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Bone, a rigid yet regenerative tissue, has garnered extensive attention for its impressive healing abilities. Despite advancements in understanding bone repair and creating treatments for bone injuries, handling nonunions and large defects remains a major challenge in orthopedics. The rise of bone regenerative materials is transforming the approach to bone repair, offering innovative solutions for nonunions and significant defects, and thus reshaping orthopedic care. Evaluating these materials effectively is key to advancing bone tissue regeneration, especially in difficult healing scenarios, making it a critical research area. Traditional evaluation methods, including two-dimensional cell models and animal models, have limitations in predicting accurately. This has led to exploring alternative methods, like 3D cell models, which provide fresh perspectives for assessing bone materials' regenerative potential. This paper discusses various techniques for constructing 3D cell models, their pros and cons, and crucial factors to consider when using these models to evaluate bone regenerative materials. We also highlight the significance of 3D cell models in the in vitro assessments of these materials, discuss their current drawbacks and limitations, and suggest future research directions. This work addresses the challenge of evaluating bone regenerative materials (BRMs) crucial for bone tissue engineering. It explores the emerging role of 3D cell models as superior alternatives to traditional methods for assessing these materials. By dissecting the construction, key factors of evaluating, advantages, limitations, and practical considerations of 3D cell models, the paper elucidates their significance in overcoming current evaluation method shortcomings. It highlights how these models offer a more physiologically relevant and ethically preferable platform for the precise assessment of BRMs. This contribution is particularly significant for "Acta Biomaterialia" readership, as it not only synthesizes current knowledge but also propels the discourse forward in the search for advanced solutions in bone tissue engineering and regeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

Although previous studies have demonstrated the advantages of early surgery for traumatic spinal cord injury (SCI), the appropriate surgical timing for cervical SCIs (CSCIs) without bone injury remains controversial. Here, we investigated the influence of relatively early surgery within 48 h of injury on the neurological recovery of elderly patients with CSCI and no bone injury. In this retrospective multicenter study, we reviewed data from 159 consecutive patients aged ≥65 years with CSCI without bone injury who underwent surgery in participating centers between 2010 and 2020. Patients were followed up for at least 6 months following CSCI. We divided patients into relatively early (≤48 h after CSCI, n = 24) and late surgery (>48 h after CSCI, n = 135) groups, and baseline characteristics and neurological outcomes were compared between them. Multivariate analysis was performed to identify factors associated with neurological recovery. The relatively early surgery group demonstrated a lower prevalence of cardiac disease, poorer baseline American Spinal Injury Association (ASIA) impairment scale grade, and lower baseline ASIA motor score (AMS) than those of the late surgery group (P < 0.030, P < 0.001, and P < 0.001, respectively). Although the AMS was lower in the relatively early surgery group at 6 months following injury (P = 0.001), greater improvement in this score from baseline to 6-months post injury was observed (P = 0.010). Multiple linear regression analysis revealed that relatively early surgery did not affect postoperative improvement in AMS, rather, lower baseline AMS was associated with better AMS improvement (P < 0.001). Delirium (P = 0.006), pneumonia (P = 0.030), and diabetes mellitus (P = 0.039) negatively influenced postoperative improvement. Although further validation by future studies is required, relatively early surgery did not show a positive influence on neurological recovery after CSCI without bone injury in the elderly. [ABSTRACT FROM AUTHOR]

Critical bone defects resulting in delayed and non-union are a major concern in the field of orthopedics. Over the past decade, mesenchymal stem cells (MSCs) have become a promising frontier for bone repair and regeneration owing to their high expansion rate and osteogenic differentiation potential ex vivo. MSCs have also long been associated with their ability to modulate immune response in the recipients. These can even skew the immune response towards pro-inflammatory or anti-inflammatory type by sensing their local microenvironment. MSCs adopt anti-inflammatory phenotype at bone injury site and secrete various immunomodulatory factors such as IDO, NO, TGFβ1 and PGE-2 which have redundant role in osteoblast differentiation and bone formation. As such, several studies have also sought to decipher the immunomodulatory effects of osteogenically differentiated MSCs. The present review discusses the immunomodulatory status of MSCs during their osteogenic differentiation and summarizes few mechanisms that cause immunosuppression by osteogenically differentiated MSCs and its implication during bone healing. • Immunomodulation by MSCs plays critical role during bone regeneration. • Osteogenically differentiated MSCs retain immunomodulatory role. • Immune-regulation by MSCs during osteogenic differentiation can have clinical implications during bone repair. [ABSTRACT FROM AUTHOR]

Tibial stress injuries are challenging in terms of early diagnosis, management strategy, and safe return-to-play. In the present study, pain production associated with the application of therapeutic ultrasound (TUS) was used as a primary diagnostic tool to assess tibial bone stress injuries, and the sensitivity of this procedure was compared with Magnetic Resonance Imaging (MRI). The study was designed as a retrospective analysis of prospectively collected data on tibial bone stress injuries in elite Track and field athletes attending the National Track and Field Athletics Centre in Thessaloniki, Greece, in the period 1995–2007. All patients underwent evaluation by TUS, and the sensitivity of the procedure was compared with MRI. Four of 29 athletes showed a positive TUS examination for stress injury while MRI showed normal findings. Additionally, 5 athletes evidenced MRI findings typical of a tibial bone stress injury, while TUS evaluation was negative. Using MRI as the standard, TUS displayed a sensitivity of 79.2%. Therapeutic ultrasound is a reproducible modality with satisfactory reliability and sensitivity related to MRI, and could represent a useful tool for clinicians to primarily assess suspected tibial bone stress injuries in high qualification Track and Field athletes. • TUS is a cost-effective assessment tool for the diagnosis of bone stress injuries. • Tibial stress injuries were more frequent in running disciplines. • The current study does not intent to replace MRI for detection of bone stress injuries. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries remain a major medical problem worldwide and are associated with multiple causes, including gunshot wounds (GSWs), which are the second most common cause of brachial plexus injuries in peacetime and the main, or only, cause reported in wartime studies. The ulnar nerve (UN) is one of the most affected nerves. Peripheral nerve trauma may cause intense neuropathic pain, which is very difficult to control. Particularly UN gunshot injuries may impact individual daily life, as injuries to this nerve result in both sensory and motor deficits within the hand. We evaluated the improvement of neuropathic pain after surgical treatment in a consecutive series of 20 patients with UN injury due to GSWs. This single-center, retrospective, consecutive case series included 20 patients with UN injuries due to GSWs, who presented with excruciating neuropathic pain and underwent surgical treatment between 2005 and 2017. Of injuries, 13 occurred in the right upper limb (65%); 12 patients had a high UN injury (60%). Regarding associated injuries, 8 patients had bone injuries (40%), and 4 patients had arterial injuries (20%). A neuroma in continuity was detected in 8 cases (40%), and 4 patients (20%) had shrapnel lodged within the UN. All patients had severe neuropathic pain and functional deficit, with a mean visual analog scale score of 8.45 ± 1.4 and a mean reduction of 6.95 points 12 months after surgery; 10 patients (50%) had a British Medical Research Council score ≥M3. Surgery is an effective treatment for neuropathic pain from GSWs. Early isolated external neurolysis is associated with better pain management and functional outcomes postoperatively. [ABSTRACT FROM AUTHOR]

Biological functions and mechanical properties are vital factors for artificial bone materials, with great clinic demand for bone injuries and defects. This study highlights mechanical strengths, in vitro and i n vivo biological behaviors of the bioactive CaO–SiO 2 –P 2 O 5 glass - ceramics tailored by the nucleating agent P 2 O 5. A high mechanical flexural strength of ∼170 MPa and hardness of ∼720 HV were achieved, owing to strengthened Si–O bonds in the network. In vitro cell tests demonstrate remarkable viability (using L929 cells) and bioactivity (using bone marrow-derived mesenchymal stromal cells), associated with the release of Ca2+ ions in the solution due to weakened Ca–O bonds in the glass - ceramic network. The assay in the simulated body fluid revealed a formation of the hydroxyapatite-phase layer, which may act as a bridge to facilitate bioactivity on the CaO–SiO 2 –P 2 O 5 glass - ceramics. In vivo assay shows a significant bone-ingrowth capability on the CaO–SiO 2 –P 2 O 5 glass-ceramic. This work paves a promising route to utilize P 2 O 5 –nucleated CaO–SiO 2 –P 2 O 5 glass-ceramics for load-bearing bone replacement. [ABSTRACT FROM AUTHOR]

Pelvic radiotherapy (RT) increases the risk of pelvic insufficiency fractures. The aim was to investigate if RT is associated with changes in serum bone biomarkers in women with rectal cancer, and to examine the incidence of radiation-induced bone injuries and the association with bone biomarkers. Women diagnosed with rectal cancer stage I-III, planned for abdominal surgery ± preoperative (chemo) RT, were prospectively included and followed one year. Serum bone biomarkers comprised sclerostin (regulatory of bone formation), CTX (resorption), BALP and PINP (formation). A subgroup was investigated with annual pelvic magnetic resonance imaging (MRI). The association between RT and bone biomarkers was explored in regression models. Of 134 included women, 104 had surgery with preoperative RT. The formation markers BALP and PINP increased from baseline to one year in the RT-exposed group (p < 0.001, longitudinal comparison). In the adjusted regression analysis, the mean increase in PINP was higher in the RT-exposed than the unexposed group (17.6 (3.6–31.5) μg/L, p = 0.013). Sclerostin and CTX did not change within groups nor differed between groups. Radiation-induced injuries were detected in 16 (42%) of 38 women with available MRI. At one year, BALP was higher among women with than without bone injuries (p = 0.018, cross-sectional comparison). Preoperative RT was associated with an increase in the formation marker PINP, which could represent bone recovery following RT-induced injuries, commonly observed in participants evaluated with MRI. These findings should be further explored in larger prospective studies on bone health in rectal cancer patients. [ABSTRACT FROM AUTHOR]

Tmem119 was identified as a bone anabolic factor in osteoblasts, however the roles of Tmem119 on bone repair have remained unknown. Therefore, we herein investigated the roles of Tmem119 on bone repair by examining the bone repair process after a femoral bone defect using Tmem119-deficient mice. In Tmem119-deficient mice, bone repair after a femoral bone defect was significantly delayed 10 and 14 days after bone injury in female and male mice with 3-dimensional micro-computed tomography analyses, respectively. The number of alkaline phosphatase-positive cells at the damaged sites was significantly decreased 7 days after bone injury in Tmem119-deficient mice, although the number of Osterix-positive cells was not significantly different 4 days after bone injury. The number of tartrate-resistant acid phosphatase-positive multinucleated cells as well as the number and luminal area of CD31-positive vessels at the damaged sites were not significantly different between Tmem119-deficient and wild-type mice. The present study first showed that Tmem119 deficiency delayed bone repair partly through a decrease in the osteoblastic bone formation of differentiated osteoblasts. • Tmem119 deficiency delayed bone repair 10 and 14 days after a femoral bone defect in female and male mice. • Tmem119 deficiency decreased the number of ALP-positive cells at damaged site 7 days after bone defect in mice. • Tmem119 deficiency did not affect the number of Osterix-positive cells and osteoclasts or angiogenesis at damaged site. • The results suggest that Tmem119 contributes to bone repair partly through an increased number of osteoblasts in mice. [ABSTRACT FROM AUTHOR]

Silicon nitride is utilized clinically as a bioceramic for spinal fusion cages, owing to its high strength, osteoconductivity, and antibacterial effects. Nevertheless, silicon nitride exhibits suboptimal damping properties, a critical factor in mitigating traumatic bone injuries and fractures. In fact, there is a scarcity of spinal implants that simultaneously demonstrate proficient damping performance and support osteogenesis. In our study, we fabricated a novel sodium alginate-silicon nitride/poly(vinyl alcohol) (SA-SiN/PVA) composite scaffold, enabling enhanced energy absorption and rapid elastic recovery under quasi-static and impact loading scenarios. Furthermore, the study demonstrated that the incorporation of physical and chemical cross-linking significantly improved stiffness and recoverable energy dissipation. Concerning the interaction between cells and materials, our findings suggest that the addition of silicon nitride stimulated osteogenic differentiation while inhibiting Staphylococcus aureus growth. Collectively, the amalgamation of ceramics and tough hydrogels facilitates the development of advanced composites for spinal implants, manifesting superior damping, osteogenic potential, and antibacterial properties. This approach holds broader implications for applications in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Condylar stress fracture of the distal end of the third metacarpal/metatarsal (MC3/MT3) bones is a major cause of Thoroughbred racehorse injury and euthanasia worldwide. Functional adaptation to exercise and fatigue damage lead to structural changes in the subchondral bone that include increased modeling (resulting in sclerotic bone tissue) and targeted remodeling repair (resulting in focal resorption spaces in the parasagittal groove). Whether these focal structural changes, as detectable by standing computed tomography (sCT), lead to elevated strain at the common site of condylar stress fracture has not been demonstrated. Therefore, the goal of the present study was to compare full-field three-dimensional (3D) strain on the distopalmar aspect of MC3 bone specimens with and without focal subchondral bone injury (SBI). Thirteen forelimb specimens were collected from racing Thoroughbreds for mechanical testing ex vivo and underwent sCT. Subsequently, full-field displacement and strain at the joint surface were determined using stereo digital image correlation. Strain concentration was observed in the parasagittal groove (PSG) of the loaded condyles, and those with SBI in the PSG showed higher strain rates in this region than control bones. PSG strain rate in condyles with PSG SBI was more sensitive to CT density distribution in comparison with condyles with no sCT-detectable injury. Findings from this study help to interpret structural changes in the subchondral bone due to fatigue damage and to assess risk of incipient stress fracture in a patient-specific manner. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Recently, the prevalence of elderly patients suffering from cervical spinal cord injury (CSCI) without bone injury has been increasing in various countries. Pre-existing factors causing spinal cord compression, such as ossification of the posterior longitudinal ligament (OPLL), can increase the risk of CSCI without bone injury. However, no study has compared the prevalence of pre-existing factors between CSCI with and without bone injury. This study aimed to compare the prevalence of pre-existing factors between CSCI with and without bone injury.Methods: In 168 consecutive patients with CSCI, pre-existing factors including OPLL, posterior spur of the vertebral body, developmental stenosis, disc bulge and calcification of yellow ligament (CYL) were evaluated on imaging studies. The prevalence of each type of pre-existing factors was compared between patients with and without bone injury.Results: The prevalence of pre-existing factors in patients without bone injury (86%) was significantly higher than in those with bone injury (20%) (P < 0.001; odds ratio, 23.9). The most common pre-existing factor was OPLL followed by developmental stenosis, posterior spur, disc bulge and CYL in both groups. OPLL, development stenosis and posterior spur were significantly more common in patients without bone injury compared to those with bone injury (P < 0.01).Conclusions: Prevalence of pre-existing factors, such as OPLL, development stenosis and posterior spur was significantly higher in patients without bone injury than in those with bone injury. Thus, these pre-existing factors might be a potential risk of CSCI without bone injury. [ABSTRACT FROM AUTHOR]

• The utilization of mussel-inspired hydrogel can greatly enhance the efficacy of stem cells in bone/cartilage regeneration. • Mussel-inspired hydrogels presents a remarkable functional advantage in the context of bone/cartilage regeneration. • The application of mussel-inspired chemistry demonstrates practical feasibility in the modification of hydrogels. • The value of mussel-inspired hydrogels in various fields is gradually emerging, necessitating a comprehensive exploration. The clinical injury of bone and cartilage tissue is complex and specific, posing a significant threat to human health as traditional regenerative therapies (including autograft and allograft etc.) often result in side effects and poor prognosis. In this regard, hydrogel materials with unique three-dimensional structure, high water content, and biomimetic characteristics have emerged as promising candidates for supporting stem cells in achieving clinical bone/cartilage regeneration. However, the limited functionality of conventional hydrogels due to their single composition necessitates modification or enhancement for gaining specific properties. Mussel-inspired chemistry offers strong modification potential to hydrogels while improving various biological performances, making them widely applicable in bone/cartilage regeneration. In this review, we firstly provide a brief overview of common methods for designing hydrogels that promote bone/cartilage regeneration. Subsequently, typical functionalization approaches employed in mussel-inspired hydrogels including enhancing adhesion ability, improving antioxidant activity, augmenting loading capability along with the corresponding methodologies used to achieve these functionalizations were summarized. Finally, the challenges faced by mussel-inspired hydrogels were highlighted and potential directions for future research endeavors were proposed, aiming at providing novel ideas and inspiration to researchers. [ABSTRACT FROM AUTHOR]

Efficient bone reconstruction after bone injury remains a great challenge. Injectable supramolecular hydrogels based on amphiphilic peptide have been widely used due to their good biocompatability, non-immunogenicity, and manipulable physicochemical properties by sequence design. Herein, we used a well-studied hydrogelator, NapFFY, to coassemble with osteogenic growth peptide (OGP) to prepare a supramolecular hydrogel, NapFFY-OGP. Both in vitro and in vivo studies demonstrate that OGP was ideally synchronously, and continuously released from the hydrogel to effectively promote the regeneration and reconstruction of skull bone defects. More specifically, after the embedding the rat skull defect area with NapFFY-OGP hydrogels, a bone regeneration rate of 37.54% bone volume fraction (BV/TV) was achieved compared to that of NapFFY hydrogel group (25.09%). NapFFY-OGP hydrogel shows great promise in the clinic repair of bone defects in the future. [ABSTRACT FROM AUTHOR]

Background: Ankle fractures are the most common traumatic bone injuries of the lower limb. Over 50% of ankle fractures occur at the syndesmosis level (type AO B). The goal of treatment is to achieve an anatomical reduction and appropriate stabilization. The present study aimed to evaluate the clinical-functional and radiological results, and complications of minimally invasive reduction and fixation technique for ankle fractures type AO B. The surgical technique also is detailed.Material and Methods: A prospective analysis of 451 patients undergoing surgery for type AO B displaced ankle fracture was performed. All patients were treated with minimally invasive surgery. The following times were recorded: time between trauma and osteosynthesis, hospitalization length, surgical time, and exposure time to fluoroscopy. Age and gender, mechanism of injury, and characteristics of fractures were recorded. For functional outcome, AOFAS score, VAS, and Weber score were used. Radiographic analysis was performed. The average follow-up was 112 months.Results: Mean age was 48.2 years old. Average length of stay in hospital was 5.72 h. Mean duration of the surgery was 32.8 min. Average fluoroscopic exposure time during surgery was 9.25 s. Mean bone union time was 38.2 days. Weber's score was on average 1.5/24 points and the long-term follow-up AOFAS score was on average 97.5/100. Postoperative complications incidence was 2.7%.Conclusions: Distal fibula fixation with the MIPO technique presented good functional outcomes and could be helpful in the avoidance of the complications associated with conventional open reduction and internal fixation. However, it needs more exposition to intraoperative fluoroscopy.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

Introduction: Hip fractures are a pathology that have emerged as a major subject over the years, due to increased prevalence and the multiple surgical treatments involved. The characterization and classification of the lesion is essential for proper surgical planning, with anteroposterior (AP), lateral and traction radiograph of the hip, paramount for decision-making.Patients and Methods: This is a retrospective concordance study of 64 patients with hip fracture who consulted the hospital between January and July 2017. Four radiographs were taken of each: AP, AP with traction, lateral and lateral with traction. This set of images was evaluated by 9 observers, with different levels of experience, to answer questions regarding the classification, emphasize in potential instability and requirement of other images. A statistical analysis of concordance between and within observers was performed using Cohen's kappa coefficient.Results: Of the 64 patients, 70.6% were women; the average age was 69.5 years. 82.8% presented a secondary fracture from falling from their own height. As the observer's experience increases, the need for traction radiograph decreases; interobserver kappa goes from 0.98 in experts to 0.01 in students. Traction radiograph is important in the diagnosis of potentially unstable fractures. Of the 1,503 radiographs with traction, 636 (42.38%) were classified as potentially unstable. And of the 708 without traction, 560 (79.1%) were classified as potentially unstable.Conclusions: Traction hip radiograph continues to be a useful tool in training environments to adequately classify an intertrochanteric fracture, considering it is a low-cost, minimal morbidity intervention, and is easily accessible. In similar studies, we found similar findings regarding the usefulness of traction to perform an adequate classification in people in training or in young orthopedists. It also influences to determine the potential instability, and this would modify the choice of the implant. [ABSTRACT FROM AUTHOR]

Addressing major bone injuries is a challenge in bone regeneration, necessitating innovative 3D hydrogel-based therapeutic approaches to enhance scaffold properties for better bioactivity. Bacterial cellulose (BC) is an excellent scaffold for bone tissue engineering due to its biocompatibility, high porosity, substantial surface area, and remarkable mechanical strength. However, its practical application is limited due to a lack of inherent osteogenic activity and biomineralization ability. In this study, we synthesized bone-like apatite in biocompatible BC hydrogel by introducing phosphate groups. Hydrogels were prepared using fibrous BC, acrylamide (AM), and bis [2-methacryloyloxy] ethyl phosphate (BMEP) as a crosslinker through free radical polymerization (P-BC-PAM). P-BC-PAM hydrogels exhibited outstanding compressive mechanical properties, highly interconnected porous structures, good swelling, and biodegradable properties. BMEP content significantly influenced the physicochemical and biological properties of the hydrogels. Increasing BMEP content enhanced the fibrous structure, porosity from 85.1 % to 89.5 %, and compressive mechanical strength. The optimized hydrogel (2.0P-BC-PAM) displayed maximum compressive stress, toughness, and elastic modulus at 75 % strain: 221 ± 0.08 kPa, 24,674.2 ± 978 kPa, and 11 ± 0.47 kPa, respectively. P-BC-PAM hydrogels underwent biomineralization in simulated body fluid (SBF) for 14 days, forming bone-like apatite with a Ca/P ratio of 1.75, similar to hydroxyapatite. Confirmed by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and field-emission scanning electron microscopy (FE-SEM), this suggests their potential as scaffolds for bone tissue engineering. MC3T3-E1 osteoblast cells effectively attached and proliferated on P-BC-PAM. In summary, this study contributes insights into developing phosphate-functionalized BC-based hydrogels with potential applications in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Rhizoma Drynariae , as the dried rhizome of Drynaria fortunei (Kunze ex Mett.) J. Sm., is a traditional Chinese medicine for treating the injury and bone broken of falling and beating. Total flavonoids is considered as the major and effective compounds for the therapeutic efficacy of Rhizoma Drynariae. To explore the effect of total flavonoids from Rhizoma Drynariae (TFRD) on bone regeneration and the underlying mechanisms. The effect of TFRD in various doses on bone reconstruction in cranial bone defect rats was explored in vivo. The active ingredients in TFRD-medicated serum were characterized by serum pharmacochemistry and integrated by network pharmacology analysis and target prediction. To elucidate the underlying mechanism of TFRD on bone regeneration, experimental validation in vitro was executed to assess the influence of different concentrations of TFRD-medicated serum on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Micro-CT, histological examination, immunohistochemical analysis, and ELSA demonstrated that administration of TFRD could promote bone reconstruction in a rat cranial defect model. We identified 27 active components of TFRD using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Results from CCK8, ALP, and Alizarin Red S staining revealed that TFRD-medicated serum notably enhanced BMSCs proliferation and osteogenic differentiation. qRT-PCR and Western blot harvested results consistent with those predicted by network pharmacology, providing further evidence that TFRD activated the TGF-β signaling pathway to benefit bone regeneration. The active components of TFRD modulate the TGF-β signaling pathway to facilitate osteogenesis, thereby repairing cranial bone defects. [Display omitted] Total flavonoids from Rhizoma Drynariae enhances cranial bone regeneration. Employing serum pharmacochemistry investigation. Network pharmacology approaches investigation. [ABSTRACT FROM AUTHOR]

Regenerative repair of craniomaxillofacial bone injuries is challenging due to both the large size and irregular shape of many defects. Mineralized collagen scaffolds have previously been shown to be a promising biomaterial implant to accelerate craniofacial bone regeneration in vivo. Here we describe inclusion of a 3D-printed polymer or ceramic-based mesh into a mineralized collagen scaffold to improve mechanical and biological activity. Mineralized collagen scaffolds were reinforced with 3D-printed Fluffy-PLG (ultraporous polylactide-co-glycolide co-polymer) or Hyperelastic Bone (90wt% calcium phosphate in PLG) meshes. We show degradation byproducts and acidic release from the printed structures have limited negative impact on the viability of mesenchymal stem cells. Further, inclusion of a mesh formed from Hyperelastic Bone generates a reinforced composite with significantly improved mechanical performance (elastic modulus, push-out strength). Composites formed from the mineralized collagen scaffold and either Hyperelastic Bone or Fluffy-PLG reinforcement both supported human bone-marrow derived mesenchymal stem cell osteogenesis and new bone formation. This was observed by increased mineral formation in Fluffy-PLG composites and increased cell viability and upregulation of RUNX2, Osterix, and COL1A2 genes in both composites. Strikingly, composites reinforced with Hyperelastic Bone mesh elicited significantly increased secretion of osteoprotegerin, a soluble glycoprotein and endogenous inhibitor of osteoclast activity. These results suggest that architectured meshes can be integrated into collagen scaffolds to boost mechanical performance and actively instruct cell processes that aid osteogenicity; specifically, secretion of a factor crucial to inhibiting osteoclast-mediated bone resorption. Future work will focus on further adapting the polymer mesh architecture to confer improved shape-fitting capacity as well as to investigate the role of polymer reinforcement on MSC-osteoclast interactions as a means to increase regenerative potential. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Safeguarding, the action taken to protect children from harm, is an important aspect of paediatric care. Orthopaedic surgeons are often the first healthcare professionals to suspect physical abuse or non-accidental injury (NAI) on the basis of children presenting with unexplained bony injury. Physical harm from inflicted injury, a concept that most orthopaedic surgeons are familiar with, is not the only cause for a safeguarding referral and a comprehensive assessment may reveal concerns regarding: neglect, emotional abuse or sexual abuse. Clinicians caring for children, have to consider all of these factors as a cause for concern and organize onward referral. This article focuses on inflicted skeletal injury, how to recognize and investigate it. Typical fractures of concern are discussed and illustrated along with consideration of differential diagnoses. [ABSTRACT FROM AUTHOR]

• Cadmium attenuates the osteogenesis of hBMSCs. • Cadmium induced the blockage of ARL6 and Wnt/β-catenin pathway and the increase of miR-143-3p, which targeted ARL6 in hBMSCs. • ARL6 is involved in the cadmium-induced blockage of the Wnt/β-catenin pathway and the suppression of osteogenesis by hBMSCs. • miR-143-3p via ARL6 is involved in cadmium suppression of the Wnt/β-catenin pathway and osteogenic differentiation of hBMSCs. Cadmium, which is extensively distributed in the environment, accumulates in organisms through the trophic chain. Although cadmium can cause bone injury, its role in osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) remains unclear. The present study investigated the effect of cadmium chloride (CdCl 2) on osteogenesis of hBMSCs and the underlying mechanism. CdCl 2 dose-dependently reduced the viability of hBMSCs. Concentrations of CdCl 2 (2.5 and 5.0 μM) increased miR-143-3p levels; decreased levels of adenosine diphosphate-ribosylation factor-like protein 6 (ARL6); inhibited Wnt family member 3A (Wnt3a), β-catenin, lymphoid enhancer factor (LEF1), and T-cell factor 1 (TCF1); and suppressed osteogenesis of hBMSCs. Inhibition of miR-143-3p or overexpression of ARL6 with lentivirus blocked these CdCl 2 -induced changes. Luciferase reporter assays confirmed that miR-143-3p binds to the 3'-UTR regions of ARL6 mRNA. Reduced-expression of miR-143-3p enhanced the CdCl 2 -induced suppression of the osteogenesis of hBMSCs and inhibition of the Wnt/β-catenin pathway, effects that were reversed by down-regulated expression of ARL6. Thus, miR-143-3p targets ARL6 to down-regulate the Wnt/β-catenin pathway, which is involved in the suppression of osteogenic differentiation of hBMSCs. The results provide new directions for clinical treatment of bone diseases resulting from cadmium toxicity. [ABSTRACT FROM AUTHOR]

Introduction: Pes cavovarus is a three-dimensional (3D) foot deformity. New 3D semi-automatic measurements utilising weightbearing computerised topography (WBCT) images have recently been proposed to assess hindfoot alignment, but reliability in pes cavovarus has never been investigated. The aim of this study was to assess intraobserver and interobserver reliability of the foot ankle offset (FAO), calcaneal offset (CO) and hindfoot alignment angle (HAA) in pes cavovarus.Methods: Anonymised WBCT datasets from 51 feet (17 Charcot-Marie-Tooth related cavovarus, 17 idiopathic cavovarus and 17 controls) were retrospectively reviewed. Three observers (two senior foot and ankle fellows and one orthopaedic resident) independently measured FAO, CO and HAA using dedicated software, with measurements repeated two weeks apart. Subgroup analysis was performed to assess whether aetiology or severity of varus deformity and level of seniority affected reliability.Results: Mean values for intra and interobserver reliability for FAO (r=0.98; ICC: 0.99), CO (r=0.97; ICC: 0.98) and HAA measurements (r=0.97; ICC: 0.98) were excellent. Subgroup analyses showed that FAO, CO and HAA's intra (r/ρ range, 0.77-0.95) and interobserver (ICC range, 0.88-0.98) reliability remained excellent in patients with Charcot-Marie-Tooth related cavovarus, idiopathic pes cavovarus and normal feet, regardless of the severity of deformity. No difference was found in FAO, CO and HAA mean values from three observers (p>0.05 in all cases).Discussion: This study demonstrates that 3D semi-automatic measurements of WBCT images have excellent intra and interobserver reliability in the assessment of hindfoot alignment in pes cavovarus. Aetiology and severity of deformity, and level of seniority do not affect reliability of these measurements.Level Of Evidence: Level III, retrospective comparative study. [ABSTRACT FROM AUTHOR]

• Toll-Like Receptor 4, Autophagy and Bone Metabolism. This study aimed to elucidate the mechanism of autophagy in bone metabolism in high-glucose environments and its relationship with Toll-like receptor 4 (TLR4). A TLR4 knockout diabetic rat model and MC3T3-E1 with TLR4 silencing by small interfering RNA were used to observe the protective mechanism of TLR4 knockdown or silencing in hyperglycemia-induced bone injury. The inhibition of TLR4 expression improved bone metabolism and bone structure; promoted alkaline phosphatase (ALP) and osteocalcin (OCN) secretion, enhanced bone morphogenic protein (BMP)-2 expression, promoted bone mineralization, and reduced hyperglycemia-induced osteoblast apoptosis. TLR4 knockdown or silencing reduced the levels of inflammatory factors interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha at the animal and cell levels, inhibited the expression of inflammatory pathway proteins, and downregulated the expression of Beclin 1 and LC3II/LC-1 proteins. The inhibition of autophagic activity enhanced the osteoprotective effect of TLR4 knockdown, improved cell viability, reduced the apoptosis rate of osteoblasts, and promoted the BMP-2 protein level and ALP and OCN secretion. Conversely, the activation of autophagy significantly aggravated osteoblast apoptosis, reduced BMP-2 protein levels, and inhibited ALP and OCN secretion. Taken together, the experimental results supported the hypothesis that TLR4 deficiency might alleviate hyperglycemia-induced apoptosis and differentiation suppression in osteoblasts and exert osteoprotective effects via autophagic inhibition. [ABSTRACT FROM AUTHOR]

Background: Traumatic fractures are common in sub-Saharan Africa, a region with a shortfall of orthopaedic surgeons, and can result in morbidity if not appropriately managed. WhatsApp is an encrypted smartphone application and ubiquitous in sub-Saharan Africa. The objective of this study was to assess the use of WhatsApp as a mobile health platform to support fracture management by non-orthopaedic doctors in Cape Town, South Africa.Study Design: A WhatsApp orthopaedic referral group was created between non-orthopaedic doctors from community health clinics and the orthopaedic team from a first-level hospital to manage traumatic fractures. Non-orthopaedic doctors posted cases on the orthopaedic referral group and the orthopaedic team provided advice. Traumatic fracture data from January 1 to June 30, 2018 were analyzed and outcomes included response time, management advice, and treatment by facility level.Results: Seventy-two non-orthopaedic doctors posted 731 cases of traumatic fractures to the 5-member orthopaedic team. Six hundred and sixty-one (90%) cases were responded to within 1 hour. Three hundred and fifty-four (48%) patients were treated successfully by non-orthopaedic doctors at community health clinics, 288 (39%) were treated by the orthopaedic team at the first-level hospital, and 89 (12%) were referred directly to an orthopaedic subspecialist at a third-level hospital.Conclusions: The WhatsApp orthopaedic referral group provided a free telementoring platform for non-orthopaedic doctors to successfully manage traumatic fracture cases at community health clinics. This type of mobile health platform can be applicable to other resource-limited settings if disease burden is high and specialists are scarce. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) induces an acute alteration in bone metabolism. Although the aetiology of the bone disturbances is not precisely known, immobilisation reduces mechanical loading and the morphology of osteocytes, which are the primary mechanosensors. Periostin and sclerostin are secreted mostly by osteocytes and are involved in bone's mechanical response. The present study was conducted to determine whether individuals with SCI present alterations in serum periostin and sclerostin and to assess their relationships with bone mineral density, bone turnover markers, fracture status, time since injury, densitometric osteoporosis and paraplegic vs. tetraplegic status. One hundred and thirty-one individuals with SCI (96 males and 35 females; 42.8 ± 13.7 yr old) with a mean 14.2 ± 12.1 years since the time of injury were evaluated and compared with 40 able-bodied controls in a cross-sectional study. Periostin and sclerostin were assayed by ELISA from Biomedica® (Vienna, Austria), and bone turnover markers and areal bone mineral density (aBMD) were concomitantly analysed. Compared with controls, individuals with SCI presented higher periostin (p < 0.01), lower sclerostin (p < 0.001), similar markers of bone turnover levels and lower aBMD at the hip. Compared with chronic individuals, bone turnover markers, sclerostin excepted, values were higher as well as aBMD at hip in individuals with acute SCI. Moreover, the aBMD differences were more marked in tetraplegic than paraplegic individuals. Bone mineral density, fracture status, densitometric osteoporosis and paraplegia vs. tetraplegia did not seem to substantially influence the values of biological markers, sclerostin excepted. This study showed for the first time that individuals with SCI presented higher periostin levels than healthy controls only during the acute phase. Conversely, sclerostin levels are lower whatever the post-injury time. Fractures and densitometric osteoporosis were not associated with differences in these two biological markers, whereas paraplegia vs. tetraplegia and fragility fracture status seemed to influence sclerostin levels only. • Individual with SCI presented higher serum periostin levels in the acute phase and a normal values in the chronic phase. • Serum sclerostin levels were suppressed whatever the post-injury duration in the individuals with SCI. • Osteoporosis was not associated with periostin or sclerostin levels. • Paraplegia vs. tetraplegia and fragility fracture status seemed to influence sclerostin levels only. [ABSTRACT FROM AUTHOR]

It is essential to know the quantitative interactions between biological tissues and external mechanical and chemical stimuli. This assists the physicians to better know the quantitative behavior of the tissue and plan more effective therapy. In the literature, the effect of the chemical and mechanical loading was investigated on the bone biological cell activities and some mechanical features, but a lack of prediction of bone injury under the chemical and mechanical factors was sensed. Therefore, the present study aims to investigate the effects of the application of major chemical factors involved in ossification, including RANKL 1 1 Receptor Activator of Nuclear Factor Kappa Beta Ligand. (Receptor Activator of Nuclear Factor Kappa Beta Ligand), PTH 2 2 Parathyroid Hormone. (Parathyroid Hormone), and OPG 3 3 Osteoprotegerin. (Osteoprotegerin) on the mandibular bone biological osteoblast and osteoclast activities and mechanical properties. Moreover, the study assesses the bone injury possibility under uniform mastication pressure applied on the premolar tooth in terms of the mechanostat theory undergoing the effects of the chemical factors. A 3D geometry of the mandible-tooth assembly was generated from the CT image dataset. The geometry was next purified, solidified, and exported to FEM 4 4 Finite Element Method. (Finite Element Method) software to be meshed, where boundary conditions and loading were applied. Moreover, the mathematical system of differential equations to model the chemical factor effects on osteoblast and osteoclast activities as well as bone matrix volume fraction and elastic stiffness relations were applied. Next, the values of the equivalent strain were calculated to predict the injury states of the bone. The results complied with the literature data. The results showed that RANKL and PTH increased the values of the equivalent strain from 450 με to 11500 με, while OPG reduced that from 450 με to 300 με. Therefore, RANKL and PTH doses of this study put the bone at risk of injury compared to the baseline of no dose applied, while OPG secured the bone from injury. [Display omitted] • The effects of major chemicals were investigated on the mandible bone. • Mathematical and finite element approachs were used. • Osteoblast and osteoclast populations were calculated. • Bone matrix volume fraction and elastic moduli were calculated. • The risky factors of bone injury were determined. [ABSTRACT FROM AUTHOR]

The role of bone marrow mesenchymal stem cells (BMSCs) in treating radiation-induced brain injury (RIBI) is not completely understood, and assessment methods to directly characterize neurological function are lacking. In this study, we aimed to evaluate the effects of BMSCs treatment on changes in hippocampal neural function in Sprague–Dawley(SD) rats with RIBI, and to evaluate the therapeutic effect of BMSCs by manganese-enhanced magnetic resonance imaging (MEMRI). First, we assessed cognitive function after RIBI treatment with BMSCs using the Morris water maze. Next, we used MEMRI at two time points to observe the treatment effect and explore the correlation between MEMRI and cognitive function. Finally, we evaluated the expression of specific hippocampal neurofunctional proteins, the ultrastructure of hippocampal nerves, and the histological changes in the hippocampus. After BMSCs treatment of RIBI, cognitive dysfunction improved significantly, the expression of hippocampal neurofunctional proteins was increased, the integrity of the hippocampal neural structure was protected, and nerve cell survival was enhanced. The improvement in neurological function was successfully detected by MEMRI, and MEMRI was highly correlated with cognitive function and histological changes. These results suggest that BMSCs treatment of RIBI is an optional modality, and MEMRI can be used for treatment evaluation. • Bone marrow mesenchymal stem cells can repair hippocampus nerve damage caused by radiation-induced brain injury. • Cognitive function and pathological changes in radiation-induced brain injury are highly correlated with MEMRI. • MEMRI can sensitively detect neural damage in radiation-induced brain injury at both 3 h and 24 h. [ABSTRACT FROM AUTHOR]

Spinal traumas represent a significant proportion of muscle-skeletal injuries worldwide. Spinal injuries involve a complex structure with components having different traumatic susceptibility and variable healing capabilities. The interaction of numerous variables at time of trauma creates a great variety of lesions which makes challenging the creation and comparison of homogeneous groups, with difficulties in classifying spinal lesions, in assessing their instability, and in defining the indication and outcome of different treatment strategies. The evolution of concepts on instability has accompanied that of traumas classification schemes and treatment strategies. The assessment of instability in a spinal injury is actually crucial in front of newer surgical techniques and hardwares. Despite a long history of attempts to classify spinal traumas, it remains some degree of controversy in describing imaging data and a wide variety of treatment strategies. Acute cervical spine injuries affect from 1.9% to 4.6% of subjects reporting a blunt trauma, and up to 5.9% of multiple-injured patients. Most of spinal cord injuries are a consequence of unstable fractures of the cervical spine. An accurate and early diagnosis is mandatory to prevent neurological damage in unstable fractures. Classic and newer classifications are primarily based on features identifiable by using conventional imaging and CT scan, which are the most available modalities at most trauma centers. Even though multidetector-CT remains superior in assessing with high accuracy bone injuries, MRI is the most sensitive modality for detecting soft tissues injuries and spinal cord damage. [ABSTRACT FROM AUTHOR]

Forensic pathology and forensic anthropology are inherently related fields. The observations made during the autopsy and the conclusions from the anthropological analysis highlight the complementarities between the two approaches. In this review, gunshot wounds, sharp force injuries, chop wounds, blunt trauma, burned bodies, mechanical asphyxia and dismemberment will be analyzed from both perspectives. The result of this systematic review is that the conclusions stemming from the presence or absence of bone injuries must be very cautious because the observation of severe bone lesions does not always mean that this trauma was the cause of death; conversely, traumatic death, and even homicide, can be associated with a complete absence of bone lesions. [ABSTRACT FROM AUTHOR]

Introduction: Tarsometatarsal joint complex (TMC) is the anatomical structure of midfoot composed by metatarsals, tarsometatarsal (TMT) joints, cuneiforms, cuboid and navicular. TMC lesion are rare but critical since they cause severe disability if misdiagnosed. The knowledge of anatomic pattern of the lesion and biomechanics of the midfoot is the key for a successful diagnosis and treatment. The aim of this study was to review a consecutive series of TMC injuries analyzing preoperative radiograph and CT scan to accurately define the pattern of ligament and bone injuries.Material and Methods: We reviewed a series of 24 complete TMC injuries with homolateral dorsolateral dislocation. The total TMT joints involved were 120. We observed if the lesions were pure ligamentous or fracture-dislocation detecting the extent and the location of fractures. Twenty-nine lesions (24%) were pure dislocations and they were mainly localized in the first and fifth ray. The fracture-dislocations were 91 (76%) and 25 were fractures of the proximal row (cuneiforms and cuboid), 39 of the distal row (metatarsals), 27 of both the distal and proximal row.Results: Proximal fracture had a homogeneous distribution and they were more frequently simple than comminuted. Comminuted fractures were more frequent in the cuboid. In the proximal row, majority of partial articular fractures were localized in the dorsal side. Fracture-dislocations of the distal row were more frequent in the second metatarsal base (100%) and the partial articular fractures were always placed in the plantar side. In TMC injuries fracture-dislocations are more frequent than pure dislocations. Pure dislocations occur more often in the marginal rays that are characterized by weaker ligaments and larger mobility. The second ray, where there is the more stable joint of TMC, was never dislocated with a pure ligamentous lesion.Conclusions: We suppose that plantar avulsion from the distal row and dorsal compression fracture of the proximal row is consistent with a direct force applied to the forefoot and direct dorsolaterally. The direction of the forces may explain why some fractures occur in the distal row, some in the proximal and some in both rows. The thickness of plantar ligaments may explain the frequency of plantar bone fragment avulsion. [ABSTRACT FROM AUTHOR]

Sharp force trauma (SFT) in bone and cartilage has been studied extensively. This literature review summarizes knife and saw mark research. Researchers have documented several features of cut surfaces and successfully associated them with various tool characteristics. Most study designs are based on light microscopic examination, but other technologies such as micro-computed scanning, scanning electron microscope, and epifluorescence microscopy have been investigated. Researchers have worked with human and non-human material, and found that the presentation of SFT differs between the two. Furthermore, they have designed studies to control the parameters surrounding SFT (e.g., tool angle, force, direction) as well as not to control these parameters (real-world scenario) and have found that the trauma produced in the two scenarios differ considerably. Researchers have attempted to calculate the error rate associated with cut and saw mark analysis and have reported very different results. Several high profile cases of successful SFT analysis have been published and are briefly reviewed. Expert testimony based on cut and saw mark analysis has been found admissible, but not in all cases. Unfortunately, researchers have not consistently used standard terminology, a list of terms gathered from the literature is provided. Despite the extensive research, more work is needed. Methods that mitigate potential sources of error that are not dependent on analyst's experience must be developed. [ABSTRACT FROM AUTHOR]

Blunt traumas are the most common injuries observed and reported in medical examiner settings. Two common methods to describe bending bone fractures in the anthropological literature include the application of morphology nomenclature and describing characteristic fracture morphology. A nomenclature descriptor of blunt trauma, the butterfly fracture, is commonly used to describe broken long bones. In this paper, a case study of a fractured long bone in a pedestrian vehicle accident is used to highlight the complex interplay of factors involved in bone fracture formation. The application of a butterfly fracture pattern in trauma analysis is useful in establishing the bending direction of a bone, in identifying failure modes, and is valuable in teaching. Yet, butterfly fracture characteristics need to be examined in 3-dimensions for diagnosis of modes of failure, tension, shear and compression, and even then, the bending direction of a broken bone may not provide a reliable indicator of the point of impact (POI); this is especially true when a priori knowledge of the injury is unknown. Common fracture nomenclature, such as oblique, transverse and/or comminuted, as well as eponyms, are medical descriptions of an injury which are impractical to use for interpreting a broken bone from fleshed or skeletonized remains, in establishing a POI and in evaluating total bone trauma (TBT). The examination ofcharacteristic features on the surface of a broken bone associated with the modes of failure is the best approach for establishing the bending direction of a long bone. [ABSTRACT FROM AUTHOR]

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]

Abstract Mesenchymal stem cells (MSCs) have gained increasing attention as a potential approach for the treatment of bone injuries due to their multi-lineage differentiation potential and also their ability to recognize and home to damaged tissue sites, secreting bioactive factors that can modulate the immune system and enhance tissue repair. However, a wide gap between the number of MSCs obtainable from the donor site and the number required for implantation, as well as the lack of understanding of MSC functions under different in vitro and in vivo microenvironment, hinders the progression of MSCs toward clinical settings. The clinical translation of MSCs pre-requisites a scalable expansion process for the biomanufacturing of therapeutically qualified cells. This review briefly introduces the features of implanted MSCs to determine the best strategies to optimize their regenerative capacity, as well as the current MSC implantation for bone diseases. Current achievements for expansion of MSCs using various culturing methods, bioreactor technologies, biomaterial platforms, as well as microtissue-based expansion strategies are also discussed, providing new insights into future large-scale MSC expansion and clinical applications. [ABSTRACT FROM AUTHOR]

Background: Even though the number of patients with cervical spinal cord injury (CSCI) without major bone injury is increased, the treatment with either surgery or conservative measures remains controversial. The aim of this study was to assess its prognostic value in the prediction of useful motor recovery and to clarify whether the patients should be treated surgically are present.Methods: We reviewed 63 patients (conservative, n = 36; surgery, n = 27) with CSCI without major bone injury (Frankel A-C). Neurological examination using modified Frankel grade at admission and 6 months after injury and International Stoke Mandeville Games (ISMG) classification at subacute phase after injury, MRI findings including rate of spinal cord compression, extent of cord damage and type of signal intensity change were assessed.Results: Thirty-five of 63 patients were improved to walk at 6 months after injury. In multivariate analysis, rate of spinal cord compression, extent of cord damage and improvement of ISMG grade were associated with useful motor recovery. There was no difference in the neurological improvement between conservative and surgical groups. However, patients with spinal cord compression of ≥33.2% showed better motor recovery at 6 months post-injury after surgery than those treated conservatively. There was a positive correlation between the improvement of ISMG grade at subacute phase and Frankel grade at 6 months post-injury. It is difficult to obtain satisfactory surgical outcome for patients with Frankel A or B1 on admission and/or extensive spinal cord damage on T2-weighted image.Conclusions: Conservative treatment is recommended for patients with CSCI without major bone injury. However, we also recommend surgical treatment to acquire walking ability for patients with spinal cord compression of ≥33.2% and low ISMG grade at subacute phase. Among such patients, careful consideration should be given to patients with Frankel A or B1 and/or extensive spinal cord damage on MRI. [ABSTRACT FROM AUTHOR]

Abstract Bone is a complex hierarchal structured material with varying porosity and mechanical properties. In particular, human cranial bone is essentially a natural composite consisting of low porosity outer and inner tables and a cancellous interior, or diploë. Experimental studies of biomechanically accurate cranial bone analogues are of high importance for biomechanical, forensics, and clinical researchers, which could improve the understanding and prevention of traumatic injury. Many reported studies use commercially available bone surrogates to draw biomechanical and forensics conclusions; however, their mechanical properties are not tabulated over a range of strain rates. This study elucidates the mechanical viability of three leading commercially available bone surrogates, i.e. Synbone, Sawbone, and Bonesim, over a large range of strain rates (10−3 to 103 s−1). Quasi-static compression testing was conducted using a universal testing machine and a Split-Hopkinson Pressure bar system equipped with high-speed video was used to determine the dynamic mechanical behavior of these materials. Micro-computed X-ray tomography (XRT) were performed on each material to investigate their pore structures and distributions. All materials exhibited strain rate dependent strength behavior, particularly at high loading rates (≥103 s−1). The Young's modulus was found to increase with strain rate from 10−3 to 10−1 s−1 for transversely and longitudinally loaded surrogate materials except for Synbone and the higher density Bonesim. The higher density Bonesim was determined to be the most suitable cranial bone simulant tested based on a combination of transverse Young's Modulus (1500 MPa), yield strength (19 MPa), ultimate strength (49 MPa), and ultimate strain (17%). These materials show limited promise for applications where the measured elastic properties and strengths are of interest. [ABSTRACT FROM AUTHOR]

Highlights • Possible bio- applications of bistable glass-coated microwires are shown. • Biocompatibility was proven experimentally. • Application on temperature sensing in cranium implants is confirmed. • Application for osteomalacy monitoring is shown. Abstract In the given contribution, two examples of applications of glass-coated microwires for biomedical sensing are shown. Firstly, application of microwires for contactless sensing of the intracranial temperature below titanium implants confirms the possibility to sense the temperature with sensitivity down to 0.01 °C. Secondly, application of microwires for monitoring the stress applied on bones after injury or for monitoring the osteomalacy effect is shown. Our measurements confirm that high sensitivity of order of 10−10 s/Pa can be obtained. [ABSTRACT FROM AUTHOR]

There is a significant unmet clinical need for modular and customized porous biodegradable constructs (scaffolds) for non-union large bone loss injuries. This paper proposes modelling and biomanufacturing of modular and customizable porous constructs for patient-specific critical bone defects. A computational geometry-based algorithm was developed to model modular porous constructs using a parametric femur model based on the frequency of common injuries. The generated modular constructs are used to generate biomimetic path planning for three-dimensional (3D) printing of modular scaffold pieces. The developed method can be used for regenerating bone tissue for treating non-union large bone defects. [ABSTRACT FROM AUTHOR]

Background: Open articular fractures are an important issue due to their increasing incidence, along with the rise in motorcycle accidents. Oncology experience with allograft in orthopedics may be extended to cases of traumatic bone loss.Clinical Case: A 37-year-old man with an open fracture of the distal femur and proximal tibia presented a massive bone loss of the lateral femoral condyle after a motorcycle accident. Following Damage Control Surgery, a considerable lateral femoral condyle allograft was used to restore the joint anatomy.Results: After an intensive rehabilitation program and two subsequent arthroscopic arthrolyses, the patient resumed walking without aids and recovered from stiffness (R.O.M. 0-130°). An MRI performed at median follow-up, revealed a favorable integration of the allograft.Discussion: Allografts are a reasonable reconstructive option for young individuals with massive bone loss. An appropriately sized allograft is essential to restore an acceptable function as seen in the herein case. [ABSTRACT FROM AUTHOR]

Surgical approach selection and fixation of Hoffa fractures is difficult and remains controversial. Evolving trends emphasize the importance of fracture morphology, fracture location, and comminution, all of which guide decisions regarding surgical approach and implant selection. This focused review highlights factors affecting Hoffa fracture available surgical approaches, treatment outcomes, and recommendations for selecting an optimal approach. [ABSTRACT FROM AUTHOR]

Abstract Background Healthy cartilage is essential for optimal joint function. Although, articular cartilage defects are highly prevalent in the active population and hamper joint function, the effect of articular cartilage defects on knee loading is not yet documented. Therefore, the present study compared knee contact forces and pressures between patients with tibiofemoral cartilage defects and healthy controls. Potentially this provides additional insights in movement adaptations and the role of altered loading in the progression from defect towards OA. Methods Experimental gait data collected in 15 patients with isolated cartilage defects (8 medial involvement, 7 lateral-involvement) and 19 healthy asymptomatic controls was processed using a musculoskeletal model to calculate contact forces and pressures. Differences between two patient groups and controls were evaluated using Kruskal-Wallis tests and individually compared using Mann-Whitney- U tests (alpha <0.05). Findings The patients with lateral involvement walked significantly slower compared to the healthy controls. No movement adaptations to decrease the loading on the injured condyle were observed. Additionally, the location of loading was not significantly affected. Interpretation The current results suggest that isolated cartilage defects do not induce significant changes in the knee joint loading distribution. Consequently, the involved condyle will capture a physiological loading magnitude that should however be distributed over the cartilage surrounding the defect. This may cause local degenerative changes in the cartilage and in combination with inflammatory responses, might play a key role in the progression from articular cartilage defect to a more severe OA phenotype. Highlights • Cartilage defects did not affect gait kinematics and kinetics of the lower limbs. • Compartmental loading is not altered in presence of an isolated cartilage defect. • Changes in the surrounding cartilage may contribute to osteoarthritis progression. [ABSTRACT FROM AUTHOR]

Introduction: There is a lack of epidemiological studies of fractures in all segments of the tibia classified by orthopaedic surgeons according to the AO/OTA classification. Since 2011, the Swedish Fracture Register (SFR) has provided prospectively collected, population-based data on fractures of all types, treated both surgically and non-surgically. The aim of this study was to describe the epidemiology and incidence of fractures in all segments of the tibia in a cohort of consecutive tibia fractures over a period of five years at Sahlgrenska University Hospital, Gothenburg, Sweden.Methods: Information on age, gender, date and mechanism of injury, fracture classification according to AO/OTA, affected side and high- or low-energy trauma was extracted from the SFR for all patients, aged 16 years and above, with tibia fractures treated at Sahlgrenska University Hospital, Gothenburg, during the five-year period 1 January 2011 to 31 December 2015.Results: 1325 patients sustained 1371 tibia fractures. There were 712 proximal tibia fractures, 417 tibial shaft fractures and 242 distal tibia fractures. Patients with proximal tibia fractures had a higher mean age (54.3) and 58% were women, whereas patients with shaft and distal fractures had a slightly lower mean age (47.0 and 48.7 respectively) and a dominance of men (59% and 54% respectively). The overall incidence of tibia fractures was 51.7 per 100,000 and year. The incidence of proximal, diaphyseal and distal tibia fractures was 26.9, 15.7 and 9.1 respectively per 100,000 and year. Among women, tibia fractures showed an increasing incidence with age in all segments, whereas men had a fairly flat incidence curve, except for tibial shaft fractures, which displayed a peak among young males. The incidence of tibia fractures and graphs for age-specific incidence for each segment of the tibia are presented.Conclusions: This study describes the epidemiology and incidence of fractures in the whole of the tibia classified by orthopaedic surgeons according to the AO/OTA classification. [ABSTRACT FROM AUTHOR]

Abstract Background aims Regenerative medicine strategies based on cell therapy are considered a promising approach to repair bone defects. The aims of this study were to evaluate the effect of subculturing on the osteogenic potential of osteoblasts derived from newborn rat calvaria and the effect of these osteoblasts on bone repair of rat calvaria defects. Methods Cells were obtained from 50 newborn rat calvaria, and primary osteoblasts (OB) were compared with first passage (OB-P1) in terms of osteogenic potential by assaying cell proliferation, alkaline phosphatase (ALP) activity, extracellular matrix mineralization and gene expression of the osteoblastic markers RUNX2, ALP, osteocalcin and bone sialoprotein. Then, 5-mm calvaria defects were created in 24 Wistar rats, and after 2 weeks, they were locally injected with 50 µL of phosphate-buffered saline containing either 5 × 106 osteoblasts (OB-P1, n = 12) or no cells (control, n = 12). Four weeks post-injection, the bone formation was evaluated by micro-computed tomography and histological analyses. Data were compared by analysis of variance, followed by the Student-Newman-Keuls's test or Student's t -test (P ≤ 0.05). Results OB-P1 showed high proliferation and ALP activity, and despite the reduced gene expression of osteoblastic markers and extracellular matrix mineralization compared with OB, they displayed osteogenic potential, being a good choice for injection into calvaria defects. The micro-tomographic and histological data showed that defects treated with OB-P1 presented higher bone formation compared with control defects. Discussion Our results indicate that cells derived from newborn rat calvaria retain osteoblastic characteristics after subculturing and that these osteoblasts stimulate bone repair in a rat calvaria defect model. [ABSTRACT FROM AUTHOR]

• Construction workers sustain a disproportionate number of severe work-related injuries. • Current investigation examined over 11,000 injuries reported via the severe injury reporting program. • Findings reveal overrepresented event types, injury sources, injured body parts, injury nature, and sectors. • Findings also reveal relationship between injury attributes. • Results can be leveraged to enhance work-related safety among construction workers. Construction workers sustain a large number of work-related injuries. These injuries sometimes result in irreversible damage, life-long disability, and even the loss of life. Therefore, strategic initiatives to reduce work-related injuries are necessary. To help achieve this goal, the Occupational Safety and Health Administration (OSHA) recently introduced a new severe injury reporting program. The program requires that employers notify OSHA of any severe or serious injuries that result in amputation, in-patient hospitalization, or loss of an eye within 24 h. The current investigation statistically examined more than 11,000 physical injuries reported as part of this program to identify patterns and discover opportunities to enhance workplace safety. The key findings include: (1) the most commonly reported severe injury event types are falls to lower level and struck-by object or equipment incidents; (2) the most commonly reported injury sources are ladders and structural elements such as joists, roofs, and skylights; (3) the most commonly reported injured body parts are the upper extremities and the lower extremities ; (4) the most commonly reported nature of injuries are traumatic injuries to bones, nerves, and spinal cord (e.g., fractures) and open wounds ; (5) the most reportedly vulnerable construction sectors for severe injuries are commercial and institutional building construction and electrical contractors and other wiring installation contractors. The findings also offer insights into the relationship between injury attributes. For example, the event type " falls to lower level" was particularly likely when workers used the injury source "ladders per the data." The findings can be leveraged to enhance work-related safety among construction workers. [ABSTRACT FROM AUTHOR]

Abstract Purpose The aim of this study was to investigate the influence of human bone marrow−derived endothelial progenitor cells (EPC) on vascularization and bone regeneration in combination with a bone-substitute material (BSM) in a critical-size bone defect in a murine model. Critical-size bone defects were performed and the defects were filled according to the group membership. Materials and methods Eighteen rats were randomized in two experimental groups: BSM (BoneCeramic) with/without EPC biofunctionalization, and a control group without BSM and EPC. Calvaria bone defects were performed and the defects were filled according to the group membership. After 8 weeks, qualitative tissue response of newly formed bone mass was analyzed by histology, cone beam CT (CBCT) and micro-CT (μCT) scans. Occurrence of tumor masses due to EPC vascularization in peripheral organs was investigated microscopically in histological slides of liver and kidney. Results The combination of EPC and BSM showed smaller bone defects in the CT scans and the histological evaluation as the single use of BSM without EPC by trend (p = 0.067). Further, a higher amount of blood vessels could be found in histological slices of BSM in combination with EPC. No inflammatory response or tumor formation could be found. Conclusion These findings confirm the biocompatibility of the used BSM and provide evidence that the combination of BSM with EPC might be effective for bone vascularization and regeneration. Using EPC in augmentation sites might overall lead to faster and better bone regeneration and should be further investigated in future studies. Highlights • Biofunctionalization of bone substitutes might improve bone regeneration. • Endothelial progenitor cells (EPC) have a strong angiogenic potency. • Combination of bone substitutes and EPC can accelerate bone regeneration. • Combination of bone substitutes and EPC can accelerate bone vascularization. • EPC might be suitable for biofunctionalization of bone substitutes. [ABSTRACT FROM AUTHOR]

Abstract Purpose The aims of this study were as follows: To determine the national incidence of facial fractures among infants, toddlers, and children; to evaluate the types of facial fractures; and to analyze common products/activities associated with the fractures. Materials and methods A retrospective review was conducted to explore patterns of facial fractures among infants (<1 year), toddlers (1–3 years), and children (3–5 years), using the National Electronic Injury Surveillance System (NEISS) from the Consumer Product Safety Commission (CPSC). The database was searched for emergency department (ED) visits involving facial fractures sustained by children 1 month through 5 years of age from 2004 through 2016 and analyzed for patient demographics, primary diagnosis and associated products/activities. Subset analyses were performed between age groups to determine the relationship between causes of injury and age using extrapolated national incidences. Results A total of 1507 ED visits for facial fractures among infants, toddlers, and children were obtained and extrapolated to an estimated total of 39,388 ED visits, averaging 3030 annually. The majority of these ED visits were for facial fractures that occurred at home. Most facial fractures sustained at the age period of 1 month–5 years old were nasal fractures. Facial fractures in infants were caused most commonly by floors or flooring materials, likely due to falls, while household items/furniture-related injuries were the most common cause of facial fractures in both toddlers and children. Facial fractures from playground equipment and riding toys were more common in children than in the other age groups. Conclusion The reported trends in the incidence by age group and types of fracture can assist physicians by serving as supplement for clinical history and examination when encountering this challenging patient population. Our findings highlight preventative opportunities, particularly in baby care items and beds for reducing facial fractures in infants. Similarly, preventative opportunities are highlighted in household items and furniture for lowering the incidence of facial fractures in toddlers and children. Our study also suggests ensuring safe handling of playground equipment and riding toys for the prevention of facial fractures in children. [ABSTRACT FROM AUTHOR]

Subchondral bone injury due to high magnitude and repetition of compressive loading is common in humans and athletic animals such as Thoroughbred racehorses. Repeated loading of the joint surface may alter the subchondral bone microstructure and initiate microdamage in the bone adjacent to the articular cartilage. Understanding the relationship between microdamage, microstructure and mechanical properties of the subchondral bone adjacent to the articular cartilage is, therefore, essential in understanding the mechanism of subchondral bone injury. In this study, we used high-resolution µCT scanning, a digital image-based strain measurement technique, and mechanical testing to evaluate the three-dimensional pre-existing microcracks, bone volume fraction (BVF) and bone mineral density (BMD), and mechanical properties (stiffness and hysteresis) of subchondral bone (n = 10) from the distopalmar aspect of the third metacarpal (MC3) condyles of Thoroughbred racehorses under high-rate compression. We specifically compared the properties of two regions of interest in the subchondral bone: the 2 mm superficial subchondral bone (SSB) and its underlying 2 mm deep subchondral bone (DSB). The DSB region was 3.0 ± 1.2 times stiffer than its overlying SSB, yet it dissipated much less energy compared to the SSB. There was no correlation between structural properties (BVF and BMD) and mechanical properties (stiffness and energy loss), except for BMD and energy loss in SSB. The lower stiffness of the most superficial subchondral bone in the distal metacarpal condyles may protect the overlying cartilage and the underlying subchondral bone from damage under the high-rate compression experienced during galloping. However, repeated high-rate loading over time has the potential to inhibit bone turnover and induce bone fatigue, consistent with the high prevalence of subchondral bone injury and fractures in athletic humans and racehorses. [ABSTRACT FROM AUTHOR]

Although an understanding of bone material properties is crucial for interpreting and predicting fracture patterns due to injury or defining the effects of disease on bone strength, information about infant bone properties is scant in the literature. In this study we present the mechanical testing results from 47 tibia and 52 rib specimens taken from 53 infant decedents in order to further our understanding of infant bone strength. Bone specimens were imaged using microCT and tested in three-point bending until failure. Extrinsic and intrinsic properties demonstrated an increase in strength and stiffness over the first year of life, while ductility measures remained largely unchanged. Donor race had no effect on the material properties, but tibia bone specimens showed significant sex differences, with the elastic modulus from females being larger than males. When compared to properties from adolescent and adult donors, infant bone is less strong, less stiff, and more ductile. [ABSTRACT FROM AUTHOR]

Background: With the increasing aging population in developed countries, there has been an associated increased prevalence of osteoporotic vertebral fracture (OVF). Many previous reports have attempted to predict the risk of delayed union associated with OVF. However, the role of endplate failure and the degeneration of adjacent intervertebral discs, and their association with delayed union has received little attention. The aim of this study was to evaluate the endplate fracture and disc degeneration rank as risk factors for delayed union.Materials and Methods: Two hundred and eighteen consecutive patients with fresh OVF were enrolled in the study. MRI and X-ray were performed at the time of enrollment and at the 6 months follow-up. The MR images were used to assess the degeneration grade of adjacent intervertebral discs (using the modified Pfirrmann grading system), and endplate failure. Supine and weight-bearing radiographs were used to define angular motion and compression ratio of the anterior vertebral body wall.Results: A total of 139 patients (112 female, 27 male) completed the 6 month follow-up (a 65.1% follow-up rate). The study revealed 27 cases of delayed union (19.4%). A healthier adjacent caudal disc with low grade degeneration was found to be associated with an increased risk of delayed union (P = 0.008). Bi-endplate injury and significant compression of the anterior vertebral body wall were significantly associated with delayed union (P = 0.019, and P = 0.001 respectively). Rapid progression of the adjacent cranial disc degeneration was observed at the end of the 6 month follow-up period (P = 0.001).Conclusion: Modified Pfirrmann grading system revealed that a healthier adjacent intervertebral disc at the caudal level and bi-endplate fracture were significantly associated with an increased risk of delayed union. These findings may influence the management strategy for patients with OVF. [ABSTRACT FROM AUTHOR]

Whole-bone analyses can obscure regional heterogeneities in bone characteristics. Quantifying these heterogeneities might improve our understanding of the etiology of injuries, such as lower-extremity stress fractures. Here, we performed regional analyses of high-resolution peripheral quantitative computed tomography images of the ultradistal tibia in young, healthy subjects (age range, 18 to 30 years). We quantified bone characteristics across four regional sectors of the tibia for the following datasets: white women (n = 50), black women (n = 51), white men (n = 50), black men (n = 34), and all subjects (n = 185). After controlling for potentially confounding variables, we observed statistically significant variations in most of the characteristics across sectors (p < 0.05). Most of the bone characteristics followed a similar trend for all datasets but with different magnitudes. Regardless of race or sex, the anterior sector had the lowest trabecular and total volumetric bone mineral density and highest trabecular separation (p < 0.001), while cortical thickness was lowest in the medial sector (p < 0.05). Accordingly, the anterior sector also had the lowest elastic modulus in the anterior-posterior and superior-inferior directions (p < 0.001). In all sectors, the mean anisotropy was ~3, suggesting cross-sector similarity in the ratios of loading in these directions. In addition, the bone characteristics from regional and whole-bone analyses differed in all datasets (p < 0.05). Our findings on the heterogeneous nature of bone microarchitecture in the ultradistal tibia may reflect an adaptation of the bone to habitual loading conditions. [ABSTRACT FROM AUTHOR]