Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design

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.

432A perspective on light-based bioprinting of DNA hydrogels for advanced bone regeneration: Implication for bone organoids.

Light-based three-dimensional (3D) printing of hydrogels has been widely adopted for accelerating bone regeneration. However, the design principles of traditional hydrogels do not take into consideration the biomimetic regulation of multiple stages throughout the bone healing, and the hydrogels made cannot effectively induce sufficient osteogenesis, which in turn greatly limits their capacity in guiding bone regeneration. The recent progress achieved in DNA hydrogel, which is based on synthetic biology, could facilitate the innovation of the current strategy due to its advantages, such as resistance to enzymatic degradation, programmability, structural controllability, and mechanical properties. However, 3D printing of DNA hydrogel is not well defined and appears to have a few distinct early forms. In this article, a perspective on the early development of 3D printing of DNA hydrogels is presented, and a potential implication of the hydrogel-based bone organoids built-up for bone regeneration is proposed.

Application of the "three-in-one" bone repair strategy in the treatment of osteoporotic fractures / 中华创伤杂志

Osteoporotic fractures secondary to osteoporosis increase very rapidly in incidence, and have become a major cause of disability and mortality in the elderly population. Currently, there have no standard guidelines for perioperative management, surgery and postoperative rehabilitation, causing multiple complications and poor therapeutic outcome. The authors previously proposed bone repair strategies including active anti-osteoporosis, adequate bone grafting and bone healing acceleration, namely "three-in-one" bone repair strategy. The care steps in osteoporotic fracture surgery inluded perioperative management, operative precaution, and postoperative prevention of secondary fractures. With this in mind, the authors further discussed the detailed application of "three-in-one" bone repair strategy including perioperative active anti-osteoporosis treatment, early rehabilitation training, standardized internal fixation selection, standard bone grafting methods and prevention of secondary complications, so as to promote the standardized treatment of osteoporotic fractures and improve the prognosis.

Guideline for the diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients (version 2023) / 中华创伤杂志

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly (version 2023) / 中华创伤杂志

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Efficacy of modified posterolateral approach combined with medial approach in open reduction and internal fixation of trimalleolar ankle fracture / 中华创伤杂志

Objective:To compare the clinical results of modified posterolateral approach combined medial approach versus traditional posterolateral approach combined with medial approach in open reduction and internal fixation of trimalleolar ankle fracture.Methods:A retrospective cohort study was used to analyze the clinical data of 46 patients with trimalleolar ankle fracture admitted to the First Affiliated Hospital of Naval Military Medical University from June 2013 to June 2019, including 14 males and 32 females, at age of 19-71 years [(49.2±14.9)years]. There were 33 patients with supination-external rotation type IV ankle fracture and 13 with pronation-external rotation type IV ankle fracture according to Lauge-Hansen classification. Open reduction and internal fixation was performed through the modified posterolateral approach combined with medial approach in 25 patients (modified approach group), and through the traditional posterolateral approach combined with medial approach in 21 patients (traditional approach group). The visual analogue score (VAS) at 3 days and 1 week after surgery, fracture healing time, range of ankle flexion and extension and Baird-Jackson score at the final follow-up and postoperative complications (numbness of the affect limb, wound necrosis, etc.) were compared between the two groups.Results:All patients were followed up for 11-21 months [(14.8±2.2)months]. There was no statistical difference in VAS or fracture healing time at 3 days after surgery between the two groups (all P>0.05). The VAS was 3.0 (3.0, 4.0)points in modified approach group at 1 week after surgery, significantly lower than 4.0 (3.0, 5.0)points in traditional approach group ( P<0.05). At the final follow-up, there was no statistical difference in range of ankle plantarflexion between the two groups ( P>0.05), but range of ankle dorsiflexion was significantly greater in modified approach group [(11.8±2.8)°] than that in traditional approach group [(8.1±3.5)°] ( P<0.01). At the final follow-up, Baird-Jackson score was not statistically different between the two groups ( P>0.05). There were 4 patients with numbness and 2 with wound necrosis in traditional approach group, but no numbness or wound necrosis occurred in modified approach group ( P<0.01). Conclusion:Both the modified posterolateral approach combined with medial approach and traditional posterolateral approach combined with medial approach can achieve good clinical results in open reduction and internal fixation of trimalleolar ankle fractures, but the former has advantages of better pain relief, better recovery of ankle dorsiflexion and less complications.

A new strategy for bone defect repair: bone organoids / 中华创伤杂志

Bone tissue repair has long been a hot topic and difficult issue in the field of regenerative medicine research. Although the rapid development of bone tissue engineering technology significantly accelerates the level of bone repair in recent years, bone regeneration research still faces many challenges such as difficulty in regeneration under pathological condition and unclear regenerative regulatory mechanisms. As a result, the evelopment of bone tissue engineering technology encounters a bottleneck, restricting more researches over bone regeneration and repair. As a novel concept, bone organoids are proposed and constructed in vitro with the help of tissue engineering technology based on biological theory, and can simulate the complex biological functions of bone in vivo. Bone organoids show broad application prospects in the research of bone regeneration, including elucidating regulatory regeneration mechanisms, screening biomaterials and promoting regeneration, etc. In this study, the authors preliminarily discuss the features, construction and value of bone organoids so as to provide new insight for the treatment of bone defect.

Expert consensus on diagnosis, prevention and treatment of perioperative lower extremity vein thrombosis in orthopedic trauma patients (2022 edition) / 中华创伤杂志

Lower extremity deep vein thrombosis (DVT) is one of the main complications in patients with traumatic fractures, and for severe patients, the DVT can even affect arterial blood supply, resulting in insufficient limb blood supply. If the thrombus breaks off, pulmonary embolism may occur, with a high mortality. The treatment and rehabilitation strategies of thrombosis in patients with lower extremity fractures have its particularity. DVT in traumatic fractures patients has attracted extensive attention and been largely studied, and the measures for prevention and treatment of DVT are constantly developing. In recent years, a series of thrombosis prevention and treatment guidelines have been updated at home and abroad, but there are still many doubts about the prevention and treatment of DVT in patients with different traumatic fractures. Accordingly, on the basis of summarizing the latest evidence-based medical evidence at home and abroad and the clinical experience of the majority of experts, the authors summarize the clinical treatment and prevention protocols for DVT in patients with traumatic fractures, and make this consensus on the examination and assessment, treatment, prevention and preventive measures for DVT in patients with different fractures so as to provide a practicable approach suitable for China ′s national conditions and improve the prognosis and the life quality of patients.

Betaine Attenuates Osteoarthritis by Inhibiting Osteoclastogenesis and Angiogenesis in Subchondral Bone.

Osteoarthritis (OA) is the most common type of arthritis with no effective therapy. Subchondral bone and overlying articular cartilage are closely associated and function as "osteo-chondral unit" in the joint. Abnormal mechanical load leads to activated osteoclast activity and increased bone resorption in the subchondral bone, which is implicated in the onset of OA pathogenesis. Thus, inhibiting subchondral bone osteoclast activation could prevent OA onset. Betaine, isolated from the Lycii Radicis Cortex (LRC), has been demonstrated to exert anti-inflammatory, antifibrotic and antiangiogenic properties. Here, we evaluated the effects of betaine on anterior cruciate ligament transection (ACLT)-induced OA mice. We observed that betaine decreased the number of matrix metalloproteinase 13 (MMP-13)-positive and collagen X (Col X)-positive cells, prevented articular cartilage proteoglycan loss and lowered the OARSI score. Betaine decreased the thickness of calcified cartilage and increased the expression level of lubricin. Moreover, betaine normalized uncoupled subchondral bone remodeling as defined by lowered trabecular pattern factor (Tb.pf) and increased subchondral bone plate thickness (SBP). Additionally, aberrant angiogenesis in subchondral bone was blunted by betaine treatment. Mechanistically, we demonstrated that betaine suppressed osteoclastogenesis in vitro by inhibiting reactive oxygen species (ROS) production and subsequent mitogen-activated protein kinase (MAPK) signaling. These data demonstrated that betaine attenuated OA progression by inhibiting hyperactivated osteoclastogenesis and maintaining microarchitecture in subchondral bone.

Corrigendum: A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5.

[This corrects the article DOI: 10.3389/fphar.2018.00022.].

Pay attention to role of bone marrow adipose tissue in the regulation of osteoporotic fracture healing / 中华创伤杂志

The osteoporotic fracture is characterized by a high disability rate，poor internal fixation strength，delayed bone healing，etc.，which greatly affects elderly health，so accelerating fracture healing is the key point of therapeutic strategies. Current researches mainly concentrate in bone formation acceleration and resorption inhibition，but the outcomes turn out to be unsatisfactory under the coupling of osteoblasts and osteoclasts. The accumulation of yellow adipose tissue in the medullary cavity is often arisen in patients with osteoporotic fractures，but its role and mechanism in bone metabolism remain unclear. Bone marrow adipocytes are differentiated from mesenchymal stromal cells and possess unique metabolic and secretory functions involving in energy metabolism，maintenance of hematopoietic microenvironment and regulation of bone metabolism balance. However，the role of bone marrow adipose tissue（BMAT）in osteoporotic fracture healing requires more elucidation. In this study，the authors discuss the key role and molecular mechanism of BMAT in the regulation of bone metabolism and homeostasis，aiming to provid new ideas and targets for the promotion of osteoporotic fracture healing.

Effect and mechanism of bone microenvironment on healing of osteoporotic fractures / 中华创伤杂志

The osteoporotic fracture is characterized by difficult treatment and poor prognosis. The studies of bone biology show that bone microenvironment changes during osteoporotic fractures，such as changes in immune factors，abnormal chemotaxis and differentiation of mesenchymal stem cells（MSCs），decreased estrogen secretion and receptor down-regulation and decreased mechanical sensitivity，which affect the fracture healing process. Current studies have shown that by improving the phenotypic polarization of macrophages，enhancing the chemotactic osteogenic activity of MSCs，supplementing estrogen and improving the biomechanical properties of bone can remodel the balance of bone microenvironment，thereby effectively improve the bone quality. The authors explore the effect and mechanism of bone microenvironment on healing of osteoporotic fractures from the perspectives of changes in bone microenvironment and imbalance of bone microenvironment that affect fracture healing and methods of bone microenvironment reconstruction，so as to provide new ideas for clinical treatment of osteoporotic fractures.

Challenges and potential solutions in treatment of osteoporotic fracture in China / 中华创伤杂志

The osteoporotic fracture, also known as fragility fracture, occurs due to osteoporosis. With the acceleration of aging in China, the incidence of osteoporotic fracture increases rapidly, which causes significant changes in the spectrum of orthopedic trauma. The osteoporotic fracture has both the commonness and particularity of fracture, which poses challenges to orthopedic surgeons. Meanwhile, the fast improvement of interdisciplinary research and the advancement of basic research in bone metabolism have brought many opportunities to facilitate the treatment of osteoporotic fracture. The authors intend to illustrate the challenges and solutions during the treatment of osteoporotic fracture by elaborating the awareness, fracture assessment, drug development, implant design, postoperative rehabilitation and refracture prevention to establish an improved protocol for the therapy.

Diagnosis and treatment misunderstandings and "three in one" bone repair strategies in osteoporotic fractures / 中华创伤杂志

Osteoporotic fractures have become major social problems threatening the health of the elderly population in China. Compared with conventional fractures, low bone mass, bone defect and retarded healing issues of osteoporotic fractures contribute to the difficulty in treatment and rehabilitation. Addressing major concerns in clinical settings, the "three in one" bone repair strategy focuses on anti-osteoporosis therapies, appropriate bone graft and fracture healing promotion. The authors summarize misunderstandings in diagnosis and treatment of osteoporotic fractures and repair strategies, expecting to improve prognosis and clinically standardize the treatments for osteoporotic fractures, to further improve therapeutic effect and living quality of the patients.

Research progress in effect of alendronate on healing of osteoporotic fracture / 中华创伤杂志

Fracture healing is a complex physiological process involving osteoblasts, osteoclasts and other cells and molecules. Typical fracture healing can be divided into four stages: inflammatory response, soft callus formation, hard callus formation, and bone remodeling. Osteoclasts play a leading role in hard callus formation and bone remodeling. Alendronate can inhibit osteoclast activity and bone loss in patients with osteoporosis, but it may also inhibit fracture healing. Therefore, whether alendronate can be used after osteoporotic fracture is controversial. In recent years, it has been found that alendronate can not affect the fracture healing, but also reduce the risk of secondary fracture and improve the prognosis of patients. In this article, the mechanism of alendronate and its effect on osteoporotic fracture healing by systemic and local use are reviewed, which can provide a reference for clinical selection of therapeutic drugs.

Efficacy of open reduction and internal fixation in management of senile osteoporotic ankle fractures / 中华创伤杂志

Objective@#To explore the efficacy of open reduction and internal fixation in the treatment of senile osteoporotic ankle fractures.@*Methods@#A retrospective case series study was conducted to analyze the data of 26 elderly patients with osteoporotic ankle fractures which all caused by sprain from June 2012 to June 2018 in Changhai Hospital, including 10 male and 16 female patients aged from 60 to 93 years (mean, 69.72 years). In these 26 patients, three had medial malleolus fractures, four had lateral malleolus fractures, six had double ankle fractures and 13 had cotton's fractures. According to the Lauge-Hansen type, all 26 patients can be classified into four types: 5 with supination external rotation type, 4 supination adduction type, 16 with pronation-external rotation type and 1 with pronation abduction type. All the patients received open reduction and internal fixation. Plate fixation was used for lateral and posterior malleolus fractures, plate fixation and cannulated screws were applied to fix the comminuted posterior malleolus fracture while in the comminuted internal malleolus fracture, the steel plate was used only when needed. Early professional functional rehabilitation training and active anti-osteoporosis treatment were applied. All the operation time and bleeding volume were recorded, and the reduction of fracture plus the healing of wounds were observed. At last follow-up, American Orthopedic Foot & Ankle Society (AOFAS) Ankle Hindfoot Scale was used to evaluate the treatment effect and the Visual Analogue Scale (VAS)to evaluate the therapeutic effect and the subjective satisfaction of the patients. Complications were recorded as well.@*Results@#All patients were followed up for 12-48 months (mean, 23.6 months). Operation time ranged from 30 to 95 minutes (mean, 70 minutes) and bleeding volume ranged from 10 to 150 ml (mean, 70 ml). All patients got satisfied reduction of fracture within 25 patients' incision healing in first intention, although one has fat liquefaction. AOFAS Ankle Hindfoot Scale improved from preoperative (84.4±10.8)points to (31.9±11.4)points at last follow-up (P<0.01), and the results were excellent in five patients, good in 17, fair in three and poor in one, with the excellent and good rate of 85%. VAS improved from preoperative(1.85±0.73)points to (9.23±0.28)points at last follow-up (P<0.01). Among 26 patients, 5 with ankle stiffness of different degree recovered after rehabilitation care, and 2 with internal malleolus fractures had bone displacement when receiving rehabilitation care, with no side effect on basic function. No serious complications such as wound infection or skin necrosis were found.@*Conclusion@#For osteoporotic ankle fractures in the elderly, open reduction and internal fixation can promote functional recovery and relieve pain.

Attach great importance to postoperative use of bisphosphonate following osteoporotic fracture / 中华创伤杂志

Osteoporotic fracture is a clinical problem resulting in significant morbidity and mortality. The main treatment for osteoporosis is bisphosphonate therapy. Bisphosphonates can inhibit the bone resorption by osteoclasts, inhibit bone alteration, and maintain bone mass. In recent years, basic and clinical studies have not found evidence that the use of bisphosphonates for the inhibition of fracture healing. Therefore, for the patients with confirmed osteoporotic fracture, bisphosphonate should be used to reduce the risk of re-fracture. The authors summarize the related studies in the bisphosphonate intervention for osteoporotic fracture and recommend postoperative use of bisphosphonate for osteoporotic fracture.

Controversies and countermeasures in treatment of osteoporotic distal humerus fracture in the elderly / 中华创伤杂志

The incidence of osteoporotic distal humeral fracture in the elderly is progressing in recent decade. Difficulty of reduction and poor internal fixation stability make osteoporotic distal humerus fractures become a challenging fracture type. Therefore, it is necessary to develop an individualized treatment plan based on the patient's condition and functional requirements. The authors discuss key questions in the treatment of osteoporotic distal humerus fracture in combination with current literatures and researches, so as to provide a reference for clinical diagnosis and treatment.

Focal issues in and strategies for treatment of periarticular osteoporotic fractures / 中华创伤杂志

Due to the aging population in China, the occurrence of osteoporotic fractures is surging. Osteoporotic fractures around the joints like wrist, hip or knee are usually more sophisticated, compared with those in vertebrae, causing more challenges in treatment and rehabilitation. When dealing with these cases, orthopedic surgeons should pay attention to systematic anti-osteoporosis therapy including medications like calcium supplement and bone metabolic regulation drugs. In addition, the bone quality of the patients and the implant stability should be considered during surgical procedures. Besides, the patients need to be guided to participate in early motions and weight-bearing exercises to gain better function and satisfactory recovery. The authors focus on the issues and strategies of anti-osteoporosis management, surgery protocol, early rehabilitation as well as long-term follow-up and prevention of the patients with periarticular osteoporotic fractures so as to provide references for clinical practices.