Very fast, high-resolution aggregation 3D detection CAM to quickly and accurately find facial fracture areas.

BACKGROUND AND OBJECTIVE: The incidence of facial fractures is on the rise globally, yet limited studies are addressing the diverse forms of facial fractures present in 3D images. In particular, due to the nature of the facial fracture, the direction in which the bone fractures vary, and there is no clear outline, it is difficult to determine the exact location of the fracture in 2D images. Thus, 3D image analysis is required to find the exact fracture area, but it needs heavy computational complexity and expensive pixel-wise labeling for supervised learning. In this study, we tackle the problem of reducing the computational burden and increasing the accuracy of fracture localization by using a weakly-supervised object localization without pixel-wise labeling in a 3D image space. METHODS: We propose a Very Fast, High-Resolution Aggregation 3D Detection CAM (VFHA-CAM) model, which can detect various facial fractures. To better detect tiny fractures, our model uses high-resolution feature maps and employs Ablation CAM to find an exact fracture location without pixel-wise labeling, where we use a rough fracture image detected with 3D box-wise labeling. To this end, we extract important features and use only essential features to reduce the computational complexity in 3D image space. RESULTS: Experimental findings demonstrate that VFHA-CAM surpasses state-of-the-art 2D detection methods by up to 20% in sensitivity/person and specificity/person, achieving sensitivity/person and specificity/person scores of 87% and 85%, respectively. In addition, Our VFHA-CAM reduces location analysis time to 76 s without performance degradation compared to a simple Ablation CAM method that takes more than 20 min. CONCLUSION: This study introduces a novel weakly-supervised object localization approach for bone fracture detection in 3D facial images. The proposed method employs a 3D detection model, which helps detect various forms of facial bone fractures accurately. The CAM algorithm adopted for fracture area segmentation within a 3D fracture detection box is key in quickly informing medical staff of the exact location of a facial bone fracture in a weakly-supervised object localization. In addition, we provide 3D visualization so that even non-experts unfamiliar with 3D CT images can identify the fracture status and location.

A protocol to differentiate the chondrogenic ATDC5 cell-line for the collection of chondrocyte-derived extracellular vesicles.

Skeletal growth and fracture healing rely on the mineralization of cartilage in a process called endochondral ossification. Chondrocytes firstly synthesize and then modify cartilage by the release of a wide range of particles into their extracellular space. Extracellular vesicles (EVs) are one type of such particles, but their roles in endochondral ossification are yet to be fully understood. It remains a challenge to obtain representative populations of chondrocyte-derived EVs, owing to difficulties both in preserving the function of primary chondrocytes in culture and in applying the serum-free conditions required for EV production. Here, we used the ATDC5 cell-line to recover chondrocyte-derived EVs from early- and late-differentiation stages, representing chondrocytes before and during cartilage mineralization. After screening different culture conditions, our data indicate that a serum-free Opti-MEM-based culture medium preserves chondrocyte identity and function, matrix mineralization and cell viability. We subsequently scaled-up production and isolated EVs from conditioned medium by size-exclusion chromatography. The obtained chondrocyte-derived EVs had typical ultrastructure and expression of classical EV markers, at quantities suitable for downstream experiments. Importantly, chondrocyte-derived EVs from late-differentiation stages had elevated levels of alkaline phosphatase activity. Hence, we established a method to obtain functional chondrocyte-derived EVs before and during cartilage mineralization that may aid the further understanding of their roles in endochondral bone growth and fracture healing.

Fracture risk prediction in diabetes patients based on Lasso feature selection and Machine Learning.

Fracture risk among individuals with diabetes poses significant clinical challenges due to the multifaceted relationship between diabetes and bone health. Diabetes not only affects bone density but also alters bone quality and structure, thereby increases the susceptibility to fractures. Given the rising prevalence of diabetes worldwide and its associated complications, accurate prediction of fracture risk in diabetic individuals has emerged as a pressing clinical need. This study aims to investigate the factors influencing fracture risk among diabetic patients. We propose a framework that combines Lasso feature selection with eight classification algorithms. Initially, Lasso regression is employed to select 24 significant features. Subsequently, we utilize grid search and 5-fold cross-validation to train and tune the selected classification algorithms, including KNN, Naive Bayes, Decision Tree, Random Forest, AdaBoost, XGBoost, Multi-layer Perceptron (MLP), and Support Vector Machine (SVM). Among models trained using these important features, Random Forest exhibits the highest performance with a predictive accuracy of 93.87%. Comparative analysis across all features, important features, and remaining features demonstrate the crucial role of features selected by Lasso regression in predicting fracture risk among diabetic patients. Besides, by using a feature importance ranking algorithm, we find several features that hold significant reference values for predicting early bone fracture risk in diabetic individuals.

Artificial intelligence applications in bone fractures: A bibliometric and science mapping analysis.

Background: Bone fractures are a common medical issue worldwide, causing a serious economic burden on society. In recent years, the application of artificial intelligence (AI) in the field of fracture has developed rapidly, especially in fracture diagnosis, where AI has shown significant capabilities comparable to those of professional orthopedic surgeons. This study aimed to review the development process and applications of AI in the field of fracture using bibliometric analysis, while analyzing the research hotspots and future trends in the field. Materials and methods: Studies on AI and fracture were retrieved from the Web of Science Core Collections since 1990, a retrospective bibliometric and visualized study of the filtered data was conducted through CiteSpace and Bibliometrix R package. Results: A total of 1063 publications were included in the analysis, with the annual publication rapidly growing since 2017. China had the most publications, and the United States had the most citations. Technical University of Munich, Germany, had the most publications. Doornberg JN was the most productive author. Most research in this field was published in Scientific Reports. Doi K's 2007 review in Computerized Medical Imaging and Graphics was the most influential paper. Conclusion: AI application in fracture has achieved outstanding results and will continue to progress. In this study, we used a bibliometric analysis to assist researchers in understanding the basic knowledge structure, research hotspots, and future trends in this field, to further promote the development of AI applications in fracture.

Advanced glycation end products mediate biomineralization disorder in diabetic bone disease.

Patients with diabetes often experience fragile fractures despite normal or higher bone mineral density (BMD), a phenomenon termed the diabetic bone paradox (DBP). The pathogenesis and therapeutics opinions for diabetic bone disease (DBD) are not fully explored. In this study, we utilize two preclinical diabetic models, the leptin receptor-deficient db/db mice (DB) mouse model and the streptozotocin-induced diabetes (STZ) mouse model. These models demonstrate higher BMD and lower mechanical strength, mirroring clinical observations in diabetic patients. Advanced glycation end products (AGEs) accumulate in diabetic bones, causing higher non-enzymatic crosslinking within collagen fibrils. This inhibits intrafibrillar mineralization and leads to disordered mineral deposition on collagen fibrils, ultimately reducing bone strength. Guanidines, inhibiting AGE formation, significantly improve the microstructure and biomechanical strength of diabetic bone and enhance bone fracture healing. Therefore, targeting AGEs may offer a strategy to regulate bone mineralization and microstructure, potentially preventing the onset of DBD.

Long-term outcomes after capitate fractures: a median 16-year follow-up.

INTRODUCTION: The long-term effects of a capitate fracture are unknown. The aim of this study was to assess both clinical and radiological long-term outcomes after a capitate fracture. MATERIALS AND METHODS: From a cohort of 526 consecutive patients with post traumatic radial sided wrist pain, 23 were identified diagnosed with a capitate fracture. 16 of these (11 males and 5 females) with a median age at injury of 17.5 years (range 11-27 years) were eligible for a follow-up after a median of 16 years (range 8 to 17 years). In this study patients were examined using conventional radiographs, computed tomography (CT) and magnetic resonance imaging (MRI) at the time of injury and with CT at the follow-up. At follow-up radiological signs of osteoarthritis were graded in four stages and clinical outcome was evaluated by measuring range of wrist motion and grip and pinch strength. The subjective outcome was assessed using DASH and PRWE questionnaires. RESULTS: Five patients had isolated capitate fractures and 11 had concomitant fractures, 10 of which had a simultaneous scaphoid fracture. 14 patients had been treated non-surgically in a cast and two patients were treated surgically. None of the fractures were visible on conventional radiographs at the time of injury. At follow-up all fractures had healed without signs of avascular necrosis. In one patient, CT examination revealed osteoarthritis between the capitate and lunate. This did not cause clinical symptoms. Functional impairments and pain scores were low: median DASH score 0, median PRWE 3 and median VAS pain score 0. We found no impairment in range of motion or grip and pinch strength. CONCLUSIONS: At a median of 16-year follow-up, patients with a capitate fracture report normal self-assessed hand function as well as good wrist motion and strength. The risk of development of posttraumatic arthritis in the joints around the capitate is low.

Toward Fully Automated Personalized Orthopedic Treatments: Innovations and Interdisciplinary Gaps.

Personalized orthopedic devices are increasingly favored for their potential to enhance long-term treatment success. Despite significant advancements across various disciplines, the seamless integration and full automation of personalized orthopedic treatments remain elusive. This paper identifies key interdisciplinary gaps in integrating and automating advanced technologies for personalized orthopedic treatment. It begins by outlining the standard clinical practices in orthopedic treatments and the extent of personalization achievable. The paper then explores recent innovations in artificial intelligence, biomaterials, genomic and proteomic analyses, lab-on-a-chip, medical imaging, image-based biomechanical finite element modeling, biomimicry, 3D printing and bioprinting, and implantable sensors, emphasizing their contributions to personalized treatments. Tentative strategies or solutions are proposed to address the interdisciplinary gaps by utilizing innovative technologies. The key findings highlight the need for the non-invasive quantitative assessment of bone quality, patient-specific biocompatibility, and device designs that address individual biological and mechanical conditions. This comprehensive review underscores the transformative potential of these technologies and the importance of multidisciplinary collaboration to integrate and automate them into a cohesive, intelligent system for personalized orthopedic treatments.

Bone Imaging of the Knee Using Short-Interval Delta Ultrashort Echo Time and Field Echo Imaging.

Background: Computed tomography (CT) is the preferred imaging modality for bone evaluation of the knee, while MRI of the bone is actively being developed. We present three techniques using short-interval delta ultrashort echo time (δUTE), field echo (FE), and FE with high resolution-deep learning reconstruction (HR-DLR) for direct bone MRI. Methods: Knees of healthy volunteers (n = 5, 3 females, 38 ± 17.2 years old) were imaged. CT-like images were generated by averaging images from multiple echoes and inverting. The bone signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were determined. Results: The δUTE depicted a cortical bone with high signal intensity but could not resolve trabeculae. In contrast, both the FE and FE HR-DLR images depicted cortical and trabecular bone with high signal. Quantitatively, while δUTE had a good bone SNR of ~100 and CNR of ~40 for the cortical bone, the SNR for the FE HR-DLR was significantly higher (p < 0.05), at over 400, and CNR at over 200. Conclusions: For 3D rendering of the bone surfaces, the δUTE provided better image contrast and separation of bone from ligaments and tendons than the FE sequences. While there still is no MRI technique that provides a perfect CT-like contrast, continued advancement of MRI techniques may provide benefits for specific use cases.

Prevention of Adhesions after Bone Fracture Using a Carboxymethylcellulose and Polyethylene Oxide Composite Gel in Dogs.

The formation of adhesions is a common complication following traumatic injuries and surgical procedures, often resulting in pain, stiffness, and loss of function. This study aimed to evaluate the feasibility and safety of using a composite material comprising of carboxymethylcellulose (CMC), polyethylene oxide (PEO), and calcium chloride, for preventing adhesions between muscle and bone during the healing stage, as well as its effect on the bone healing process. Ten healthy purpose-bred laboratory Beagle dogs were randomly subjected to two consecutive operations with a 6-month interval, alternating between left and right forelimbs. On the left forelimb an osteotomy at the ulna was performed, while on the right forelimb the same procedure was supplemented by the application of the anti-adhesion agent in the osteotomy site prior to closure. Clinical, diagnostic imaging, macroscopic, and histological evaluations were performed at various time points. The results showed no significant differences in surgical site perimeter (p = 0.558), lameness (p = 0.227), and radiographic bone healing (p = 0.379) between the two groups. However, the macroscopic (p = 0.006) and histological assessments revealed significantly lower adhesion scores (p = 0.0049) and better healing (p = 0.0102) in the group that received the anti-adhesion agent. These findings suggest that the CMC/PEO composite material is a safe and potentially effective intervention for preventing post-traumatic and post-surgical adhesions in canine patients without compromising bone healing. Further research is warranted to fully characterize the clinical benefits of this approach.

Bone Tissue Changes in Individuals Living with HIV/AIDS: The Importance of a Hierarchical Approach in Investigating Bone Fragility.

Skeletal alterations and their complications can significantly impact the quality of life and overall prognosis of patients living with HIV (PLWHIV). Considering skeletal alterations are often asymptomatic and unapparent during routine clinical evaluation, these conditions are frequently overlooked in the clinical management of PLWHIV. However, since the use of combined antiretroviral therapy (cART) has increased life expectancy in PLWHIV effectively, osteopenia, osteoporosis, and bone fragility are now considered to have a major health impact, with a substantial increase in healthcare costs. This narrative literature review aimed to provide a comprehensive overview of the contemporary literature related to bone changes in PLWHIV, focusing on the importance of taking a multi-scale approach in the assessment of bone hierarchical organization. Even though a low bone mineral density is frequently reported in PLWHIV, numerous ambiguities still remain to be solved. Recent data suggest that assessment of other bone properties (on various levels of the bone structure) could contribute to our understanding of bone fragility determinants in these individuals. Special attention is needed for women living with HIV/AIDS since a postmenopausal status was described as an important factor that contributes to skeletal alterations in this population. Further research on complex etiopathogenetic mechanisms underlying bone alterations in PLWHIV may lead to the development of new therapeutic approaches specifically designed to reduce the health burden associated with skeletal disorders in this population. A major challenge in the clinical management of PLWHIV lies in the adverse skeletal effects of some frequently prescribed cART regimens (e.g., regimens containing tenofovir disoproxil fumarate), which may require a switch to other pharmacological approaches for maintained HIV infection (e.g., regimens containing tenofovir alafenamide). Taken together, the findings are indicative that the HIV/AIDS status should be taken into consideration when designing new guidelines and strategies for individualized prevention, diagnosis, and treatment of increased bone fragility.

Outcome and Management of Occipitofrontal Contrecoup Head Injury.

Contrecoup brain injury refers to the classical opposite of the primary impact. Tamil Nadu has the highest rate of road traffic accident in India. Madurai has peak mortality due to accidents in India. Previous studies done on contrecoup head injury had shown patterns of injuries and mechanism of injury. Outcome and management of only occipitofrontal contrecoup head injury has been taken in this study. Mortality in this specific group is very high. Seventy-six patients of this specific head injury were admitted at Government Rajaji Hospital, Madurai. Patients were assessed for Glasgow coma scale (GCS), age, sex, progression of volume, mortality, traumatic brain injury-induced coagulopathy, and pillion rider outcome. Fourteen patients were surgically treated by decompressive craniectomy. Conservative management was done by antiepileptic and antiedema measures. Mostly affected were males ( n = 54) followed by females ( n = 22). GCS on admission mean value 9. In our study, mortality was 32% with sudden death of three patients due to hypothalamic compression. Hospital stay of the patient was significantly increased with progression of lesion with mean 9 days and p -value less than 0.01. Pillion riders ( n = 18) were also affected in our study. Traumatic brain injury-induced coagulopathy ( n = 12) was also detected, which was treated by injection tranexamic acid and injection vitamin K, thereby not leading to any death due to coagulopathy with significant p -value less than 0.01. We recommend helmet for both main and pillion rider with strict speeding regulations.

Operative Management of Pediatric Physeal Bar Development and Genu Valgum.

Background: Pediatric orthopedic conditions present unique challenges due to ongoing skeletal growth and development. Managing these cases requires addressing both structural anomalies and functional deficits. Care presentation: This case report discusses a 13-year-old male with recurrent left knee pain exacerbated by physical activity. The patient's history of a left knee infection at 1.5 years of age, possibly septic arthritis or osteomyelitis, underscores the long-term consequences of early pathology on skeletal growth and alignment. Imaging studies revealed a distal lateral femur physis bar and genu valgum, necessitating surgical intervention. Management and Outcomes: The surgery involved medial distal femur hemiepiphysiodesis and lateral distal femur bar excision to correct anatomical deformities and restore optimal limb alignment and function. Postoperative rehabilitation, including targeted exercises to improve quadriceps strength, was crucial for functional recovery and reducing the risk of complications such as medial patellofemoral pain. Conclusion: This case highlights the importance of a multidisciplinary approach in managing complex pediatric orthopedic cases.

Adaptive Image Segmentation Reveals Substantial Cortical Bone Remodeling During Early Fracture Repair.

The goal of this study was to develop an image analysis algorithm for quantifying the effects of remodeling on cortical bone during early fracture healing. An adaptive thresholding technique with boundary curvature and tortuosity control was developed to automatically identify the endocortical and pericortical boundaries in the presence of high-gradient bone mineral density (BMD) near the healing zone. The algorithm successfully segmented more than 47,000 microCT images from 12 healing ovine osteotomies and intact contralateral tibiae. Resampling techniques were used to achieve data dimensionality reduction on the segmented images, allowing characterization of radial and axial distributions of cortical BMD. Local (transverse slice) and total (whole bone) remodeling scores were produced. These surrogate measures of cortical remodeling derived from BMD revealed that cortical changes were detectable throughout the region covered by callus and that the localized loss of cortical BMD was highest near the osteotomy. Total remodeling score was moderately and significantly correlated with callus volume and mineral composition (r > 0.64, p < 0.05), suggesting that the cortex may be a source of mineral needed to build callus.

Brain-Bone Crosstalk in a Murine Polytrauma Model Promotes Bone Remodeling but Impairs Neuromotor Recovery and Anxiety-Related Behavior.

Traumatic brain injury (TBI) and long bone fractures are a common injury pattern in polytrauma patients and modulate each other's healing process. As only a limited number of studies have investigated both traumatic sites, we tested the hypothesis that brain-bone polytrauma mutually impacts neuro- and osteopathological outcomes. Adult female C57BL/6N mice were subjected to controlled cortical impact (CCI), and/or osteosynthetic stabilized femoral fracture (FF), or sham surgery. Neuromotor and behavioral impairments were assessed by neurological severity score, open field test, rotarod test, and elevated plus maze test. Brain and bone tissues were processed 42 days after trauma. CCI+FF polytrauma mice had increased bone formation as compared to FF mice and increased mRNA expression of bone sialoprotein (BSP). Bone fractures did not aggravate neuropathology or neuroinflammation assessed by cerebral lesion size, hippocampal integrity, astrocyte and microglia activation, and gene expression. Behavioral assessments demonstrated an overall impaired recovery of neuromotor function and persistent abnormalities in anxiety-related behavior in polytrauma mice. This study shows enhanced bone healing, impaired neuromotor recovery and anxiety-like behavior in a brain-bone polytrauma model. However, bone fractures did not aggravate TBI-evoked neuropathology, suggesting the existence of outcome-relevant mechanisms independent of the extent of brain structural damage and neuroinflammation.

Finite element solution of coupled multiphysics reaction-diffusion equations for fracture healing in hard biological tissues.

This study proposes a computational framework to investigate the multi-stage process of fracture healing in hard tissues, e.g., long bone, based on the mathematical Bailon-Plaza and Van der Meulen formulation. The goal is to explore the influence of critical biological factors by employing the finite element method for more realistic configurations. The model integrates a set of variables, including cell densities, growth factors, and extracellular matrix contents, managed by a coupled system of partial differential equations. A weak finite element formulation is introduced to enhance the numerical robustness for coarser mesh grids, complex geometries, and more accurate boundary conditions. This formulation is less sensitive to mesh quality and converges smoothly with mesh refinement, exhibiting superior numerical stability compared to previously available strong-form solutions. The model accurately reproduces various stages of healing, including soft cartilage callus formation, endochondral and intramembranous ossification, and hard bony callus development for various sizes of fracture gap. Model predictions align with the existing research and are logically coherent with the available experimental data. The developed multiphysics simulation clarifies the coordination of cellular dynamics, extracellular matrix alterations, and signaling growth factors during fracture healing.

Comparing intravenous lidocaine and pethidine for pain management in emergency department patients with femoral bone fracture: a randomized controlled trial.

BACKGROUND: Intravenous lidocaine has shown promise as an effective analgesic in various clinical settings, but its utility for pain management in emergency departments, especially for bone fractures, remains relatively understudied. OBJECTIVE: This study compared intravenous lidocaine to pethidine for femoral bone fracture pain management. METHODS: This double-blind, randomized, controlled clinical trial was conducted in the emergency department of AJA University of Medical Sciences affiliated hospitals. Patients aged 18-70 years-old with femoral bone fracture and experiencing severe pain, defined as a numerical rating scale (NRS) of pain ≥ 7, were included in the study. One group received intravenous pethidine (25 mg), while the other group received intravenous lidocaine (3 mg/kg, not exceeding 200 mg), infused with 250 ml saline over 20 min. Pain levels were evaluated before treatment administration (0 min) and at 10, 20, 30, 40, 50, and 60 min after treatment administration using the NRS. RESULTS: Seventy-two patients were enrolled in the study. Demographic characteristics and pain scores were similar between the two groups. The mean pain scores upon arrival for the lidocaine and pethidine groups were 8.50 ± 1 and 8.0 ± 1, respectively; after one hour, they were 4.0 ± 1 and 4.0 ± 1, respectively. While there was a statistically significant reduction in pain in both groups after one hour, there were no clinically or statistically significant differences between the two groups (p = 0.262). Pethidine had a higher incidence of adverse events, though not statistically significant. Additionally, females required more rescue analgesics. CONCLUSION: The administration of intravenous lidocaine is beneficial for managing pain in femoral bone fractures, suggesting that lidocaine could be a potent alternative to opioids. TRIAL REGISTRATION: IRCT20231213060355N1 ( https://irct.behdasht.gov.ir/trial/74624 ) (30/12/2023).

Artificial Intelligence Application in Skull Bone Fracture with Segmentation Approach.

This study aims to evaluate an AI model designed to automatically classify skull fractures and visualize segmentation on emergent CT scans. The model's goal is to boost diagnostic accuracy, alleviate radiologists' workload, and hasten diagnosis, thereby enhancing patient outcomes. Unique to this research, both pediatric and post-operative patients were not excluded, and diagnostic durations were analyzed. Our testing dataset for the observer studies involved 671 patients, with a mean age of 58.88 years and fairly balanced gender representation. Model 1 of our AI algorithm, trained with 1499 fracture-positive cases, showed a sensitivity of 0.94 and specificity of 0.87, with a DICE score of 0.65. Implementing post-processing rules (specifically Rule B) improved the model's performance, resulting in a sensitivity of 0.94, specificity of 0.99, and a DICE score of 0.63. AI-assisted diagnosis resulted in significantly enhanced performance for all participants, with sensitivity almost doubling for junior radiology residents and other specialists. Additionally, diagnostic durations were significantly reduced (p < 0.01) with AI assistance across all participant categories. Our skull fracture detection model, employing a segmentation approach, demonstrated high performance, enhancing diagnostic accuracy and efficiency for radiologists and clinical physicians. This underlines the potential of AI integration in medical imaging analysis to improve patient care.

Bone Fracture Healing under the Intervention of a Stretchable Ultrasound Array.

Ultrasound treatment has been recognized as an effective and noninvasive approach to promote fracture healing. However, traditional rigid ultrasound probe is bulky, requiring cumbersome manual operations and inducing unfavorable side effects when functioning, which precludes the wide application of ultrasound in bone fracture healing. Here, we report a stretchable ultrasound array for bone fracture healing, which features high-performance 1-3 piezoelectric composites as transducers, stretchable multilayered serpentine metal films in a bridge-island pattern as electrical interconnects, soft elastomeric membranes as encapsulations, and polydimethylsiloxane (PDMS) with low curing agent ratio as adhesive layers. The resulting ultrasound array offers the benefits of large stretchability for easy skin integration and effective affecting region for simple skin alignment with good electromechanical performance. Experimental investigations of the stretchable ultrasound array on the delayed union model in femoral shafts of rats show that the callus growth is more active in the second week of treatment and the fracture site is completely osseous healed in the sixth week of treatment. Various bone quality indicators (e.g., bone modulus, bone mineral density, bone tissue/total tissue volume, and trabecular bone thickness) could be enhanced with the intervention of a stretchable ultrasound array. Histological and immunohistochemical examinations indicate that ultrasound promotes osteoblast differentiation, bone formation, and remodeling by promoting the expression of osteopontin (OPN) and runt-related transcription factor 2 (RUNX2). This work provides an effective tool for bone fracture healing in a simple and convenient manner and creates engineering opportunities for applying ultrasound in medical applications.

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

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

Stretchable Ultrasound Metalens for Biomedical Zoom Imaging and Bone Quality Assessment with Subwavelength Resolution.

Ultrasound imaging is extensively used in biomedical science and clinical practice. Imaging resolution and tunability of imaging plane are key performance indicators, but both remain challenging to be improved due to the longer wavelength compared with light and the lack of zoom lens for ultrasound. Here, the ultrasound zoom imaging based on a stretchable planar metalens that simultaneously achieves the subwavelength imaging resolution and dynamic control of the imaging plane is reported. The proposed zoom imaging ultrasonography enables precise bone fracture diagnosis and comprehensive osteoporosis assessment. Millimeter-scale microarchitectures of the cortical bones at different depths can be selectively imaged with a 0.6-wavelength resolution. The morphological features of bone fractures, including the shape, size and position, are accurately detected. Based on the extracted ultrasound information of cancellous bones with healthy matrix, osteopenia and osteoporosis, a multi-index osteoporosis evaluation method is developed. Furthermore, it provides additional biological information in aspects of bone elasticity and attenuation to access the comprehensive osteoporosis assessment. The soft metalens also features flexibility and biocompatibility for preferable applications on wearable devices. This work provides a strategy for the development of high-resolution ultrasound biomedical zoom imaging and comprehensive bone quality diagnosis system.