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Lixin Xie,1,* Lihua Feng,1,* Xiaomin Tang,1 Yunping Xu,1 Hengyi Xu,2 Yang Liu1 1Department of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hengyi Xu, State Key Laboratory of Food Science and Resources, Nanchang University, 235 Nanjing East Road, Nanchang, 330047, People’s Republic of China, Tel +0086-791-8830-4447-ext-9520, Fax +0086-791-8830-4400, Email kidyxu@163.com; HengyiXu@ncu.edu.cn Yang Liu, Department of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 minde Road, Nanchang, 330006, People’s Republic of China, Tel +86-791-8631-1209, Email ocean3166@yeah.netPurpose: To evaluate the therapeutic effect of oral administration of Lactiplantibacillus plantarum P101 (P101) on skeletal injury in young rats exposed to titanium dioxide nanoparticles (TiO2 NPs), and explore the potential mechanism.Methods: Four-week-old male rats were orally administration to TiO2 NPs and supplemented with P101 2 hours later for 4 weeks. The growth and development, food intake, bone metabolism and serum inflammatory markers of the rats were evaluated. Their tibias were observed and evaluated using microcomputed tomography (micro-CT), tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry (IHC) and real-time quantitative PCR (RT-qPCR). We observed the tibia growth plate using safranin and fast green staining. 16S rDNA sequence analysis of fecal samples was performed to observe changes in the gut microbiota.Results: Our results showed that TiO2 NPs can lead to bone growth inhibition and osteoporosis, induce intestinal flora imbalance, and induce inflammation in young rats. Further mechanistic studies suggested that TiO2 NPs disrupts intestinal flora and increases serum IL-1β levels, which increased the expression of RANKL in bone, thereby enhancing osteoclast differentiation and function, leading to bone loss. Through a P101 supplementation experiment, we found that P101 ameliorated the inflammation and osteoporosis on bone caused by TiO2 NPs.Conclusion: This study showed that the mechanism by which P101 alleviates bone damage caused by TiO2 NPs may be through restoring intestinal microbial homeostasis and inhibiting inflammatory response. Keywords: TiO2 NPs, P101, young rats, intestinal flora, bone injury, IL-1&#x03B2

BACKGROUND: Platelet-rich fibrin (PRF) has many advantages, such as simple preparation, low production cost, and high safety, and has been widely used in the study of bone defect repair in oral and maxillofacial surgery, but there are problems such as too fast degradation rate and short release time of growth factors. OBJECTIVE: PRF was loaded into gelatin methacryloyl (GelMA) hydrogel and its osteogenic properties were analyzed by in vivo and in vitro experiments. METHODS: (1) New Zealand white rabbit venous blood was extracted to prepare PRF. GelMA hydrogels containing 0, 0.05, 0.075, and 0.1 g PRF were prepared, respectively, and were recorded as GelMA, GelMA/PRF-0.05, GelMA/PRF-0.075, and GelMA/PRF-0.1, respectively, to characterize the micromorphology and in vitro slow-release properties of the hydrogels. (2) Four kinds of hydrogels were co-cultured with MC3T3-E1 cells, respectively, and the cell proliferation activity was detected with the single cultured cells as the control. After osteogenic induction, alkaline phosphatase activity, mineralization ability, mRNA and protein expression levels of osteogenic genes (osteocalcin, osteopontin, RUNX2), ERK1/2-p38 MAPK pathway protein mRNA and protein expression levels were detected. (3) Fifteen New Zealand white rabbits were taken. Four full-layer bone defects of 8 mm diameter were prepared in the skull of each rabbit, one of which was implanted without any material (blank control group), and the other three were implanted with GelMA hydrogel, PRF, and GelMA/PRF-0.1 hydrogel, respectively. The bone defect was detected by Micro-CT and bone morphology was observed at 4, 8, and 12 weeks after operation. RESULTS AND CONCLUSION: (1) Scanning electron microscopy observed that all the hydrogels of the four groups had honeycomb pore structure, and the pore size of the hydrogels decreased slightly with the increase of PRF content, but there was no significant difference between the groups. The three groups of GelMA/PRF hydrogel could release transforming growth factor β1 and insulin-like growth factor 1 at a certain rate, and the cumulative release of transforming growth factor β1 and insulin-like growth factor 1 increased significantly with the extension of time. (2) CCK-8 assay and live/dead staining showed that GelMA/ PRF hydrogel could promote the proliferation of MC3T3-E1 cells. The results of alkaline phosphatase staining, alizarin red staining, and osteogenic gene detection showed that GelMA/PRF hydrogel could promote the osteogenic differentiation of MC3T3-E1 cells, and inhibit the expression of ERK1/2-p38 MAPK pathway protein, and showed a PRF content dependence. (3) Micro-CT scan showed that the bone mineral density and bone volume fraction in the bone defect of GelMA/PRF-0.1 hydrogel group were higher than those in the other three groups (P < 0.05). Hematoxylin-eosin staining showed that compared with the other three groups, GelMA/PRF-0.1 hydrogel group had faster and more mature new bone formation at the bone defect. (4) These findings indicate that GelMA/PRF hydrogel has good osteogenic activity both in vivo and in vitro, which may be related to inhibiting the expression of ERK1/2-p38 MAPK pathway protein. [ABSTRACT FROM AUTHOR]

There are conflicting reports both within the lay media and scientific literature regarding the use and benefit of dietary practices that aim to reduce CHO intake in endurance athletes. This study aimed to determine the prevalence of intentional reduction of CHO intake and fasted training in elite endurance‐based athletes using a semi‐quantitative questionnaire. Bone is a nutritionally modulated tissue; therefore, this study also aimed to explore if these dietary practices are potentially associated with bone injury incidence. The reported reduction of CHO intake was prevalent (28%) with the primary motivation being maintenance or manipulation of body composition. However, discrepancies in athletes' awareness of CHO intake were identified providing a potential avenue of intervention especially within applied practice. The use of fasted training was more prevalent (38%) with athletes using this practice for both body composition manipulation and promoting a desired adaptive response. Forty‐four per cent of participants had suffered a radiographically confirmed bone injury at some point in their career. There was no association between reduction in CHO intake and bone injury incidence; however, the incidence of bone injury was 1.61 times higher in those who currently use fasted training compared to those who have never used it or who have used it in the past. Although a direct causal link between these dietary practices and the incidence of bone injury cannot be drawn, it provides robust justification for future investigations of the potential mechanisms that could explain this finding. Highlights: The self‐reported use of reductions in CHO intake (28%) and fasted training (38%) is prevalent in elite endurance‐based athletes and comparable to previous investigations in this area. Controlling body composition and promoting adaptive responses were common rationales for use.The incidence of bone injury is also high (44%) and there may be some association between bone injury incidence and fasted training. Further controlled experimental studies are required to determine the direct effect of nutritional strategies commonly adopted by endurance athletes on bone metabolism both acutely and chronically.There appears to be a gap in some athlete's knowledge and awareness of CHO rich foods and appropriate consumption of CHO to support endurance training and performance according to current guidelines. Future work should aim to explore and address this area further. [ABSTRACT FROM AUTHOR]

Preoperative radiotherapy (RT) for non-metastatic rectal cancer reduces local recurrence rates but can cause pelvic insufficiency fractures. Despite the high morbidity from RT-induced skeletal injuries, predictive and preventive measures are lacking. How these injuries are reflected by bone biomarkers are largely unknown. The aim was to assess longitudinal changes in bone biomarkers and their relation to RT-related bone injuries in women with rectal cancer. This longitudinal cohort study includes 47 women with non-metastatic rectal cancer treated with surgery ± preoperative RT with or without chemotherapy. Sclerostin, bioactive sclerostin, C-terminal telopeptide cross-links of collagen type I (CTX), bone-specific alkaline phosphatase (BALP), and type I procollagen intact N-terminal propeptide (PINP) were measured at baseline, after RT, and 1 yr postoperatively. Pelvic magnetic resonance imaging was used for detection of skeletal injury. Sixteen of 36 (44%) irradiated women had radiation-induced bone injuries and were compared to 11 women (RT–) and 20 women (RT+) without bone injuries. Serum CTX, BALP, and PINP increased during the first year after RT in women with radiation-induced bone injuries. The difference in mean change of CTX (p=.037) and BALP (p=.042) was conferred by longitudinal regression analyses adjusted for serum estradiol. Serum sclerostin and bioactive sclerostin remained stable over time. Taken together, bone markers may be of interest for future research on fracture prediction or preventive measures in women susceptible to radiation-induced bone injury. Due to few measure points, the full pattern cannot be captured regarding the relation over time between bone biomarkers and skeletal injury from irradiation. Lay Summary: Radiation therapy (RT) for rectal cancer before surgery reduces the risk of cancer recurrence, but can cause injuries to the pelvic bone. Despite the high morbidity from RT-caused skeletal injuries, predictive and preventive measures are lacking. How these bone injuries are reflected by bone biomarkers measured in serum is largely unknown. The aim of this study was to measure serum bone biomarkers and their relation to RT-related bone injuries in women with rectal cancer. The study group included 47 women with rectal cancer treated with surgery ± preoperative RT. Pelvic magnetic resonance imaging was used for detection of skeletal injury. The bone biomarkers sclerostin, bioactive sclerostin, C-terminal telopeptide cross-links of collagen type I (CTX), bone-specific alkaline phosphatase (BALP), and type I procollagen intact N-terminal propeptide (PINP) were measured at baseline, after RT, and 1 yr after surgery. Sixteen of 36 (44%) irradiated women had radiation-caused bone injuries and were compared to 31 women without bone injuries. Serum CTX, BALP, and PINP increased during the first year after RT in women with radiation-caused bone injuries. In summary, bone markers may be of interest for future research on fracture prediction or preventive measures in women prone to radiation-caused bone injury. [ABSTRACT FROM AUTHOR]

Complex bone injuries in the hand and forearm pose considerable physical and psychological challenges to patients. However, there is limited research on the psychological effects of these injuries. This study seeks to clarify the psychological impact and frequency of injuries in various hand bones. This cross-sectional study included 166 patients with complex hand and forearm injuries. Injuries were classified based on amputations and fractures involving phalanges, fingers, and other bones. Psychological assessments utilised standardised tools to gauge post-traumatic stress disorder (PTSD) levels. Our findings suggest that injury rates differ among the phalanges and individual fingers. The intermediate phalanx (P2) of the thumb had the most injuries, while no injuries were found in the proximal phalanx (P1) of the small finger. Amputations and fractures were found to be positively associated with increased symptoms of PTSD. This study emphasises the importance of recognising the psychological effects of hand and forearm bone injuries. The data indicate the need for a multi-disciplinary treatment approach that includes psychological interventions for optimal patient care. The study emphasises the necessity for additional research to further investigate these matters. [ABSTRACT FROM AUTHOR]

Abstract Articular cartilage damage is often caused by joint disease, trauma, and aging in everyday life. Cartilage damage usually refers to some changes in the normal structure and a gradual loss of function. Local discomforts, such as slight swelling or pain, may occur. Due to the lack of blood vessels and nerves in articular cartilage, articular cartilage damage is difficult to repair, making the detection and repair of articular cartilage damage difficult. New detection and repair technologies are urgently needed. The existing treatment methods are often used to monitor the internal environment and repair cartilage by implanting stents. Due to its high precision and simulation, 3D printing has shown great potential in carrier drug refinement and detection sensing and has become one of the more ideal technologies in the biomedical field. This article reviews the mitigation measures of bone injury, 3D printing technology, and treatment strategies for bone injury based on 3D printing technology. In addition, some challenges and possible solutions are also put forward for the treatment of bone injuries, as well as some possible development directions in the future.

BACKGROUND: Human amniotic epithelial cells, as a new type of seed cells, play an important role in bone injury repair. OBJECTIVE: To investigate the potential regulatory mechanism of osteogenic differentiation of human amniotic epithelial cells in coculture with osteoblasts. METHODS: Human amniotic epithelial cells were extracted by the enzyme digestion method. The proliferation of primary cells was described by the real-time cell analysis system xCELLigence RTCA S16. Human amniotic epithelial cells were co-cultured with osteoblasts by Transwell and corresponding samples were treated with siRNA-YAP1. The osteogenic differentiation of human amniotic epithelial cells was evaluated by detecting osteogenic associated proteins. RESULTS AND CONCLUSION: (1) Primary human amniotic epithelial cells were adherent within 12 hours and entered an exponential growth period from 24 to 48 hours. (2) During coculture, human amniotic epithelial cells showed a trend of osteogenic differentiation, and the expression of YAP1 protein was increased in Hippo signaling pathway. (3) After siRNA-YAP1 was added during coculture, the expression of YAP1 protein in the Hippo signaling pathway was decreased and the osteogenic differentiation ability of human amniotic epithelial cells was weakened. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have found that naringin affects bone metabolism directly through Wnt, transforming growth factor β, MAPK signaling pathway, and osteoclast signaling pathway, as well as indirectly through P13K-Akt and vascular endothelial growth factor signaling pathway. Naringin can promote bone repair and retard osteoporosis. OBJECTIVE: To investigate the effect of naringin on the proliferation and osteogenic differentiation of osteoblasts by targeting the activation of connexin 43/ERK1 signaling pathway through down-regulation of miR-206. METHODS: Rat osteoblasts (ROB cells) were treated and cultured with different concentrations of naringin (1, 10, 100 mg/L and 1, 10 g/L), and the cell proliferation was detected by cell counting kit-8 assay. Naringin at 100 mg/L and 1, 10 g/L were used for subsequent experiments. Osteoblasts with nondrug culture were used as controls. RT-qPCR was used to detect the relative expression levels of miR-206, connexin 43 and ERK1 mRNAs in ROB cells to verify their targeting relationship. Western blot was used to detect the protein expression levels of ERK1/2 and P-ERK in ROB cells. Alkaline phosphatase activity and calcification ability in ROB cells were observed by alkaline phosphatase staining and alizarin red staining, respectively. RESULTS AND CONCLUSION: Naringin significantly promoted the proliferation activity of ROB cells (P < 0.05). The absorbance value and relative proliferation rate of ROB cells increased as the administration concentration of naringin increased in a certain range. When the mass concentration was 1 g/L, the cell proliferation activity was the strongest. Naringin significantly inhibited the expression of miR-206 mRNA in ROB cells and promoted the expression of connexin 43 mRNA and ERK1/2 and P-ERK protein (P < 0.05). Naringin could significantly promote the activity and expression of alkaline phosphatase and the level of cellular calcification in ROB cells (P < 0.05). Moreover, naringin at 1 g/L showed the best effect. To conclude, naringin can target and activate the connexin 43/ERK1 signaling pathway by down-regulating the expression of miR-206, thereby promoting the proliferation and osteogenic differentiation of ROB cells. [ABSTRACT FROM AUTHOR]

The investigation of bone injuries is an essential topic in forensics. We sometimes have to deal with charred or dismembered human remains that have lost soft tissue, making it difficult to diagnose the mechanisms of injury that led to death. Our contribution aims to share with the scientific community how we approached two cases of very different bone injuries and the techniques used to differentiate relevant pathology findings of bone fragments. Two cases are analyzed from the case history of the forensic medicine institute of Palermo. PMCT made it possible to differentiate heat bone lesions from traumatic lesions. The stereomicroscope was superior to PMCT in being able to better characterize and evaluate shear injuries, allowing a more accurate measurement of acute lesions. Injury to bone remains can be appropriately investigated with rapid techniques such as PMCT and stereomicroscopy. The presented methodology shows the importance of a multidisciplinary approach when dealing with bone injuries in forensics that could find further applications in other circumstances to answer forensic questions. [ABSTRACT FROM AUTHOR]

Background: Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor that is commonly used to treat high blood pressure and heart failure. While it is generally well-tolerated, some studies have suggested that it may affect bone healing, suggesting that lisinopril treatment was associated with an increase in the CD34 bone healing marker in patients with tibial fractures. CD34 is a protein that is involved in the formation of new blood vessels and has been shown to play a role in bone healing. Methods: The study used 24 rabbits with artificially induced tibial bone fracture divided into 4 groups (6 rabbits each), the control group treated with distilled water and 3 groups treated with lisinopril. Each group were sacrificed for immunohistochemical study on 3 timepoints at day 7, 14, and 21. Results: Indicated that the lisinopril group had significantly higher levels of CD34 than the control group. Conclusion: While the results of this study suggest that lisinopril may have a positive effect on bone healing, more research is needed to confirm these findings and to determine the mechanisms by which lisinopril may affect bone healing. It is also important to note that lisinopril may have other potential side effects, and patients should discuss any concerns with their healthcare provider. [ABSTRACT FROM AUTHOR]

Background. Adipose-derived stem cells (ADSCs) are a promising source for the regeneration of bone tissue injuries. At the same time, three-dimensional cultures provide spatial organization of stem cells for optimal intercellular signaling, contact interaction and increase the efficiency of directed osteogenic differentiation prior to further transplantation. The aim of the study was to establish the regenerative potential of mouse adipose-derived stem cells in micromass grafts differentiated into the osteogenic direction to restore the bone injury in mice. Methods. Three-dimensional micromass cultures of murine ADSCs with further differentiation into osteogenic direction were obtained. The migration potential of cells from micromass in vitro and the effectiveness of differentiation by staining for alkaline phosphatase were evaluated. Mice with the model of femoral bone injury were transplanted with ADSCs micromass grafts and 21 days later the lesion site was examined by histological and morphometric methods. Results. The protocols for the cultivation and directed osteogenic differentiation of ADSCs in the three-dimensional micromass culture have been developed. Alkaline phosphatase production was demonstrated in cells that migrated from micromass, confirming the effectiveness of differentiation. In macroscopic examination 21 days after graft transplantation, the defect sites in femur were filled with dense tissue, while in control bones without the use of transplants, the size of the defect by 80 ± 6 % corresponded to the initial diameter and depth of injury. Histological examination of femoral bone lesions in the area of transplantation of micromass grafts revealed the formation of granulation tissue followed by the replacement of defects with newly formed bone tissue with thickening of periosteum and compact bone substance, similar to callus in fracture regeneration. In animals that underwent transplantation of micromass without prior osteogenic differentiation, the diameter of the zone of active regeneration of the diaphysis at the site of injury was 1.3 ± 0.2 mm while in the group with transplantation of directed differentiated graft it was significantly lower (0.37 ± 0.12 mm, p ≤ 0.05). Conclusions. Three-dimensional grafts of adipose-derived multipotent mesenchymal stromal cells cultured in micromass are able to improve bone tissue regeneration in a model of bone injury in mice. In this case, the grafts differentiated into osteogenic direction, provide better morphological indicators of bone recovery, compared with the micromass without prior differentiation.

Purpose: To evaluate the therapeutic effect of oral administration of Lactiplantibacillus plantarum P101 (P101) on skeletal injury in young rats exposed to titanium dioxide nanoparticles (TiO 2 NPs), and explore the potential mechanism., Methods: Four-week-old male rats were orally administration to TiO 2 NPs and supplemented with P101 2 hours later for 4 weeks. The growth and development, food intake, bone metabolism and serum inflammatory markers of the rats were evaluated. Their tibias were observed and evaluated using microcomputed tomography (micro-CT), tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry (IHC) and real-time quantitative PCR (RT-qPCR). We observed the tibia growth plate using safranin and fast green staining. 16S rDNA sequence analysis of fecal samples was performed to observe changes in the gut microbiota., Results: Our results showed that TiO 2 NPs can lead to bone growth inhibition and osteoporosis, induce intestinal flora imbalance, and induce inflammation in young rats. Further mechanistic studies suggested that TiO 2 NPs disrupts intestinal flora and increases serum IL-1β levels, which increased the expression of RANKL in bone, thereby enhancing osteoclast differentiation and function, leading to bone loss. Through a P101 supplementation experiment, we found that P101 ameliorated the inflammation and osteoporosis on bone caused by TiO 2 NPs., Conclusion: This study showed that the mechanism by which P101 alleviates bone damage caused by TiO 2 NPs may be through restoring intestinal microbial homeostasis and inhibiting inflammatory response., Competing Interests: Lixin Xie and Lihua Feng are co-first authors for this study. The authors report no conflicts of interest in this work., (© 2024 Xie et al.)

Copyright of Chinese Medical Equipment Journal is the property of Chinese Medical Equipment Journal Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Beyond the sensation of pain, peripheral nerves have been shown to play crucial roles in tissue regeneration and repair. As a highly innervated organ, bone can recover from injury without scar formation, making it an interesting model in which to study the role of nerves in tissue regeneration. As a comparison, tendon is a musculoskeletal tissue that is hypo-innervated, with repair often resulting in scar formation. Here, we reviewed the significance of innervation in 3 stages of injury repair (inflammatory, reparative, and remodeling) in 2 commonly injured musculoskeletal tissues: bone and tendon. Based on this focused review, we conclude that peripheral innervation is essential for phases of proper bone and tendon repair, and that nerves may dynamically regulate the repair process through interactions with the injury microenvironment via a variety of neuropeptides or neurotransmitters. A deeper understanding of neuronal regulation of musculoskeletal repair, and the crosstalk between nerves and the musculoskeletal system, will enable the development of future therapies for tissue healing. Lay Summary: Accumulating evidence has shown that, across organs systems, peripheral nerves regulate the process of tissue repair and regeneration. This is particularly relevant in the context of musculoskeletal injuries such as those affecting the bone and tendon. The question then arises: what is the function of peripheral innervation in the repair of bone and tendon injuries? This review offers an in-depth look at the ways in which nerves regulate the healing of bone and tendon injuries at various stages of recovery. A deeper comprehension of the influence of nerves on the repair of these tissues could pave the way for the development of future therapeutic strategies for tissue healing. [ABSTRACT FROM AUTHOR]

Having vitamin D levels within normal limits is important for bone and muscle health and its deficiency may increase the risk of injury. The aim of this cross-sectional study was to investigate whether vitamin D levels are different in indoor and outdoor athletes and its levels increase the risk of injury. Serum vitamin D levels were measured in Caucasian adolescent athletes, who admitted to the sports medicine polyclinic due to a routine health check or injury. The study was carried out at 38°26′ north latitude in İzmir between June and September 2019. After the physical examination of the injured athletes, the diagnoses were made accompanied by the findings obtained by imaging methods in cases of necessity. A total of 256 athletes, including swimmers (n = 87), basketball players (n = 104), and football (n = 65) players aged 13.2 (± 2.2) years, were investigated. The average serum vitamin D (25(OH)D) level in athletes was 29.2 (±10.0) ng/mL (6.0–66.0 ng/mL). Forty-six of all athletes (18%) had vitamin D deficiency, with a mean value of 15.7 (±4.0) ng/mL, and 93 of them (36.3%) had vitamin D deficiency with a mean value of 25.2 (±2.4) ng/mL. While vitamin D levels were significantly higher in football players (32 ng/mL) than in other athletes (p < 0.05), it was similar in basketball players (27 ng/mL) and swimmers (26 ng/mL) (p > 0.05). Vitamin D levels (26 ng/mL) of the injured athletes were significantly lower than those of the non-injured athletes (30 ng/mL) (p = 0.001). Bone injuries were significantly related to Vitamin D levels (p < 0.001) but not with muscle injuries (p > 0.05). Frequency of vitamin D deficiency and insufficiency is higher in indoor athletes andis especially associated with risk of bone injuries. In order to examine the effect of vitamin D level on bone mineral density, comprehensive prospective studies are required. [ABSTRACT FROM AUTHOR]

Abstract Background Synthetic biomaterials assist in modulating the vascular response in an injured bone by serving as delivery vehicles of pro-angiogenic molecules to the site of injury or by serving as mimetic platforms which offer support to cell growth and proliferation. Methods This study applied natural phospholipid modified protein technologies together with low temperature three-dimensional printing technology to develop a new model of three-dimensional artificial bone scaffold for potential use in repairing body injuries. The focus was to create a porous structure (PS) scaffold of two components, Bone Morphogenetic Protein-2 and Human Beta Defensin-3 (BMP2 and hBD3), which can synchronously realize directional bone induction, angiogenesis and postoperative antibacterial effects. BMP2 induces osteogenesis, whereas hBD3 is antibacterial. Results Our data showed that in the BMP2-hBD3-PS or hBD3-PS scaffolds, BMP2 had a slow-release rate of about 40% in 30 days, ensuring that BMP2 could penetrate into stem cells for osteogenic differentiation for a long time. The scaffolds promoted cell growth when in combination with BMP2, thus showing its importance in promoting cell growth. Alkaline Phosphatase (ALP) staining showed that the ALP content of BMP2-hBD3-PS and BMP2-PS had a significant increase in samples that contained BMP2, thus showing that these scaffolds promoted osteogenic differentiation. In all the constructs that had hBD3, they displayed antibacterial properties with hBD3, having a slow release of about 35% in 30 days, thus ensuring they provided protection. Conclusion Based on this study, the 3D printed BMP2 scaffolds show a great potential for the development of biodegradable bone implants. Level of evidence Level II, experimental comparative design.

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The development and validation of a new experimental model that reflects the clinical characteristics of polymorbid pathology (including obesity, acute inflammation of the gastrointestinal tract, antibiotic-induced dysbiosis, and bone injury) with the general characteristics of systemic inflammatory response syndrome became the basis for testing of the efficiency of probiotics according to the age of experimental animals. The concentration of osteocalcin and matrix metalloproteinase-1 significantly increased in 7-month-old male Wistar stock rats under the influence of probiotics as compared to animals at the age of 9 months. A mixture of probiotic containing Lactobacillus acidophilus (LA-5) and Bifidobacterium animalis subsp. lactis (BB-12) strains at a concentration of 108 CFU per animal demonstrated its effectiveness in comparison with other used probiotics in relation to most of the studied parameters. Zinc-containing biomolecules (osteocalcin, bone fraction and total alkaline phosphatase, matrix metalloproteinase-1) are metabolic regulators modulated by probiotic strains. [ABSTRACT FROM AUTHOR]

We present a case of a 23-year-old male patient who presented with a blade knife completely wedged and penetrated on his humerus after a stab wound to his left upper extremity. On palpation, a foreign body was palpated under the skin on the deltoid area. The blade was stuck in the bone, so the surrounding bone tissue was osteotomised until the blade was released. The patient evolved favorably, and at three months follow up, he has a full functional recovery of his arm. Stab wounds are prevalent in emergency departments; however, stab wounds with bone involvement have rarely been reported in the literature. When encountering a blade stuck in bone tissue, removing the blade while avoiding orthopedic, neurological and vascular injuries should be the main goal of the treatment. To the best of our knowledge, this is the third reported case of an intraosseous foreign body in the humerus secondary to a stab wound.

For this study, we investigate more deeply the effect calcium (Ca) develops on the mechanism underlying fluoride-triggered osteocyte apoptosis. We detected the morphology of osteocytes by HE staining, mitochondrial microstructure by using the transmission electron microscope, and the biochemical indexes related to bone metabolism and the expression of apoptosis-related genes. These results showed that NaF brought out the reduced osteocytes and ruptured mitochondrial outer membrane, with a significantly increased StrACP activity by 10.414 IU/L at the 4th week (P < 0.05), markedly upregulating the mRNA expression of Bax, Cyto-C, Apaf-1, caspase-7, ROCK-1, BMP-2, and BGP (P < 0.01), as well as caspase-6 (P < 0.05), while downregulating Bcl-2 by 61.3% (P < 0.01). Through immunohistochemical analysis, we also found that NaF notably increased the protein expression of ROCK-1 (P < 0.05) and Cyto-C, BMP-2, and BGP (P < 0.01), suggesting that NaF triggered the activation of the mitochondrial apoptotic pathway and Rho/ROCK signaling pathway. Nevertheless, 1% Ca supplementation in diet notably enhanced the mRNA expression of Bcl-2 by 39.3% (P < 0.01), thus blocking the increment of the expression of mitochondrial apoptotic pathway–related genes and ROCK-1. Meanwhile, Ca could attenuate the StrACP activity by 10.741 IU/L at the 4th week (P < 0.05) and protect the integrity of the mitochondrial outer membrane. These findings strongly suggest that 1% Ca abated the mitochondrial apoptosis pathway by increasing the anti-apoptotic gene Bcl-2 expression, and effectively inhibited the hyper-activation of ROCK-1, dually protecting the structural integrity of the mitochondrial outer membrane and maintaining normal cellular metabolic function. [ABSTRACT FROM AUTHOR]

Background: Synthetic biomaterials assist in modulating the vascular response in an injured bone by serving as delivery vehicles of pro-angiogenic molecules to the site of injury or by serving as mimetic platforms which offer support to cell growth and proliferation. Methods: This study applied natural phospholipid modified protein technologies together with low temperature three-dimensional printing technology to develop a new model of three-dimensional artificial bone scaffold for potential use in repairing body injuries. The focus was to create a porous structure (PS) scaffold of two components, Bone Morphogenetic Protein-2 and Human Beta Defensin-3 (BMP2 and hBD3), which can synchronously realize directional bone induction, angiogenesis and postoperative antibacterial effects. BMP2 induces osteogenesis, whereas hBD3 is antibacterial. Results: Our data showed that in the BMP2-hBD3-PS or hBD3-PS scaffolds, BMP2 had a slow-release rate of about 40% in 30 days, ensuring that BMP2 could penetrate into stem cells for osteogenic differentiation for a long time. The scaffolds promoted cell growth when in combination with BMP2, thus showing its importance in promoting cell growth. Alkaline Phosphatase (ALP) staining showed that the ALP content of BMP2-hBD3-PS and BMP2-PS had a significant increase in samples that contained BMP2, thus showing that these scaffolds promoted osteogenic differentiation. In all the constructs that had hBD3, they displayed antibacterial properties with hBD3, having a slow release of about 35% in 30 days, thus ensuring they provided protection. Conclusion: Based on this study, the 3D printed BMP2 scaffolds show a great potential for the development of biodegradable bone implants. Level of evidence: Level II, experimental comparative design. [ABSTRACT FROM AUTHOR]

Abstract Background Bone fracture healing is dependent upon the rapid migration and engraftment of bone marrow (BM) progenitor and stem cells to the site of injury. Stromal cell-derived factor-1 plays a crucial role in recruiting BM cells expressing its receptor CXCR4. Recently, a CXCR4 antagonist, plerixafor, has been used to mobilize BM cells into the blood in efforts to enhance cell migration to sites of injury presumably improving healing. In this study, we employed zirconium-89 (89Zr)-oxine-labeled BM cells imaged with positron emission tomography (PET)/computed tomography (CT) to visualize and quantitate BM cell trafficking following acute bone injury and to investigate the effect of plerixafor on BM cell homing. Unilateral 1-mm incisions were created in the distal tibia of mice either on the same day (d0) or 24 h (d1) after 89Zr-oxine-labeled BM cell transfer (n = 4–6, 2–2.3 × 107 cells at 9.65–15.7 kBq/106 cells). Serial microPET/CT imaging was performed and migration of 89Zr-labeled cells to the bone injury was quantified. The effects of three daily doses of plerixafor on cell trafficking were evaluated beginning on the day of fracture generation (n = 4–6). The labeled cells localizing to the fracture were analyzed by flow cytometry and immunohistochemistry. Results In d0- and d1-fracture groups, 0.7% and 1.7% of administered BM cells accumulated within the fracture, respectively. Plerixafor treatment reduced BM cell migration to the fracture by approximately one-third (p

BACKGROUND: Increasing systematic reviews of acupuncture treatment for periarthritis of shoulder indicate that acupuncture treatment has better efficacy than western medicine. However, the methodological quality of these systematic reviews and the differences in efficacy between different acupuncture therapies are unclear. OBJECTIVE: To evaluate the methodological quality of systematic reviews regarding acupuncture therapy for periarthritis of shoulder and to compare the efficacy of different acupuncture therapies in treating periarthritis of the shoulder. METHODS: A total of seven electronic databases were searched for systematic reviews regarding different acupuncture therapies for periarthritis of the shoulder, from inception to December 28, 2019. The AMSTAR2 instrument was used to evaluate the methodological quality of included systematic reviews. The eligible randomized controlled trial (RCTs) were selected from the included systematic reviews and updated RCTs from the above systematic reviews to December 28, 2019. Cochrane risk of bias tool was used for the risk of bias of the included RCTs. Pairwise meta-analyses were performed using the random-effects model, and network meta-analysis of the included RCTs were performed the frequentist framework. All data analyses were completed in Stata 14.0. RESULTS AND CONCLUSION: Thirty-four qualified RCTs (n=3 098) were included from five critically low-quality systematic reviews and updated RCTs. Five interventions were ranked based on the ranking probability in the network meta-analysis. Compared with western medicine, warm acupuncture [odds ratio (OR)=1.26, 95% confidence interval (CI) (1.15, 1.39)] has the highest possibility to improve the symptoms of periarthritis of the shoulder, followed by thermo-sensitive moxibustion [OR=1.26, 95%CI (1.15, 1.39)], electroacupuncture [OR=1.21, 95%CI (1.10, 1.33)], filiform needle [OR=1.21, 95%CI (1.01, 1.24)]. In terms of visual analogue scale score, compared with western medicine, thermo-sensitive moxibustion [OR=0.12, 95%CI (0.03, 0.46)] had the highest possibility of reducing visual analogue scale score followed by warm acupuncture [OR=0.28, 95%CI (0.11, 0.75)] and electroacupuncture [OR=0.34, 95%CI (0.12, 0.96)]. Considering the pairwise meta-analyses and network meta-analysis of this study, among the four acupuncture therapies included, thermo-sensitive moxibustion and warm acupuncture can be considered as a complementary alternative to the treatment of periarthritis of the shoulder. However, given the critically low methodological quality of the included systematic reviews and poor reporting risk bias of RCTs, more rigorous design and standardized reporting are needed to further demonstrate the reliability of this study. [ABSTRACT FROM AUTHOR]

Osteotomy is a common step in oncological, reconstructive, and trauma surgery. Drilling and elevated temperature during osteotomy produce thermal osteonecrosis. Heat and associated mechanical damage during osteotomy can impair bone healing, with consequent failure of fracture fixation or dental implants. Several ex vivo studies on animal bone were recently focused on heating production during osteotomy with conventional drill and piezoelectric devices, particularly in endosseous dental implant sites. The current literature on bone drilling and osteotomic surface analysis is here reviewed and the dynamics of bone healing after osteotomy with traditional and piezoelectric devices are discussed. Moreover, the methodologies involved in the experimental osteotomy and clinical studies are compared, focusing on ex vivo and in vivo findings. [ABSTRACT FROM AUTHOR]

The musculoskeletal system has an integral role throughout life, including structural support to the body, protection, and allowing a range of fine to complex movements for daily living to elite sporting events. At various times, injuries to the musculoskeletal system occur resulting in varying levels of impact to the person both acutely and chronically. Specifically, there is a spectrum of complexity in orthopedic injuries, with some such as common muscle strains, that while burdensome will have no impact on life-long functional ability, and others that can result in long lasting disability. Focusing on extremity injuries, this review highlights: i)the current impact of orthopedic injuries in sport and daily life; ii) the foundation of bone and skeletal muscle repair and regeneration; and iii) the disruptions in regenerative healing due to traumatic orthopedic injuries. This review seeks to maximize the broad and collective research impact on sport and traumatic orthopedic injuries in search of promoting ongoing innovation for treatment and rehabilitation approaches aimed to improve musculoskeletal health throughout life. [ABSTRACT FROM AUTHOR]

Aim: Bone healing becomes problematic during certain states, such as trauma. This study verifies whether the application of c-myb with gelatin promotes bone healing during bone injuries. Materials & methods: A biodegradable membrane was modified with adenoviral vector c-myb (Ad/c-myb) and gelatin and applied in the bone injury site of rat tibia. Results:c-myb enhanced osteogenic differentiation and mineralization in bone marrow stromal cells after induction with osteogenic media. In vivo examination of rat tibia after application of the biodegradable membrane with Ad/c-myb and a gelatin layer demonstrated increased bone volume, bone mineral density, new bone formation and osteogenic molecules, compared with Ad/LacZ. Conclusion:c-myb has the potential to assist bone healing and may be applicable to the treatment of bone during injury. [ABSTRACT FROM AUTHOR]

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During the life time of the human, modelling and remodeling of the bone maintain a precise and dynamic balance. The material exchange in the bone is coordinated through the cells. Researches have found that bone regeneration is not only through the coordination of the cells, but also through the close connection between exosomes that carry and transfer proteins, lipids, and RNAs, and other tissues. Studies have shown that exosomes from various cell sources are involved in the exchange of intercellular substances and information around bone, which can promote the repair and regeneration various bone cells, and regulate the physical and pathological status of the bone. In this paper, the relationship between exosomes and bone regeneration is briefly described according to the recent research reports of exosomes in bone regeneration. [ABSTRACT FROM AUTHOR]

Objective(s):To study the effect of low-frequency vibration on bone marrow stromal cell differentiation and potential bone repair in vivo. Materials and Methods:Forty New Zealand rabbits were randomly divided into five groups with eight rabbits in each group. For each group, bone defects were generated in the left humerus of four rabbits, and in the right humerus of the other four rabbits. To test differentiation, bones were isolated and demineralized, supplemented with bone marrow stromal cells, and implanted into humerus bone defects. Varying frequencies of vibration (0, 12.5, 25, 50, and 100 Hz) were applied to each group for 30 min each day for four weeks. When the bone defects integrated, they were then removed for histological examination. mRNA transcript levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor k-B ligan, and pre-collagen type 1 a were measured. Results:Humeri implanted with bone marrow stromal cells displayed elevated callus levels and wider, more prevalent, and denser trabeculae following treatment at 25 and 50 Hz. The mRNA levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor k-B ligand, and pre-collagen type 1 a were also markedly higher following 25 and 50 Hz treatment. Conclusion:Low frequency (25–50 Hz) vibration in vivo can promote bone marrow stromal cell differentiation and repair bone injury.

For this study all autopsy reports of non-natural deaths performed at the Institute of Legal Medicine at the University of Cologne from a 10-year period (2008-2017) were examined in regards to the manner of non-natural death and their frequency and distribution of bone injuries (BI). 2026 cases (220 homicides, 421 suicides, 760 accidents, 393 possible suicides, 232 possible accidents) were reviewed. The highest frequency of BI was registered within homicides with 89.1%, second being accidents (79.3%), while suicides and poss. suicides were at 53.4% and 43.3%. Gunshots/explosions split between 52% for suicides and 33.6% for homicides, sharp force was to 56% found within homicides and with 29.8% in suicides. 63.7% of all blunt force was found in the accident category. The highest participation of BI and injuries across all body regions was found with gunshot homicides (100% BI, over every region). Intoxication showed the lowest BI over all with only 19.9% of all cases. Albeit several distinctive patterns were found, e.g. distinction between gunshots in suicides and homicides or high amount of BI in decayed corpses in homicides, a close examination on case by case basis, utilizing the forensic toolkit to its fullest, should always be attempted when examining decomposed or skeletal remains. [ABSTRACT FROM AUTHOR]

Osteotomy is a common step in oncological, reconstructive, and trauma surgery. Drilling and elevated temperature during osteotomy produce thermal osteonecrosis. Heat and associated mechanical damage during osteotomy can impair bone healing, with consequent failure of fracture fixation or dental implants. Several ex vivo studies on animal bone were recently focused on heating production during osteotomy with conventional drill and piezoelectric devices, particularly in endosseous dental implant sites. The current literature on bone drilling and osteotomic surface analysis is here reviewed and the dynamics of bone healing after osteotomy with traditional and piezoelectric devices are discussed. Moreover, the methodologies involved in the experimental osteotomy and clinical studies are compared, focusing on ex vivo and in vivo findings.

Dietary calcium (Ca) supplementation has beneficial effects on bone health. However, it is not clear whether a high calcium diet (HCD) following 5/6 nephrectomy (5/6 Nx) is beneficial to bone health. The aim of the present study was to examine the effects of an HCD on bone metabolism using a chronic kidney disease (CKD) mouse model. Male C57BL/6J mice were divided into three groups: Sham group, 5/6 Nx group and 5/6 Nx + HCD group. Mice were sacrificed 12 weeks post‑surgery. Calcium (Ca) and creatinine (Cr) were measured using standard colorimetric methods and picric acid methods, respectively. Bone metabolism‑associated markers, FGF‑23, PTH, ALP‑b and TRAP‑5b were measured using ELISA kits. Lumbar vertebrae histomorphological analysis was performed using hematoxylin and eosin staining. The expression of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) mRNA was detected using reverse transcription‑quantitative polymerase chain reaction. Impaired renal function and histopathological damage was indicated in 5/6 Nx mice. However, HCD had no significant effects on these changes in 5/6 Nx mice. Notably, mineral metabolism disorder and histopathological damage to lumbar vertebrae were markedly improved in HCD‑treated 5/6 Nx mice. Compared with 5/6 Nx mice, HCD supplementation significantly elevated the ratio of OPG/RANKL and inhibited RANKL mRNA expression in lumbar vertebrae. To conclude, the present findings indicated that increased Ca intake is effective in increasing bone mineral content of the lumbar vertebrae in 5/6 Nx mice. These results may provide a basis for the clinical use of dietary Ca supplementation as a therapeutic approach to treat CKD‑induced disturbance of mineral metabolism and bone loss. [ABSTRACT FROM AUTHOR]

Background: It is important to diagnose a scaphoid fracture accurately and start the correct treatment in the shortest time possible. However, the fracture of bone may not be visible on x-ray. In such cases, patients are clinically diagnosed with suspected or occult scaphoid fractures. The aim of this study was to define a scoring system based on physical examination to demonstrate the risk for bone injury in patients with clinically suspected and occult scaphoid fractures with negative radiographs and anatomical snuff box tenderness and to decrease the costs and workforce loss due to unnecessary treatment and magnetic resonance imaging (MRI). Materials and Methods: Patients were initially evaluated by the attendant orthopedic physician in the emergency service with X-ray of the wrist, and ten wrist physical examination techniques were used. The X-rays of patients were evaluated by three orthopedic surgeons. Finally sixty patients, who were diagnosed as having no fracture by all three orthopedic surgeon, were included in the study. The wrists of these patients were evaluated with MRI. Results: There were 46 male (77%) and 14 female (23%) patients with a mean age of 21.5 years (range 7-61 years). About 3.3% had triquetrum fracture, 15% had bone edema in the scaphoid and radius, 18.3% had distal radius fracture, 31.6% had scaphoid fracture, and 31.8% had no bone injury. A scoring system was also proposed. It can be predicted that in the physical examination of the wrist if the total score is higher than 6.5, the probability of fracture is 2.87 (positive likelihood ratio) fold compared to scores below 6.5. Conclusions: Proposal of this new scoring system was thought to be useful for predicting the risk for bone injury in patients with clinically suspected scaphoid fractures and making decision regarding therapeutic options. [ABSTRACT FROM AUTHOR]

Context: The female athlete triad (Triad) and relative energy deficiency in sport (RED-S) specify the consequences of energy imbalance. Athletic trainers (ATs) are positioned to identify athletes who are fueling themselves inadequately and experiencing related health and performance consequences. Objective: To assess the knowledge of collegiate ATs about the Triad and RED-S and to examine variability in related screening and referral behaviors among National Collegiate Athletic Association divisions. Design: Cross-sectional study. Setting: Collegiate athletic training departments. Patients or Other Participants: Head ATs at National Collegiate Athletic Association member institutions (n = 285, response rate = 33%). Main Outcome Measure(s): An electronic survey was administered. The number of Triad components that were correctly identified and screening and referral behaviors related to Triad components were measured. Results: Nearly all respondents (98.61% [n = 281]) had heard of the Triad; a smaller proportion (32.98% [n = 94]) had heard of RED-S. On average, respondents correctly identified 2 components of the Triad. We observed differences by sex, with women correctly identifying more components than men (U = 12.426, P = .003). More than half (59.93% [n = 163]) indicated that athletes at their institutions were screened for eating disorders. Nearly three-quarters (70.55% [n = 115]) of respondents indicated that all female athletes at their institutions were screened annually for menstrual dysfunction. More comprehensive referral behaviors for athletes identified as experiencing menstrual dysfunction or a bone injury (eg, athlete referred to a nutritionist, dietitian, or counselor) occurred at Division I institutions than at Division II and III institutions. Conclusions: Continuing education for ATs about the Triad and RED-S may encourage a more comprehensive approach to referral and screening after a diagnosis of menstrual dysfunction or bone-stress injury. Using institutional opportunities, such as preparticipation screening, for identifying components of the Triad or RED-S and specifying protocols for referring athletes who screen positive for 1 of these components should also be explored. [ABSTRACT FROM AUTHOR]