PPARγ inhibition promotes osteogenic differentiation of bone marrow mesenchymal stem cells and fracture healing.

This study aimed to explore the effects of peroxisome proliferator-activated receptor γ (PPARγ) inhibition on fracture healing of nonunion and the underlying mechanisms. Bone marrow mesenchymal stem cells (BMSCs) were treated with PPARγ antagonist GW9662 (5 µM, 10 µM). Alkaline phosphatase (ALP) staining and Alizarin Red S was used to assess early stage of osteogenesis and osteogenic differentiation. GW9662 (1 mg/kg/day) were administered intraperitoneally into the rats with bone fracture. Bone healing processes in the rat femur fracture model were recorded and assessed by radiographic methods on Weeks 8, 14, and 20 postoperation. Osteogenesis and angiogenesis at the fracture sites were evaluated by radiographic and histological methods on postoperative Week 20. GW9662 treatment increased ALP activity and Alp mRNA expression in rat BMSCs. Moreover, GW9662 administration increased matrix mineralization and mRNA and protein levels of Bmp2 and Runx2 in the BMSCs. In addition, GW9662 treatment improved radiographic score in the fracture rats and increased osteogenesis-related proteins, including type I collagen, osteopontin, and osteoglycin, in the bone tissues of the fracture sites. In conclusion, PPARγ inhibition promotes osteogenic differentiation of rat BMSCs, as well as improves the fracture healing of rats through Bmp2/Runx2 signaling pathway in the rat model of bone fracture.

Polyene phosphatidylcholine promotes tibial fracture healing in rats by stimulating angiogenesis dominated by the VEGFA/VEGFR2 signaling pathway.

One of the factors that predispose to fractures is liver damage. Interestingly, fractures are sometimes accompanied by abnormal liver function. Polyene phosphatidylcholine (PPC) is an important liver repair drug. We wondered if PPC had a role in promoting fracture healing. A rat model of tibial fracture was developed using the modified Einhorn model method. X-rays were used to detect the progression of fracture healing. Progress of ossification and angiogenesis at the fracture site were analyzed by Safranin O/fast green staining and CD31 immunohistochemistry. To investigate whether PPC has a direct angiogenesis effect, HUVECs were used. We performed MTT, wound healing, Transwell migration, and tube formation assays. Finally, RT-qPCR and Western blot analysis were used to study the underlying mechanism. The results showed that PPC significantly shortened the apparent recovery time of mobility in rats. PPC treatment significantly promoted the formation of cartilage callus, endochondral ossification, and angiogenesis at the fracture site. In vitro, PPC promoted the proliferative viability of HUVECs, their ability to heal wounds, and their ability to penetrate membranes in the Transwell apparatus and increased the tube formation of cells. The transcription of VEGFA, VEGFR2, PLCγ, RAS, ERK1/2 and MEK1/2 was significantly up regulated by PPC. Further, the protein level results demonstrated a significant increase in the expression of VEGFA, VEGFR2, MEK1/2, and ERK1/2 proteins. In conclusion, our findings suggest that PPC promotes angiogenesis by activating the VEGFA/VEGFR2 and downstream signaling pathway, thereby accelerating fracture healing.

Impact of osteoporosis and osteoporosis medications on fracture healing: a narrative review.

Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing. BACKGROUND: Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing. METHODS: Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT). RESULTS: Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans. CONCLUSION: Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved.

Teriparatide Does not Have Beneficial Effects on Bone Healing in Complete Atypical Femur Fractures.

Teriparatide is an anabolic drug sometimes administered to patients who have atypical femoral fracture (AFF). However, whether teriparatide has beneficial effects on bone healing remains uncertain. The present study aimed to analyze the association between teriparatide and bone healing in complete AFF. A total of 59 consecutive cases (58 patients) who underwent intramedullary nailing for complete AFF were categorized based on postoperative use of teriparatide into the non-teriparatide (non-TPTD, n = 34) and teriparatide groups (TPTD, n = 25). Time-to-bone union was evaluated and compared between the two groups. Additionally, multiple regression analysis was performed to evaluate factors affecting time-to-bone union. All participants were women, with a mean age of 77.6 years (range: 62-92). No significant difference in time-to-bone union was found between the non-TPTD and TPTD groups (5.5 months vs. 5.8 months, p = 0.359). Two patients in the non-TPTD group underwent reoperation (p = 0.503) due to failure caused by inadequate fixation, and both achieved bone healing after additional fixation with blocking screws. Multiple regression analysis revealed that the anterior gap of the fracture site postoperatively was a factor affecting time-to-bone union (p = 0.014). The beneficial effect of teriparatide on bone healing in complete AFF could not be confirmed. Additional randomized controlled trials are required. Nonetheless, appropriate techniques, including efforts to reduce the gap on the tensile side during the surgery, are important for reliable bone healing.

Plasminogen activator inhibitor-1 is involved in glucocorticoid-induced decreases in angiogenesis during bone repair in mice.

INTRODUCTION: Glucocorticoids delay fracture healing and induce osteoporosis. Angiogenesis plays an important role in bone repair after bone injury. Plasminogen activator inhibitor-1 (PAI-1) is the principal inhibitor of plasminogen activators and an adipocytokine that regulates metabolism. However, the mechanisms by which glucocorticoids delay bone repair remain unclear. MATERIALS AND METHODS: Therefore, we herein investigated the roles of PAI-1 and angiogenesis in glucocorticoid-induced delays in bone repair after femoral bone injury using PAI-1-deficient female mice intraperitoneally administered dexamethasone (Dex). RESULTS: PAI-1 deficiency significantly attenuated Dex-induced decreases in the number of CD31-positive vessels at damaged sites 4 days after femoral bone injury in mice. PAI-1 deficiency also significantly ameliorated Dex-induced decreases in the number of CD31- and endomucin-positive type H vessels and CD31-positive- and endomucin-negative vessels at damaged sites 4 days after femoral bone injury. Moreover, PAI-1 deficiency significantly mitigated Dex-induced decreases in the expression of vascular endothelial growth factor as well as hypoxia inducible factor-1α, transforming growth factor-ß1, and bone morphogenetic protein-2 at damaged sites 4 days after femoral bone injury. CONCLUSION: The present results demonstrate that Dex-reduced angiogenesis at damaged sites during the early bone-repair phase after femoral bone injury partly through PAI-1 in mice.

mPPTMP195 nanoparticles enhance fracture recovery through HDAC4 nuclear translocation inhibition.

Delayed repair of fractures seriously impacts patients' health and significantly increases financial burdens. Consequently, there is a growing clinical demand for effective fracture treatment. While current materials used for fracture repair have partially addressed bone integrity issues, they still possess limitations. These challenges include issues associated with autologous material donor sites, intricate preparation procedures for artificial biomaterials, suboptimal biocompatibility, and extended degradation cycles, all of which are detrimental to bone regeneration. Hence, there is an urgent need to design a novel material with a straightforward preparation method that can substantially enhance bone regeneration. In this context, we developed a novel nanoparticle, mPPTMP195, to enhance the bioavailability of TMP195 for fracture treatment. Our results demonstrate that mPPTMP195 effectively promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts while inhibiting the differentiation of bone marrow mononuclear macrophages into osteoclasts. Moreover, in a mouse femur fracture model, mPPTMP195 nanoparticles exhibited superior therapeutic effects compared to free TMP195. Ultimately, our study highlights that mPPTMP195 accelerates fracture repair by preventing HDAC4 translocation from the cytoplasm to the nucleus, thereby activating the NRF2/HO-1 signaling pathway. In conclusion, our study not only proposes a new strategy for fracture treatment but also provides an efficient nano-delivery system for the widespread application of TMP195 in various other diseases.

Macrophage membrane-reversibly camouflaged nanotherapeutics accelerate fracture healing by fostering MSCs recruitment and osteogenic differentiation.

The fracture healing outcome is largely dependent on the quantities as well as osteogenic differentiation capacities of mesenchymal stem cells (MSCs) at the lesion site. Herein, macrophage membrane (MM)-reversibly cloaked nanocomplexes (NCs) are engineered for the lesion-targeted and hierarchical co-delivery of short stromal derived factor-1α peptide (sSDF-1α) and Ckip-1 small interfering RNA (Ckip-1 siRNA, siCkip-1) to promote bone repair by concurrently fostering recruitment and osteogenic differentiation of endogenous MSCs. To construct the NCs, a membrane-penetrating α-helical polypeptide first assembles with siCkip-1, and the cationic NCs are sequentially coated with catalase and an outer shell of sSDF-1α-anchored MM. Due to MM-assisted inflammation homing, intravenously injected NCs could efficiently accumulate at the fractured femur, where catalase decomposes the local hydrogen peroxide to generate oxygen bubbles that drives the shedding of sSDF-1α-anchored MM in the extracellular compartment. The exposed, cationic inner core thus enables robust trans-membrane delivery into MSCs to induce Ckip-1 silencing. Consequently, sSDF-1α-guided MSCs recruitment cooperates with siCkip-1-mediated osteogenic differentiation to facilitate bone formation and accelerate bone fracture healing. This study provides an enlightened strategy for the hierarchical co-delivery of macromolecular drugs into different cellular compartments, and it also renders a promising modality for the management of fracture healing.

Osthole accelerates osteoporotic fracture healing by inducing the osteogenesis-angiogenesis coupling of BMSCs via the Wnt/ß-catenin pathway.

Osthole, a natural coumarin derivative, has been shown to have multiple pharmacological activities. However, its effect on osteoporotic fracture has not yet been examined. This research was designed to explore the unknown role and potential mechanism of osthole on osteoporotic fracture healing. We first evaluated the osteogenic and angiogenic abilities of osthole. Then angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis, and further explore its molecular mechanism. After that, we established osteoporotic fracture model in ovariectomy-induced osteoporosis rats and treated the rats with osthole or placebo. Radiography, histomorphometry, histology, and sequential fluorescent labeling were used to evaluate the effect of osthole on osteoporotic fracture healing. In vitro research revealed that osthole promoted osteogenesis and up-regulated the expression of angiogenic-related markers. Further research found that osthole couldn't facilitate the angiogenesis of human umbilical vein endothelial cells in a direct manner, but it possessed the ability to induce the osteogenesis-angiogenesis coupling of bone marrow mesenchymal stem cells (BMSCs). Mechanistically, this was conducted through activating the Wnt/ß-catenin pathway. Subsequently, using ovariectomy-induced osteoporosis tibia fracture rat model, we observed that osthole facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation. Sequential fluorescent labeling confirmed that osthole could effectively accelerate bone formation in the fractured region. The data above indicated that osthole could accelerate osteoporotic fracture healing by inducing the osteogenesis-angiogenesis coupling of BMSCs via the Wnt/ß-catenin pathway, which implied that osthole may be a potential drug for treating osteoporosis fracture.

The Role of Botulinum Neurotoxin A in the Conservative Treatment of Fractures: An Experimental Study on Rats.

This paper explores the role of botulinum neurotoxin in aiding fracture recovery through temporary muscle paralysis. Specifically, it investigates the effects of botulinum neurotoxin-induced paralysis of the sternocleidomastoid muscle on clavicle fractures in rats. The research aims to assess safety, effectiveness, and the impact on fracture healing. Healthy male Albino Wistar rats were divided into four groups: clavicle fracture, botulinum neurotoxin injection, both, and control. Surgeries were conducted under anaesthesia, and postoperatively, animals were monitored for 28 days. Euthanasia and radiological assessment followed, examining fracture healing and muscle changes, while tissues were histopathologically evaluated. The modified Lane-Sandhu scoring system was used for the radiographic evaluation of clavicle fractures, and the results varied from complete healing to nonunion. Histopathological examination at 28 days postfracture showed fibrous tissue, mesenchymal cells, and primary callus formation in all groups. Despite varied callus compositions, botulinum neurotoxin administration did not affect clavicle healing, as evidenced by similar scores to the control group. Several studies have explored botulinum neurotoxin applications in fracture recovery. Research suggests its potential to enhance functional recovery in certain types of fractures. Theoretical benefits include managing muscle spasticity, aiding reduction techniques, and preventing nonunion. However, botulinum neurotoxin's transient effect and nonuniversal applications should be considered. The present study found that botulinum toxin had no clear superiority in healing compared to controls, while histological evaluation showed potential adverse effects on muscle tissue. Further research is essential to understand its risk-benefit balance and long-term effects.

The effect of teriparatide on patients with atypical femur fractures: a systematic review and meta-analysis.

INTRODUCTION: Bisphosphonates (BPs) are one of the most often used drugs to lower fracture risk in osteoporosis patients; nonetheless, BPs have been linked to atypical femoral fracture (AFF). Teriparatide (TPTD) is a parathyroid hormone analogue and anabolic drug that may accelerate fracture repair. TPTD has been considered as a possible treatment for AFF, particularly those caused by BP use. We evaluate the effect of TPTD on AFF in this systematic review and meta-analysis. MATERIALS AND METHODS: A thorough search of: Web of Science, Scopus, PubMed, and Cochrane was conducted on August 2, 2023. Trials evaluating the effect of TPTD on the incidence of: complete bone healing, non-union, early and delayed bone union, progression of incomplete AFF to complete AFF, and time to bone union were included. Using Review Manager (RevMan) version 5.4, the risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence interval (CI) were estimated for dichotomous and continuous outcomes, respectively. The Newcastle-Ottawa Scale was used to assess the quality of studies. RESULTS: Eight studies met the eligibility criteria and were included in our analysis. TPTD significantly increased the incidence of early bone union (RR = 1.45, 95% CI [1.13, 1.87], P = 0.004) and time to bone union (MD = -1.56, 95% CI [-2.86, -0.26], P = 0.02) compared to the control group. No significant differences were observed in terms of complete bone healing (RR = 1.09, 95% CI [0.99, 1.13], P = 0.12), non-union (RR = 0.48, 95% CI [0.22, 1.04], P = 0.06), and progression of incomplete AFF to complete AFF (RR = 0.27, 95% CI [0.04, 1.97], P = 0.19). CONCLUSIONS: TPTD is an effective therapy for enhancing and hastening healing following AFF, particularly in postoperative settings. Future large randomized clinical trials are needed to confirm or dispute the results.

Does vanillic acid affect fracture healing? An experimental study in a rat model of femur fracture.

BACKGROUND AND OBJECTIVES: We aimed to determine the effects of vanillic acid (VA) on fracture healing radiologically, histologically, immunohistochemically, and biomechanically using a rat femur open fracture injury model. METHODS: 32 male Wistar-Albino rats were used and divided into two groups: the study group (VA) and the control group. From the time they were operated on until they were sacrificed, the rats in the study group were given 100 mg/kg/day VA by oral gavage. After sacrification, the femurs were analyzed. RESULTS: It was observed that the Huo histological scoring was significantly higher in the VA group (p = 0.001), and the ratio of the amount of callus tissue compared to intact bone tissue was significantly higher. While no significant difference was observed in immunohistochemical H-scores in ColI antibody staining (p = 1.000), a borderline significant difference in favor of VA was observed in ColIII antibody staining (p = 0.078). In biomechanical analysis, failure load (N), total energy (J), maximum stress (MPa), and stiffness (N/mm) measurements were significantly higher in the VA group (p = 0.040, p = 0.021, p = 0.015, and p = 0.035, respectively). CONCLUSION: It has been observed that VA, with its antioxidative properties, increases fracture healing in rats, in which an open fracture model was created. We are hopeful that such an antioxidant, which is common in nature, will increase fracture healing. Since this study is the first to examine the effect of VA on fracture healing, further studies are needed.

Effectiveness of teriparatide in in improving healing rates and bone-turnover markers of osteoporotic hip fracture: a meta-analysis.

Objective: To evaluate the effect of subcutaneous teriparatide therapy on fracture healing rate and change in bone mass density in osteoporotic hip fractures. METHODS: The meta-analysis was done from September to December 2022, and comprised literature search on Wanfang, CNKI, VIP, PubMed, Embase, Cochrane Library, and Web of Science databases from the establishment of the respective database till December 2022. The relevant journals of the library of Macao University of Science and Technology, China, were manually searched for randomised controlled trials of teriparatide in the treatment of osteoporotic hip fractures. The shortlisted studies were subjectd to Cochrane Risk of Bias tool and the Jadad Rating Scale. Meta-analysis was done using the RevMan 5.4 software provided by the Cochrane Collaboration Network. Fracture healing rate and bone mineral density were the primary outcome measures, while mortality, adverse events, malformations, complications, subsequent fractures, timed-up-and-go test, visual analogue scale score, and procollagen type I N-terminal propeptide were the secondary outcome measures. RESULTS: Of the 1,094 articles retrieved, 8(0.7%) randomised controlled trials were analysed. There were 744 patients; 372(50%) in the teriparatide group and 372(50%) in the control group. Fracture healing rate was not significantly different (p=0.82), while bone mineral density was significantly different between the groups (p<0.001). Mortality, adverse events, deformity, and complications were not significantly different (p>0.05), while subsequent fractures, timed-up-and-go score, visual analogue scale score and procollagen type I N-terminal propeptide were significantly different between the groups (p<0.05). Conclusion: The literature did not support teriparatide's ability to improve the healing rate of osteoporotic hip fractures, or to reduce mortality, adverse events, malformations, and complications. In addition, teriparatide could increase bone mineral density of osteoporotic hip fractures and the procollagen type I N-terminal propeptide value, alleviate hip pain, and reduce subsequent fracture rates. This trial is registered with PROSPERO with registration number CRD42022379832.

The effect of favipiravir on fracture healing.

The aim of this study was to evaluate the effects of favipiravir on fracture healing. Forty-eight female rats which had a femur fracture with intramedullary Kirschner wire fixation performed were divided into 6 groups; 2 control groups (C1, C2) and 4 experimental groups (F1, F2, F3, F4). The control groups (C1, C2) received physiological saline by oral gavage for 14 days. Two of the experimental groups (F1, F2) received favipiravir by oral gavage for 5 days, whereas the other groups (F3, F4) received it for 14 days. C1, F1 and F3 groups were sacrificed and evaluated on the 14th day, and C2, F2 and F4 groups were sacrificed and evaluated on the 28th day. The fracture sites were assessed for healing radiologically using the Lane and Sandhu scoring system, and assessed histologically using the Huo et al. scoring system. There was no difference between the groups regarding radiological and histological evaluations made on the 14th day (P > .05, P=.216, respectively). On the 28th day, the radiological scores were found to be significantly higher in the control group when compared to the experimental groups (P < .05). Histologically, the control group demonstrated better fracture healing than the groups that had favipiravir administered (P < .001). This study has shown that favipiravir can have negative effects on fracture healing both radiologically and histologically.

Evaluation of recombinant human erythropoietin as a promoter of bone healing in cats with femoral fractures.

Background: The bone regeneration potential of erythropoietin (EPO) is not yet fully investigated, but some previous experimental studies demonstrated that its application activated the differentiation of osteoblasts and promoted bone formation. Aim: The aim of the present study was to evaluate the effects of recombinant human erythropoietin (rhEpo) on bone healing in cats with fragmented long bone fractures. Methods: Twelve cats were divided into two groups-control (n = 6) in which physiological saline was applied at the fracture gap site and EPO (n = 6) with the application of 1,000 IU rhEpo. The effects of EPO on blood erythrocyte counts, hemoglobin content, and hematocrit were monitored by serial complete blood cell tests, whereas bone formation was evaluated by clinical and radiographic examinations on post-operative weeks 1, 2, 3, 4, 6, and 8. Results: All tested blood parameters were within the reference range. A faster fracture healing and full limb weight-bearing were observed in the EPO group, with statistically significant differences with respect to the control group. Conclusion: The obtained results confirmed that the local application of rhEpo promoted bone healing in cats with fragmented femoral fractures and increased bone callus strength without having significant systemic effects.

Can silver nanoparticles stabilized by Fenugreek (Trigonella foenm -graecum) improve tibial bone defects repair in rabbits? A preliminary study.

Background: A fracture is considered a medical emergency leading to considerable complications. Aim: This study aimed to describe the accelerating action of Ag-NPs-FG on fracture healing in rabbits. Methods: Silver NPs (AgNPs) were reduced with fenugreek (FG), loaded into a starch gel base, and investigated for their morphology, size, and charge. Four equal groups were randomly formed of 40 adult male rabbits. A 3.5 mm diameter bone defect was created at the proximal metaphysis of the right tibia in each rabbit. Groups 1-4 were injected with placebo saline, AgNPs-FG, plain gel, and FG-gel at the bone defect zone, respectively. The healing was assessed for 8 weeks postoperatively based on the radiographic, bone turnover markers, and histopathological examinations. Results: The AgNPs-FG was obtained as a faint reddish color, spherical in shape, with an absorbance of 423 nm, a size of 118.0 ± 1.7 nm, and a surface charge of -7.8 ± 0.518 mV. The prepared AgNPs-FG hydrogel was clear, translucent, and homogenous. The pH values were 6.55-6.5 ± 0.2, the viscosity of 4,000 and 1,875 cPs, and spreadability of 1.6 ± 0.14 and 2.0 ± 0.15 for both FG and AgNPs-FG hydrogel, respectively. The radiographic union scale was significantly (p < 0.05) improved in group 2 with a significant (p < 0.05) increase in bone turnover markers was found in comparison to other treated groups. Histopathological examination revealed the formation of mature bone on the 28th postoperative day in groups 2 and 4. Conclusion: Colloidal nano-formulation of AgNPs-FG loaded hydrogel could be a promising formulation to accelerate rabbits' tibial bone healing process.

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 17ß-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.

Titanium vs PEO Surface-Modified Magnesium Plate Fixation in a Mandible Bone Healing Model in Sheep.

Titanium plates are the current gold standard for fracture fixation of the mandible. Magnesium alloys such as WE43 are suitable biodegradable alternatives due to their high biocompatibility and elasticity modulus close to those of cortical bone. By surface modification, the reagibility of magnesium and thus hydrogen gas accumulation per time are further reduced, bringing plate fixation with magnesium closer to clinical application. This study aimed to compare bone healing in a monocortical mandibular fracture model in sheep with a human-standard size, magnesium-based, plasma electrolytic-oxidation (PEO) surface modified miniplate fixation system following 4 and 12 weeks. Bone healing was analyzed using micro-computed tomography and histological analysis with Movat's pentachrome and Giemsa staining. For evaluation of the tissue's osteogenic activity, polychrome fluorescent labeling was performed, and vascularization was analyzed using immunohistochemical staining for alpha-smooth muscle actin. Bone density and bone mineralization did not differ significantly between titanium and magnesium (BV/TV: T1: 8.74 ± 2.30%, M1: 6.83 ± 2.89%, p = 0.589 and T2: 71.99 ± 3.13%, M2: 68.58 ± 3.74%, p = 0.394; MinB: T1: 26.16 ± 9.21%, M1: 22.15 ± 7.99%, p = 0.818 and T2: 77.56 ± 3.61%, M2: 79.06 ± 4.46%, p = 0.699). After 12 weeks, minor differences were observed regarding bone microstructure, osteogenic activity, and vascularization. There was significance with regard to bone microstructure (TrTh: T2: 0.08 ± 0.01 mm, M2: 0.06 ± 0.01 mm; p = 0.041). Nevertheless, these differences did not interfere with bone healing. In this study, adequate bone healing was observed in both groups. Only after 12 weeks were some differences detected with larger trabecular spacing and more vessel density in magnesium vs titanium plates. However, a longer observational time with full resorption of the implants should be targeted in future investigations.

Promoting a Cobalt Complex of Qingzhuan Dark Tea Polysaccharides on Fracture Healing in Rats.

Fractures occur commonly with multiple injuries, and their incidence has increased in recent years. Trace amounts of cobalt are necessary for many living organisms as it stimulates hematopoiesis and improves bone health. However, cobalt is also toxic, as it might cause allergic reactions and tissue destruction. These factors limit the application of cobalt in some medical fields. We studied the tea polysaccode-cobalt complex (TPS-Co) prepared from Qingzhuan Dark Tea polysaccharides. We used 6-week-old Sprague-Dawley rats to establish a femoral fracture model and evaluated the effects of CoCl2 and TPS-Co on the healing of femoral fractures. In this study, treatment with TPS-Co for the same content of cobalt intake decreased the side effects associated with CoCl2 treatment and accelerated the healing of femoral fractures in rats. This treatment method promoted angiogenesis by upregulating the expression of vascular endothelial growth factor and hypoxia-inducible factor. Bone formation was promoted via the upregulation of the expression of bone morphogenetic protein 2 and serum bone alkaline phosphatase. TPS-Co was found to actively regulate bone and vascular systems, resulting in significant bone regeneration effects. Therefore, the Qingzhuan Dark Tea polysaccharide cobalt complex might be used as an additive or drug to promote fracture healing, and thus, it might have a huge market value.

A rhPDGF-BB/bovine type I collagen/ß-TCP mixture for the treatment of critically sized non-union tibial defects: An in vivo study in rabbits.

Non-union during healing of bone fractures affects up to ~5% of patients worldwide. Given the success of recombinant human platelet-derived growth factor-B chain homodimer (rhPDGF-BB) in promoting angiogenesis and bone fusion in the hindfoot and ankle, rhPDGF-BB combined with bovine type I collagen/ß-TCP matrix (AIBG) could serve as a viable alternative to autografts in the treatment of non-unions. Defects (~2 mm gaps) were surgically induced in tibiae of skeletally mature New Zealand white rabbits. Animals were allocated to one of four groups-(1) negative control (empty defect, healing for 8 weeks), (2 and 3) acute treatment with AIBG (healing for 4 or 8 weeks), and (4) chronic treatment with AIBG (injection 4 weeks post defect creation and then healing for 8 weeks). Bone formation was analyzed qualitatively and semi-quantitatively through histology. Samples were imaged using dual-energy X-ray absorptiometry and computed tomography for defect visualization and volumetric reconstruction, respectively. Delayed healing or non-healing was observed in the negative control group, whereas defects treated with AIBG in an acute setting yielded bone formation as early as 4 weeks with bone growth appearing discontinuous. At 8 weeks (acute setting), substantial remodeling was observed with higher degrees of bone organization characterized by appositional bone growth. The chronic healing, experimental, group yielded bone formation and remodeling, with no indication of non-union after treatment with AIBG. Furthermore, bone growth in the chronic healing group was accompanied by an increased presence of osteons, osteonal canals, and interstitial lamellae. Qualitatively and semiquantitatively, chronic application of AI facilitated complete bridging of the induced non-union defects, while untreated defects or defects treated acutely with AIBG demonstrated a lack of complete bridging at 8 weeks.