Athletic injury are caused by the trauma encountered during exercise, which can lead to different degrees of pain, mobility impairment, and even disability in severe cases. Currently, the traditional rehabilitation methods have limited efficacy and personalized treatment is insufficient. Brain-computer interface (BCI) technology provides a novel solution for the rehabilitation of patients with athletic injuries by establishing a direct communication and control channel between the brain and external device. BCI technology has unique advantages in motor function reconstruction, sensory loss improvement, and neuropathic pain regulation through motor intention decoding, neurofeedback, and artificial sensory feedback. BCI system involves three key aspects: brain signal acquisition, analysis and processing, and external device control and the integration of artificial intelligence (AI) provides new insights for signal analysis and processing in it. To further promote the development of new rehabilitation techniques, reduce treatment costs, and promote the overall rehabilitation of patients, the authors elaborated on the characteristics of BCI technology, existing problems in motor rehabilitation, and applications of BCI in athletic injury rehabilitation so as to provide reference and inspiration for researchers in related fields, accelerate innovation, breakthrough, transformation and application of BCI technology, and benefit more patients with athletic injuries.

Objective:To explore the clinical value of a trinity strategy for the treatment of multiple orthopedic trauma.Methods:A retrospective case series study was conducted to analyze the clinical data of 1 267 patients with multiple orthopedic trauma admitted to Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the First Affiliated Hospital of Navy Medical University from June 2013 to May 2023, including 862 males and 405 females, aged 18-93 years [(55.2±19.8)years]. Associated injuries included hemorrhagic shock in 632 patients, traumatic wet lung in 274, cranial injuries in 135, abdominal and pelvic bleeding in 116, pneumothorax in 89, urinary injury in 13, and vesical rupture in 8. All the patients were treated with the trinity strategy and the treatment process was divided into the phases of first aid, remodeling, and rehabilitation. The first aid phase focused on stabilizing symptoms and saving lives; the remodeling phase centered on restoring the anatomical structure and alignment; the rehabilitation phase aimed for functional recovery through the integration of both Western and traditional Chinese medicine. The all-cause mortality within 30 days after surgery and fracture healing time were calculated; the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, Hospital for Special Surgery (HSS) knee score and the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score at the last follow-up and the overall excellent and good rate of all joint function scores were measured. The short form health survey (SF-36) scores were collected preoperatively and at 6 months postoperatively, including 8 aspects such as physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health. The incidence of postoperative complications was recorded.Results:All the patients were followed up for 6-18 months [(10.2±4.2)months]. The mortality rate during the acute phase (within 30 days after surgery) was 2.37% with 12 deaths due to hemorrhagic shock, 10 due to traumatic brain injury, 6 due to multiple organ dysfunction syndrome (MODS), and 2 due to pulmonary infection. The average fracture healing time averaged 3.8-18 months [(11.5±4.2)months], with 89.49% of the patients having bone union within 12 months after surgery, 8.93% having bone union within 18 months after surgery, and 1.58% undergoing reoperation. For the patients with internal fixation failure and nonunion, the average healing time was extended to (10.2±2.2)months and (13.7±3.3)months respectively. At the last follow-up, the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, HSS knee score, and AOFAS ankle-hindfoot score were 83.93%, 90.24%, 94.12%, 85.57%, 88.46%, and 92.31% respectively, with an overall excellent and good rate of 89.11%. At 6 months after surgery, the SF-36 scores of all the patients in the eight dimensions,including the physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health were (74.4±8.6)points, (44.7±14.4)points, (77.4±10.9)points, (68.4±18.2)points, (72.5±16.0)points, (76.8±8.7)points, (49.9±17.6)points, and (72.8±17.9)points, significantly improved compared with those before operation [(63.4±12.7)points, (30.9±17.4)points, (56.4±18.0)points, (55.4±24.7)points, (53.5±21.0)points, (55.8±24.3)points, (36.9±24.0)points, (58.8±21.6)points] ( P<0.01). Complications of different degrees occurred in 214 patients (16.89%), including lung infections in 118 patients (9.31%), lower extremity deep vein thrombosis in 50(3.95%), pressure injuries in 26(2.05%), internal fixation failure in 12(0.95%), and nonunion in 8(0.63%). Conclusions:The trinity strategy provides whole-process management, personalized treatment, and overall rehabilitation for multiple orthopedic trauma. It can decrease mortality, shorten fracture healing time, improve joint function and quality of life, and reduce the incidence of complications.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

The diagnosis and treatment of motor system diseases are faced with some difficulties,such as unclear mechanism,low diagnostic efficiency,difficult model construction,slow drug development,and hard to bionic repair.Bone/cartilage organoids are a kind of tissue that can simulate the structure and function of bone/cartilage tissue by three-dimensional cultured cells in vitro.It provides a disruptive tool for research on bone/cartilage diseases and greatly revolutionize clinical diagnosis and treatment strategies in orthopedics.This paper systematically introduces the strategies and current research status of constructing bone/cartilage organoids to address the diagnostic and therapeutic dilemmas of bone/cartilage diseases.It proposes cutting-edge advancements that revolutionize clinical diagnosis and treatment strategies while summarizing the three stages of development from basic organoids,structured organoids to functionalized organoids.

Objective The aim of this study was to investigate the prospective association between physical activity (PA),independently or in conjunction with other contributing factors,and osteoporosis (OP) outcomes. Methods The Physical Activity in Osteoporosis Outcomes (PAOPO) study was a community-based cohort investigation. A structured questionnaire was used to gather the participants' sociodemographic characteristics. Bone mineral density (BMD) measurements were performed to assess OP outcomes,and the relationship between BMD and OP was evaluated within this cohort. Results From 2013 to 2014,8,471 participants aged 18 years and older were recruited from Tangshan,China's Jidong community. Based on their PA level,participants were categorized as inactive,moderately active,or very active. Men showed higher physical exercise levels than women across the activity groups. BMD was significantly higher in the very active group than in the moderately active and inactive groups. Individuals aged>50 years are at a higher risk of developing OP and osteopenia. Conclusion The PAOPO study offers promising insights into the relationship between PA and OP outcomes,encouraging the implementation of PA in preventing and managing OP.

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future.

Bone organoids are cellular structures cultured in vitro that can mimic the structure and function of real bone tissues. Currently, significant progress has been made in the researches of bone organoids, cartilage organoids, bone callus organoids, etc. These organoids can be constructed using combinations of stem cells or specific cell types and are characterized with the potential and function of osteogenesis. Despite the immense potential applications of bone organoids, their construction still faces several challenges. For instance, there are ongoing controversies regarding the types, sources, identification, and isolation methods of skeletal stem cells. Additionally, further research is needed to select and optimize extracellular matrices suitable for bone organoid construction. Vascularization of bone organoids is a crucial factor limiting their size. Meanwhile, breakthroughs in artificial intelligence technology offer new thoughts for the construction of bone organoids. Hurdles in fundamental researches and practical needs such as bone defect repair create new opportunities for the study of bone organoids. For this purpose, the authors systematically elucidated the current researches and challenges in the construction of bone organoids and discussed countermeasures to address these challenges, aiming to provide reference for researches and translational applications of bone organoids.

Objective:To construct a double-layer bone-on-a-chip containing bone matrix, with which the process of osteoblast and osteoclast differentiation in vitro is stimulated, aiming to provide a new platform for the development of osteoporosis medications. Methods:Software WorkSoild was used to design the double-layer and double-channel bone-on-a-chip and the template was fabricated by photolithography. With polydimethylsiloxane (PDMS) as the raw material, the main body of the chip was prepared by mold fabrication. The inlets and outlets of the four channels of the culture room were separated with bovine cortex bones and sealed with liquid storage columns. In the chip verification experiment, chips were divided into osteogenic and osteoclastic induction groups and osteogenic and osteoclastic control groups. In the osteogenic and osteoclastic induction groups, precursor cells of mouse embryonic osteoblast, MC3T3-E1 and mouse macrophage RAW264.7 were inoculated on the chip separately. Osteogenic induction lasted 14 days and osteoclastic induction 7 days. MC3T3-E1 cells and RAW264.7 cells were not induced in the osteogenic and osteoclastic control groups. The following indicators were observed: (1) Appearance and sealing performance of the chip: After the chip was prepared, photos were taken to observe its appearance and sealing tests were conducted to observe its sealing performance. (2) Biocompatibility: At 3 days after MC3T3-E1 cells were inoculated onto the chip and cultured and at 1, 3 and 5 days after RAW264.7 cells were inoculated onto the chip and cultured, the cell survival was observed with calcein acetoxymethyl ester/propidium iodide (AM/PI) staining and Cell Counting Kit 8 (CCK-8). (3) Osteogenic differentiation: Alkaline phosphatase (ALP) staining and alizarin red staining were performed on the cells in the osteogenic induction group to observe the osteogenic induction. RNA was collected from the osteogenic induction group and the osteogenic control group, the expression of osteoblast marker Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN) and type I collagen (COL1A1) was detected by real-time florescent quantitative PCR (qPCR), and the differentiation degree and osteogenic ability of osteoblasts were observed. (4) Osteoclast differentiation: tartrate-resistant acid phosphatase (TRAP) staining was performed on cells in the osteoclastic induction group to observe osteoclast differentiation. RNA was extracted from the osteoclastic induction group and the osteoclastic control group for qPCR of osteoclast differentiation-related genes, and the expression levels of the osteoclast marker gene TRAP, cathepsin K (CTSK) and dendritic cell specific transmembrane protein (DC-STAMP) were detected.Results:The double-layer bone-on-a-chip containing bone matrix was 3 cm×3 cm in size and transparent as a whole. The structure of the system on the chip system was compact and had no seepage. It was shown by calcein AM/PI staining that at 3 days after MC3T3-E1 cells and RAW264.7 cells were cultured, very few red fluorescent dead cells were found. CCK-8 test showed that within 5 days after being cultured, the cell viability was all above 90%, indicating that the biocompatibility of the chip was good and the cells could survive and proliferate normally. The results of ALP and alizarin red staining showed that MC3T3-E1 cells successfully differentiated into osteoblasts and produced calcified nodules in the osteogenic induction group at 14 days after the induction. The qPCR results showed that the relative expression level of RUNX2 in MC3T3-E1 cells in the osteogenic induction group was 4.98±0.74, which was significantly higher than that of the control group (0.99±0.03) ( P<0.01). The relative expression level of OCN in MC3T3-E1 cells was 7.98±0.76, which was significantly higher than that of the control group (1.00±0.06) ( P<0.01). The relative expression level of COL1A1 in MC3T3-E1 cells was 7.07±0.56, which was significantly higher than that of the control group (0.97±0.03) ( P<0.01). The TRAP staining results showed that the RAW264.7 cells in the osteoclastic induction group differentiated to giant multinucleated osteoclasts, and TRAP protein was expressed in large quantity in the osteoclasts. The results of qPCR showed that the relative expression level of TRAP in RAW264.7 cells in the osteoclastic induction group was 3.35±0.37, which was significantly higher than that of the control group (1.01±0.06) ( P<0.01). The relative expression level of CTSK in RAW264.7 cells was 3.46±0.79, which was significantly higher than that of the control group (1.01±0.05) ( P<0.01). The relative expression level of DC-STAMP in RAW264.7 cells was 1.92±0.12, which was significantly higher than that of the control group (0.98±0.08) ( P<0.01). Conclusions:The double-layer bone-on-a-chip containing bone matrix is compact in structure, can be cultured in vitro for a long time, has good biocompatibility and can be used for inducing osteogenic and osteoclast differentiation. Therefore, it is expected to provide a new research platform for exploring the mechanism of osteoporosis and medication screening.

Objective:To construct 3D-bioprinted organoid artificial skin derived from adult stem cells and investigate their effects on repair of skin defect in mice.Methods:The cell suspension mixture was prepared with human skin keratinocytes, fibroblasts and vascular endothelial cells with a ratio of 2∶1∶1 and cultured in ultra-low attachment plates, and morphological changes of cell spheres were observed with an inverted phase contrast microscope. After 7 days of culture, cell spheres were collected and immunofluorescence staining was performed to characterize the expression and structural distribution of the epidermis, dermis and blood vessels. The artificial skin composed of skin organoids were printed through 3D printing and morphology of printed artificial skin and dressing was observed. Ten immunodeficient balb/c female mice were divided into hydrogel group and organoid group, with 5 mice in each group with the method of random number table. The full-thickness skin defect model with a diameter of 1 cm was established in all mice, and the wound was covered with the hydrogel dressings in hydrogel group and with 3D-printed skin organoids of the same size in organoid group. Wound healing and healing rate of the two groups were observed at 0, 4, 8, 12 and 16 days after modeling. At 16 days after modeling, HE staining was performed on wound skin samples to observe the epidermal keratosis and dermal epidermal junction of the wound surface and Masson staining to observe the density of collagen fibers and dermal fiber thickness of the wound surface.Results:(1) The cell suspension mixture of keratinocytes, fibroblasts and vascular endothelial cells could self-aggregate into cell spheres in the ultra-low attachment plates, and it was observed with the inverted phase contrast microscope that the volume of cell spheres gradually increased with the extension of culture time. (2) Immunofluorescence staining of the cell spheres showed that epidermal markers such as keratin (K)1, K10, and K14 were expressed in the outer layer of the cell spheres, and dermal markers such as vimentin (VIM) and vascular markers CD31 were expressed in the core, which indicated the epidermis was located in the outer layer of the sphere, and the dermis and blood vessels were located in the core of the sphere, with the same structural characteristics of the skin organoids. (3) The 3D-printed organoid artificial skin and hydrogel dressing were round and transparent, with a diameter of 10 mm and a thickness of 1 mm. (4) As shown in the general observation of the wound surface, the wound area of both groups decreased with the extension of treatment time. The wound of the organoid group healed faster, which showed obvious epithelization at 4 days after modeling and basic wound healing at 16 days after modeling. At 0 day after modeling, there was no obvious difference in the appearance of wound surface between the two groups. At 4 and 8 days after modeling, the wound healing rates were (31.7±1.0)% and (52.4±5.4)% in the organoid group, and (24.3±6.8)% and (45.4±7.0)% in the hydrogel group ( P>0.05). At 12 and 16 days after modeling, the wound healing rates were (78.6±8.0)% and (91.1±5.6)% in the organoid group, and were (58.5±5.4)% and (71.9±7.8)% in the hydrogel group ( P<0.01). (5) HE staining showed that in the organoid group epidermal keratinization was found better, with the epidermis being more intact and well attached to the dermis. Epidermal keratinization was not complete in hydrogel group and the epidermis and dermis were obviously separated. Masson staining showed the formation of collagen fiber structures in the wound surface of both groups, which were blue and reticular. The collagen fiber structure was more compact and the dermal fiber thickness was smaller in the organoid group, while the collagen fiber structure was loose and the dermal fiber thickness was greater in the hydrogel group. Conclusions:Adult stem cells of skin can successfully form skin organoids in 3D culture conditions and organoid artificial skin can be constructed with 3D bioprinting technology. Compared with hydrogel dressing, 3D-bioprinted organoid artificial skin can significantly improve the healing rate in mice, with better epidermal keratinization and closer attachment of the epidermis to the dermis. Moreover, the collagen fiber structure of the wound is more compact, with smaller dermal fiber in thickness.

Large skin defect caused by severe trauma is a common clinical problem with high incidence, great harm, difficult treatment and poor prognosis, which not only seriously affects the quality of patients′ life, but also threatens their lives. Large skin defects are difficult to heal by themselves and the main treatment is skin transplantation. However, the source of the autologous flap is limited and may cause secondary damage to patients. The artificial skin has poor mechanical integrity that cannot be integrated, causing formation of scars, and also has the risk of immune rejection. Skin organoid technology can extremely simulate the human skin tissue and its functions. Thus, it can overcome the shortcomings of the current skin wound treatment to a certain extent and provide a new treatment for the patients with large skin defects. At present, the construction methods of skin organoids are relatively mature, but each method has its advantages and disadvantages, and the best method has not been determined yet. Moreover, the structure and function of skin organoids are relatively simple, so there is still a relatively big gap between skin organoids and real human skin. Hence, the authors reviewed the research progress in skin organoid construction strategies from organoids′ skin organoid technology, and construction methods of skin organoids, hoping to provide a reference for the construction of skin organoids with more complex structures and functions in the future.