymer that regulate the interaction of CPO with water, preventing burst release of O2 at early time points. When anoxic conditions were simulated in vitro, CPO-PCL scaffolds maintained the survival and proliferation of human adipose-derived stem/stromal cells (hASCs) relative to PCL-only controls. We assessed the in vivo osteogenic efficacy of hASC-seeded CPO-PCL scaffolds implanted in a non-healing critical-sized 4-mm calvarial defects in nude mice for 8 weeks. Even without exogenous osteoinductive factors, CPO-PCL scaffolds demonstrated increased new bone volume compared to PCL-only scaffolds as verified by both microcomputed tomography analysis and histological assessments. Lastly, we employed a quantitative 3D lightsheet microscopy platform to determine that O2-generating scaffolds had similar vascular volumes with slightly higher presence of CD31hiEmcnhi pro-osteogenic, type H vessels and increased number of Osterix+ skeletal progenitor cells relative to PCL-only scaffolds. In summary, 3D-printed O2 generating CPO-PCL scaffolds with tunable O2 release rates provide a facile, customizable strategy for effectively treating, craniofacial bone defects. Statement of SignificanceOxygen(O2)-delivering bone substitutes show promise in defect repair applications by supplying O2 to the cells within or around the graft, improving cell survivability and enhancing bone matrix mineralization. A novel O2-generating bone scaffold has been 3D printed for the first-time which ensures patient and defect specificity. 3D printed calcium peroxide-polycaprolactone (CPO-PCL) bone scaffold provides uninterrupted O2 supply for 22 days allowing cell survival in deprived O2 and nutrient conditions. For the first time, O2-driven bone regenerative environment in mice calvaria has been captured by light-sheet imaging which illuminates abundance of Osterix+ cells, angiogenesis at a single cell resolution indicating active site of bone remodeling and growth in the presence of O2.

Comparison of three different internal fixation methods in the treatment of femoral neck fracture

ObjectiveThis study aimed to assess the efficacy of three different fixation methods in treating femoral neck fractures in young patients. MethodsA retrospective analysis was conducted on 35 young patients with femoral neck fractures who underwent surgical treatment. Among them, 16, 12, and 7 patients underwent fixation with three cannulated compression screws (3CS), the femoral neck system (FNS), and the compound compression system (CCS), respectively. Data, including fracture classification, injury-to-surgery time, surgery duration, intraoperative blood loss, fluoroscopy instances, fracture healing time, complications, and Harris score at the final follow-up, were collected and analyzed to compare clinical outcomes among the three fixation methods. ResultsAll patients were followed for at least 6 months, exhibiting no significant differences in age, gender, injury side, fracture type, or injury-to-operation time among the three groups (P > 0.05). The FNS and CCS groups exhibited shorter operation durations and fewer intraoperative fluoroscopy instances compared to the 3CS group (P < 0.01). Despite the minimally invasive nature of 3CS, the FNS and CCS groups experienced higher intraoperative blood loss (P < 0.01). During follow-up, only one patient with 3CS fixation developed nonunion. Additionally, patients treated with 3CS demonstrated a higher incidence of femoral head necrosis and severe femoral neck shortening than the FNS and CCS groups. Excluding patients with combined nonunion, no significant difference in mean fracture healing time was observed among the three groups (P > 0.05). At the last follow-up, the FNS and CCS groups showed higher Harris scores (P < 0.05). ConclusionsBoth FNS and CCS are effective internal fixation systems for the treatment of femoral neck fractures in young patients, yielding more satisfactory clinical functional outcomes than 3CS. Comparatively, the CCS system presents a higher risk of iatrogenic rotation of the proximal fracture segment. Therefore, we advocate the insertion of two to three 2.5mm Kirschner wires from the upper edge of the femoral neck along the axial direction before CCS lag screw insertion to resist iatrogenic rotational stress.

A recent update on the fixation techniques for femoral neck fractures: A narrative review

Femoral neck fractures present significant challenges in orthopedic surgery, particularly due to technical difficulties and a high complication rate. Surgical intervention is generally recommended, with osteosynthesis and arthroplasty being the main treatment options. Osteosynthesis techniques, including dynamic hip screw (DHS), multiple cannulated screws (MCS), and the femoral neck system (FNS), aim to achieve stable fixation and facilitate fracture healing. Factors influencing the choice of osteosynthesis include fracture displacement, bone quality, patient age, and the presence of posterior tilt. While DHS offers high stability, MCS is preferred in stable type fractures with minimal invasive procedures. FNS, a newer technique, combines the advantages of DHS and MCS, providing strong fixation with minimal soft tissue damage. Considering the comprehensive findings of biomechanical and clinical studies to date, when performing osteosynthesis for unstable femoral neck fractures, caution should be exercised with MCS as it may have slightly inadequate fixation strength compared to DHS and FNS. FNS, being the newest technique, demonstrates superior fixation strength comparable to DHS and is as minimally invasive as MCS. However, it is essential to remember that long-term follow-up results are lacking for FNS.

Subtrochanteric Femur Fractures: The Association Between Obesity and Perioperative, Clinical, and Radiographic Outcomes.

To evaluate the association between obesity and treatment approaches, perioperative factors, and clinical and radiographic outcomes following subtrochanteric fracture fixation. Retrospective Cohort. Academic Medical Center. Patients operatively treated for an AO/OTA 32Axa, 32Bxa, or 32Cxa subtrochanteric femur fracture. Injury characteristics, perioperative parameters, fixation information, postoperative complications, and clinical and radiographic outcomes. Univariate analyses were conducted between the obese (BMI ≥30 kg/m2) and the nonobese (BMI <30 kg/m2) cohorts. Regression analyses were performed to assess BMI as a continuous variable. Of 230 operatively treated subtrochanteric fracture patients identified, 49 (21%) were obese and 181 (79%) were nonobese. The average age of the obese cohort was 69.6 ± 17.2 years, with 16 (33%) male and 33 (77%) female. The average age of the nonobese cohort was 71.8 ± 19.2 years, with 60 (33%) male and 121 (77%) female. Aside from BMI, there were no significant differences in demographics between the obese and nonobese (age [P = 0.465], sex [P = 0.948], American Society of Anesthesiology Score [P = 0.739]). Both cohorts demonstrated similar injury characteristics including mechanism of injury, atypical fracture type, and AO/OTA fracture pattern (32A, 32B, 32C). Obese patients underwent more open reduction procedures (59% open obese, 11% open nonobese, P < 0.001), a finding further quantified by a 24% increased likelihood of open reduction for every 1 unit increase in BMI (OR: 1.2, 95% CI, 1.2-1.3, P < 0.001). There was no difference in average nail diameter, 1 versus 2-screw nail design, or number of locking screws placed. The obese cohort was operated more frequently on a fracture table (P < 0.001) when compared with the nonobese cohort that was operated more frequently on a flat table (P < 0.001). There were no significant differences (P > 0.050) in postoperative complications, mortality/readmission rates, hospital quality measures, fixation failure, or time to bone healing. The treatment of subtrochanteric fractures in obese patients is associated with a higher likelihood of surgeons opting for open fracture reduction and the use of different operating room table types, but no difference was observed in postoperative complications, mortality or readmission rates, or healing timeline when compared with nonobese patients. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Factors influencing surgical outcomes of fixation with locking plate for three- and four-part proximal humerus fractures in patients aged 50 ​Years and older

BackgroundTreating complex three- and four-part proximal humerus fractures, especially in the elderly, remains contentious, with internal fixation using locking plates and shoulder arthroplasty being primary options. Although proximal humerus locking plates are more commonly used than shoulder replacements, they have a high complication rate. Factors like low bone density, advanced age, multiple fragment fractures, and medial cortical support loss negatively impact treatment outcomes. This study evaluates the functional and radiographic outcomes of using locking plates for treating these fractures in patients aged 50 and older, and the factors influencing outcomes and complication rates at the Ho Chi Minh City Hospital for Trauma and Orthopedics. MethodA descriptive case series study was conducted on 58 patients aged 50 and older (15 males, 43 females) with three- and four-part proximal humerus fractures. These patients underwent open reduction and internal fixation with Locking – compression plate (LCP) periarticular proximal humerus plates at the Ho Chi Minh City Hospital for Traumatology and Orthopedics (HTO) from April 2020 to April 2022. The minimum postoperative follow-up period was 12 months. ResultsThe average age of the patients was 62.78 ​± ​7.73 years, with a mean follow-up of 26.24 ​± ​5.93 months. Among them, 41 had three-part fractures (70.68 ​%) and 17 had four-part fractures (29.32 ​%). At the final follow-up (≥12 months), the mean Constant-Murley score was 70.81 ​± ​9.15, and the mean QDASH score was 8.33 ​± ​2.77. Complications occurred in 6 cases (10.34 ​%). Complex fractures, such as four-part fractures with displacement greater than 2 ​mm, had lower Constant-Murley scores and higher QDASH scores (p ​< ​0.05). Age, gender, bone density by deltoid tuberosity index (DTI), bone grafting, and rotator cuff sutures showed similar trends, but the differences were not statistically significant. ConclusionOpen reduction and internal fixation (ORIF) provides good bone healing and functional outcomes for three- and four-part proximal humerus fractures. Factors such as age, gender, bone density, bone grafting, and rotator cuff sutures do not significantly affect outcomes. Therefore, osteoporosis should not be a contraindication for ORIF with locking plates in these cases. Complex fractures, however, often lead to poorer outcomes and higher complication rates post-surgery.

Engineering a 3-dimensional tissue construct with adipose-derived stem cells for healing bone defect: An ex vivo study with femur head.

The compatibility of bone graft substitutes (BGS) with mesenchymal stem cells (MSCs) is an important parameter to consider for their use in repairing bone defects as it eventually affects the clinical outcome. In the present study, a few commercially available BGS - β-tricalcium phosphate (β-TCP), calcium sulfate, gelatin sponge, and different forms of hydroxyapatite (HAP) were screened for their interactions with MSCs from adipose tissue (ADSCs). It was demonstrated that HAP block favorably supported ADSC viability, morphology, migration, and differentiation compared to other scaffolds. The results strongly suggest the importance of preclinical evaluation of bone scaffolds for their cellular compatibility. Furthermore, the bone regenerative potential of HAP block with ADSCs was evaluated in an ex vivo bone defect model developed using patient derived trabecular bone explants. The explants were cultured for 45 days in vitro and bone formation was assessed by expression of osteogenic genes, ALP secretion, and high resolution computed tomography. Our findings confirmed active bone repair process in ex vivo settings. Addition of ADSCs significantly accelerated the repair process and improved bone microarchitecture. This ex vivo bone defect model can emerge as a viable alternative to animal experimentation and also as a potent tool to evaluate patient specific bone therapeutics under controlled conditions.

Comparison of Transoral Anterior Jefferson-Fracture Reduction Plate and Posterior Screw-Rod Fixation in C1-Ring Osteosynthesis for Unstable Atlas Fractures.

To compare the clinical outcomes of transoral anterior Jefferson-fracture reduction plate (JeRP) and posterior screw rod (PSR) surgery for unstable atlas fractures via C1-ring osteosynthesis. From June 2009 to June 2022, 49 consecutive patients with unstable atlas fractures were treated by transoral anterior JeRP fixation (JeRP group) or PSR fixation (PSR group) and followed up at General Hospital of Southern Theatre Command of PLA; 30 males and 19 females were included. The visual analogue scale (VAS) score, Neck Disability Index (NDI), distance to anterior arch fracture (DAAF), distance to posterior arch fracture (DPAF), lateral mass displacement (LMD), Redlund-Johnell value, postoperative complications, and fracture healing rate were retrospectively collected and statistically analyzed. Compared with that in the PSR group, the bleeding volume in the JeRP group was lower, and the length of hospital stay was longer. The VAS scores and NDIs of both groups were significantly improved after surgery. The postoperative DAAF and DPAF were significantly smaller after surgery in both groups. Compared with the significantly shorter DPAF in the PSR group, the JeRP group had a smaller DAAF, shorter LMDs and larger Redlund-Johnell value postoperatively and at the final follow-up. The fracture healing rate at 3 months after surgery was significantly greater in the JeRP group (p < 0.05). Both C1-ring osteosynthesis procedures for treating unstable atlas fractures yield satisfactory clinical outcomes. Transoral anterior JeRP fixation is more effective than PSR fixation for holistic fracture reduction and short-term fracture healing, but the hospital stay is longer.

Optimizing immunofluorescent staining of H vessels within an irradiated fracture callus in paraffin-embedded tissue samples

ABSTRACT H vessels are an essential link in angiogenic-osteogenic coupling and orchestrate the process of bone healing. H vessels are critically deficient in the setting of radiation-induced fractures, which have been reported to occur in up to 25% of patients undergoing radiotherapy. By increasing H-vessel proliferation, Deferoxamine (DFO) revitalizes the physiologic response to skeletal injury and accelerates irradiated fracture repair. H-vessel quantification is therefore an important outcome measure in histologic analysis of bone healing. However, an optimized protocol for staining H vessels in formalin-fixed paraffin-embedded (FFPE) tissue sections has not been reported. With this protocol, we describe a method of staining FFPE bone samples with minimal background fluorescence and high signal-to-noise ratio. We examined mandibular specimens in a rat model of bone healing from a range of fracture conditions, including healthy bone (Fx), irradiated bone (XFx), and irradiated bone with DFO treatment (XFx-DFO). Quantitative analysis revealed a significant increase of H vessels in the XFxDFO group compared to both the Fx and XFx groups. By optimizing immunofluorescent staining of H vessels in FFPE samples across a range of fracture conditions, we offer investigators an efficacious means of producing reliable imaging for quantitative analysis of H vessels in an irradiated fracture callus.