Gut microbiota alterations in postmenopausal women with osteoporosis and osteopenia from Shanghai, China.

Background: The importance of the gut microbiota in maintaining bone homeostasis has been increasingly emphasized by recent research. This study aimed to identify whether and how the gut microbiome of postmenopausal women with osteoporosis and osteopenia may differ from that of healthy individuals. Methods: Fecal samples were collected from 27 individuals with osteoporosis (OP), 44 individuals with osteopenia (ON), and 23 normal controls (NC). The composition of the gut microbial community was analyzed by 16S rRNA gene sequencing. Results: No significant difference was found in the microbial composition between the three groups according to alpha and beta diversity. At the phylum level, Proteobacteria and Fusobacteriota were significantly higher and Synergistota was significantly lower in the ON group than in the NC group. At the genus level, Roseburia, Clostridia_UCG.014, Agathobacter, Dialister and Lactobacillus differed between the OP and NC groups as well as between the ON and NC groups (p < 0.05). Linear discriminant effect size (LEfSe) analysis results showed that one phylum community and eighteen genus communities were enriched in the NC, ON and OP groups, respectively. Spearman correlation analysis showed that the abundance of the Dialister genus was positively correlated with BMD and T score at the lumbar spine (p < 0.05). Functional predictions revealed that pathways relevant to amino acid biosynthesis, vitamin biosynthesis, and nucleotide metabolism were enriched in the NC group. On the other hand, pathways relevant to metabolites degradation and carbohydrate metabolism were mainly enriched in the ON and OP groups respectively. Conclusions: Our findings provide new epidemiologic evidence regarding the relationship between the gut microbiota and postmenopausal bone loss, laying a foundation for further exploration of therapeutic targets for the prevention and treatment of postmenopausal osteoporosis (PMO).

Nanoengineered 3D-printing scaffolds prepared by metal-coordination self-assembly for hyperthermia-catalytic osteosarcoma therapy and bone regeneration.

The integration of functional nanomaterials with tissue engineering scaffolds has emerged as a promising solution for simultaneously treating malignant bone tumors and repairing resected bone defects. However, achieving a uniform bioactive interface on 3D-printing polymer scaffolds with minimized microstructural heterogeneity remains a challenge. In this study, we report a facile metal-coordination self-assembly strategy for the surface engineering of 3D-printed polycaprolactone (PCL) scaffolds with nanostructured two-dimensional conjugated metal-organic frameworks (cMOFs) consisting of Cu ions and 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP). A tunable thickness of Cu-HHTP cMOF on PCL scaffolds was achieved via the alternative deposition of metal ions and HHTP. The resulting composite PCL@Cu-HHTP scaffolds not only demonstrated potent photothermal conversion capability for efficient OS ablation but also promoted the bone repair process by virtue of their cell-friendly hydrophilic interfaces. Therefore, the cMOF-engineered dual-functional 3D-printing scaffolds show promising potential for treating bone tumors by offering sequential anti-tumor effects and bone regeneration capabilities. This work also presents a new avenue for the interface engineering of bioactive scaffolds to meet multifaceted demands in osteosarcoma-related bone defects.

Injectable hydrogels for bone regeneration with tunable degradability via peptide chirality modification.

The degradability of hydrogels plays a pivotal role in bone regeneration, yet its precise effects on the bone repair process remain poorly understood. Traditional studies have been limited by the use of hydrogels with insufficient variation in degradation properties for thorough comparative analysis. Addressing this gap, our study introduces the development of matrix metalloproteinase (MMP)-responsive hydrogels engineered with a tunable degradation rate, specifically designed for bone regeneration applications. These innovative hydrogels are synthesized by integrating MMP-sensitive peptides, which exhibit chirality-transferred amino acids, with norbornene (NB)-modified 8-arm polyethylene glycol (PEG) macromers to form the hydrogel network. The degradation behavior of these hydrogels is manipulated through the chirality of the incorporated peptides, resulting in the classification into L, LD, and D hydrogels. Remarkably, the L hydrogel variant shows a significantly enhanced degradation rate, both in vitro and in vivo, which in turn fosters bone regeneration by promoting cell migration and upregulating osteogenic gene expression. This research highlights the fundamental role of hydrogel degradability in bone repair and lays the groundwork for the advancement of degradable hydrogel technologies for bone regeneration, offering new insights and potential for future biomaterials development.

A novel approach for anterior cruciate ligament tibial avulsion fracture: arthroscopic modified suture bridge fixation technique.

INTRODUCTION: Anterior cruciate ligament (ACL) tibial avulsion fracture is a rare injury, which usually happens in adults with traffic accidents or sports injuries. Surgery interventions are common treatment methods, they can restore knee function and help to return to normal life. In this study, we described an arthroscopic modified suture bridge fixation technique for ACL tibial avulsion fractures and explored the feasibility and therapeutic effects. MATERIALS AND METHODS: This retrospective study reviewed data from January 2020 to May 2022. Data were collected on 18 patients (10 males and 8 females) with ACL tibial avulsion fractures and underwent arthroscopic modified suture bridge fixation technique. The study analyzed surgical data about intraoperative blood loss, operation time, hospital stay, fracture healing time, and visual analog scale (VAS). Functional evaluation of the knee joint was performed using the anterior drawer test, Lysholm knee scoring scale, International Knee Documentation Committee (IKDC), and knee range of motion (ROM). RESULTS: All 18 patients were followed up between 12 and 20 months, with an average of 15.22 ± 1.96 months. The intraoperative blood loss was approximately 15-40 mL, averaging 25.78 ± 6.19 mL. The operation time was 65-85 min, with a mean of 74.89 ± 4.86 min. The hospital stay of patients was 3-5 days, with a mean of 3.89 ± 0.76 days. The mean fracture healing time was 8-12 weeks after surgery, with a mean of 9.22 ± 1.7 weeks. All incisions healed grade I without infection. There were no internal fixation failures, neurovascular injuries, and lower extremity deep venous thrombosis. The anterior drawer test was negative in all patients. At the final follow-up, the mean VAS score was 0-3, averaging 1.56 ± 0.71. The Lysholm score of the injured knee was 89-96, with an average of 92.50 ± 2.50; the IKDC score was 88-93, with an average of 90.44 ± 1.89; the knee ROM was 110-126°, with an average of 120.67° ± 4.31°. CONCLUSION: Results demonstrated that the modified suture bridge fixation technique under arthroscope could provide reliable fixation and favorable clinical effects for ACL tibial avulsion fractures. This is a simple, minimally invasive, effective, and clinically applicable surgical method for ACL tibial avulsion fracture.

MMP13-targeted siRNA-loaded micelles for diagnosis and treatment of posttraumatic osteoarthritis.

Posttraumatic osteoarthritis (PTOA) patients are often diagnosed by X-ray imaging at a middle-late stage when drug interventions are less effective. Early PTOA is characterized by overexpressed matrix metalloprotease 13 (MMP13). Herein, we constructed an integrated diagnosis and treatment micelle modified with MMP13 enzyme-detachable, cyanine 5 (Cy5)-containing PEG, black hole quencher-3 (BHQ3), and cRGD ligands and loaded with siRNA silencing MMP13 (siM13), namely ERMs@siM13. ERMs@siM13 could be cleaved by MMP13 in the diseased cartilage tissues to detach the PEG shell, causing cRGD exposure. Accordingly, the ligand exposure promoted micelle uptake by the diseased chondrocytes by binding to cell surface αvß3 integrin, increasing intracellular siM13 delivery for on-demand MMP13 downregulation. Meanwhile, the Cy5 fluorescence was restored by detaching from the BHQ3-containing micelle, precisely reflecting the diseased cartilage state. In particular, the intensity of Cy5 fluorescence generated by ERMs@siM13 that hinged on the MMP13 levels could reflect the PTOA severity, enabling the physicians to adjust the therapeutic regimen. Finally, in the murine PTOA model, ERMs@siM13 could diagnose the early-stage PTOA, perform timely interventions, and monitor the OA progression level during treatment through a real-time detection of MMP13. Therefore, ERMs@siM13 represents an appealing approach for early-stage PTOA theranostics.

Expert consensus on Prospective Precision Diagnosis and Treatment Strategies for Osteoporotic Fractures.

Osteoporotic fractures are the most severe complications of osteoporosis, characterized by poor bone quality, difficult realignment and fixation, slow fracture healing, and a high risk of recurrence. Clinically managing these fractures is relatively challenging, and in the context of rapid aging, they pose significant social hazards. The rapid advancement of disciplines such as biophysics and biochemistry brings new opportunities for future medical diagnosis and treatment. However, there has been limited attention to precision diagnosis and treatment strategies for osteoporotic fractures both domestically and internationally. In response to this, the Chinese Medical Association Orthopaedic Branch Youth Osteoporosis Group, Chinese Geriatrics Society Geriatric Orthopaedics Committee, Chinese Medical Doctor Association Orthopaedic Physicians Branch Youth Committee Osteoporosis Group, and Shanghai Association of Integrated Traditional Chinese and Western Medicine Osteoporosis Professional Committee have collaborated to develop this consensus. It aims to elucidate emerging technologies that may play a pivotal role in both diagnosis and treatment, advocating for clinicians to embrace interdisciplinary approaches and incorporate these new technologies into their practice. Ultimately, the goal is to improve the prognosis and quality of life for elderly patients with osteoporotic fractures.

A new method of anterior talofibular ligament reconstruction: Arthroscopically artificial ligament reconstruction with tensional remnant-repair.

PURPOSE: To investigate the clinical effects of arthroscopically artificial ligament reconstruction with tensional remnant-repair in patients who are obese, and/or with demand for highly intensive sports, and/or with poor-quality ligament remnants. METHODS: A retrospective case series study was performed on patients treated by arthroscopically anterior talofibular ligament (ATFL) reconstruction with tensional remnant repair technique from January 2019 to August 2021. General data, including demographics, surgical time, and postoperative adverse events, were recorded. The American Orthopaedic Foot and Ankle Society score (AOFAS), foot and ankle ability measure (FAAM), visual analog scale (VAS), and anterior talar translation were measured preoperatively and at 6 weeks, 3 months, and 2 years postoperatively. Ultrasonography examination was performed preoperatively and 2 years postoperatively to evaluate the ATFL. Data were analyzed using SPSS 19.0. F test was used to analyze the pre- and postoperative VAS, FAAM, and AOFAS scores. The significance was set at p < 0.05. RESULTS: There were 20 males and 10 females among the patients with a mean age of (30.71 ± 5.81) years. The average surgical time was (40.21 ± 8.59) min. No adverse events were observed after surgery. At 2 years postoperatively, the anterior talar translation test showed grade 0 laxity in all patients. VAS score significantly decreased from preoperatively to 6 weeks, 3 months, and 2 years postoperatively (p < 0.001). Improvement of FAAM score and the AOFAS score from preoperatively to 6 weeks, 3 months, and 2 years postoperatively was statistically significant (p < 0.001). At 3 months postoperatively, most patients (23/30) could return to their pre-injured activities of daily living status. At 2 years postoperatively, all patients were able to return to their pre-injured activities of daily living status, and almost every patient (18/19) who expected highly intensive sports returned to sports with only 1 obese patient failing to achieve the goal. The ultrasonography examination at 2 years postoperatively showed that there was a linear band structure of soft tissue on the tension-rich fiber tape image from the fibular to the talar attachment sits of ATFL. CONCLUSION: The novel arthroscopically artificial ligament reconstruction with tensional remnant-repair technique for ATFL achieved satisfactory clinical outcomes in the short and medium term after operation, and allowed early return to pre-injured activities, which could be a reliable option for patients with chronic lateral ankle instability.

A study of fracture lines distribution characteristics in complete articular fractures of the patella.

Objective: The objective of this study was to unveil the characteristics of fracture lines distribution and explore its clinical significance of complete articular fractures of the patella. Methods: A consecutive series of image data from 88 patients with complete articular patella fractures were retrospectively included. Three-dimensional reconstruction images of the patella fractures were created and collected. Subsequently, these reconstructed images were visually overlaid onto a standard anterior and posterior patella template. The fracture lines were then identified, traced onto the template, and utilized to generate patella fracture maps. Furthermore, the incidence rate of patella fracture lines involving the distal pole was analyzed. Results: The maps depict the fracture lines of complete articular patella fractures. For simple and complex patella fractures, the primary fracture lines primarily converge within the Middle and Lower regions, exhibiting a transverse pattern. Conversely, the primary fracture lines in comminuted patella fractures are randomly dispersed across the patella. Examining the maps, approximately 63.6% (56/88) of complete articular patella fractures exhibited involvement of the distal pole in the anterior view, while 48.9% (43/88) displayed distal pole fractures in the posterior view. The incidence of distal pole injury increased progressively with the severity of patella fractures. Conclusion: The patterns and distribution of fracture lines in cases of complete articular patella fractures are prominently illustrated on the constructed fracture maps. Familiarity with these common characteristics of complete articular patella fracture, especially with the distal pole injury, can aid surgeons in developing preoperative planning, executing surgical strategies effectively, and reducing inappropriate treatment.

Harnessing Nucleic Acids Nanotechnology for Bone/Cartilage Regeneration.

The effective regeneration of weight-bearing bone defects and critical-sized cartilage defects remains a significant clinical challenge. Traditional treatments such as autologous and allograft bone grafting have not been successful in achieving the desired outcomes, necessitating the need for innovative therapeutic approaches. Nucleic acids have attracted significant attention due to their ability to be designed to form discrete structures and programmed to perform specific functions at the nanoscale. The advantages of nucleic acid nanotechnology offer numerous opportunities for in-cell and in vivo applications, and hold great promise for advancing the field of biomaterials. In this review, the current abilities of nucleic acid nanotechnology to be applied in bone and cartilage regeneration are summarized and insights into the challenges and future directions for the development of this technology are provided.

Bone/cartilage organoid on-chip: Construction strategy and application.

The necessity of disease models for bone/cartilage related disorders is well-recognized, but the barrier between ex-vivo cell culture, animal models and the real human body has been pending for decades. The organoid-on-a-chip technique showed opportunity to revolutionize basic research and drug screening for diseases like osteoporosis and arthritis. The bone/cartilage organoid on-chip (BCoC) system is a novel platform of multi-tissue which faithfully emulate the essential elements, biologic functions and pathophysiological response under real circumstances. In this review, we propose the concept of BCoC platform, summarize the basic modules and current efforts to orchestrate them on a single microfluidic system. Current disease models, unsolved problems and future challenging are also discussed, the aim should be a deeper understanding of diseases, and ultimate realization of generic ex-vivo tools for further therapeutic strategies of pathological conditions.

Expert consensus on the bone repair strategy for osteoporotic fractures in China.

Osteoporotic fractures, also known as fragility fractures, are prevalent in the elderly and bring tremendous social burdens. Poor bone quality, weak repair capacity, instability, and high failure rate of internal fixation are main characteristics of osteoporotic fractures. Osteoporotic bone defects are common and need to be repaired by appropriate materials. Proximal humerus, distal radius, tibia plateau, calcaneus, and spine are common osteoporotic fractures with bone defect. Here, the consensus from the Osteoporosis Group of Chinese Orthopaedic Association concentrates on the epidemiology, characters, and management strategies of common osteoporotic fractures with bone defect to standardize clinical practice in bone repair of osteoporotic fractures.

Loss of Bcl-3 delays bone fracture healing through activating NF-κB signaling in mesenchymal stem cells.

Background: Bone fracture healing is a postnatal regenerative process in which fibrocartilaginous callus formation and bony callus formation are important. Bony callus formation requires osteoblastic differentiation of MSCs. Materials and methods: The formation of callus was assessed by µCT, Safranin-O, H&E and Masson trichrome staining. Osteogenesis of MSCs was analyzed by ALP staining, ARS staining, qRT-PCR and WB. And we also used IF and TOP/FOP Flash luciferase reporter to assess the nuclear translocation of PP65. Results: In this study, we found Bcl-3 showed a significant correlation with bone fracture healing. Results of µCT showed that loss of Bcl-3 delays bone fracture healing. Safranin-O, H&E and Masson trichrome staining confirmed that loss of Bcl-3 impacted the formation of cartilage and woven bone in callus. Further experiments in vitro manifested that Bcl-3-knockdown could inhibit MSCs osteoblastic differentiation through releasing the inhibition on NF-κB signaling by Co-IP, IF staining and luciferase reporter assay. Conclusions: We unveiled that loss of Bcl-3 could lead to inhibited osteogenic differentiation of MSCs via promoting PP65 nuclear translocation. The translational potential of this article: Our data demonstrated that overexpression of Bcl-3 accelerates bone fracture healing, which serves as a promising therapeutic target for bone fracture treatment.

Engineered Cell Membrane-Derived Nanocarriers: The Enhanced Delivery System for Therapeutic Applications.

There has been a rapid development of biomimetic platforms using cell membranes as nanocarriers to camouflage nanoparticles for enhancing bio-interfacial capabilities. Various sources of cell membranes have been explored for natural functions such as circulation and targeting effect. Biomedical applications of cell membranes-based delivery systems are expanding from cancer to multiple diseases. However, the natural properties of cell membranes are still far from achieving desired functions and effects as a nanocarrier platform for various diseases. To obtain multi-functionality and multitasking in complex biological systems, various functionalized modifications of cell membranes are being developed based on physical, chemical, and biological methods. Notably, many research opportunities have been initiated at the interface of multi-technologies and cell membranes, opening a promising frontier in therapeutic applications. Herein, the current exploration of natural cell membrane functionality, the design principles for engineered cell membrane-based delivery systems, and the disease applications are reviewed, with a special focus on the emerging strategies in engineering approaches.

[Morphological analysis of coronal femoral intertrochanteric fracture and its effect on reduction and internal fixation].

OBJECTIVE: To investigate the morphology of coronal femoral intertrochanteric fracture and its effect on reduction and internal fixation. METHODS: The clinical and imaging data of 46 patients with femoral intertrochanteric fracture who met the selection criteria between August 2017 and October 2018 were reviewed. There were 15 males and 31 females; the age ranged from 62 to 91 years, with an average of 72.8 years. The causes of injury included walking falls in 35 cases, falling out of bed in 4 cases, and traffic accidents in 7 cases. The AO/Orthopaedic Trauma Association classification was type 31-A1 in 11 cases and type 31-A2 in 35 cases. All patients underwent closed reduction and internal fixation with intramedullary nails. During the operation, fracture reduction and fixation were performed according to the preoperative evaluation results. According to the patients' preoperative X-ray film and CT three-dimensional reconstruction images, the direction of the coronal fracture line of the femoral intertrochanter and the morphological characteristics of the fracture block were observed; and the coronal fracture discrimination analysis was carried out for the fractures of different AO/OTA types. The percentages of coronal femoral intertrochanteric fractures diagnosed by preoperative X-ray film and CT three-dimensional reconstruction were calculated and statistically analyzed. The fracture reduction, the position of internal fixation [measurement of tip-apex distance (TAD)]. and the reliability of internal fixation were observed after operation. RESULTS: X-ray film was not easy to identify coronary fracture, and the coronal fracture line and the shape of the fracture piece weree clearly visible in CT three-dimensional reconstruction images. The morphological characteristics of the coronary fracture block: in AO/OTA 31-A1 type, the fracture line extended obliquely backward from the anterior tip of the large rotor, above the small rotor with or without small rotor fracture; in AO/OTA 31-A2 type, fracture line extended obliquely backward from the anterior tip of the large rotor to below the small rotor. Thirteen cases (28.3%) of coronal fractures were found on preoperative X-ray films, and 35 cases (76.1%) were found by CT three-dimensional reconstruction, showing significant difference ( χ 2=21.083, P=0.000). In AO/OTA 31-A1 type patients, the proportion of coronal fractures found by X-ray film and CT three-dimensional reconstruction was 18.2% (2/11) and 54.5% (6/11), respectively, and that in AO/OTA 31-A2 type patients was 31.4% (11/35) and 82.9% (29/35), respectively, showing significant differences ( χ 2=3.143, P=0.000; χ 2=20.902, P=0.000). Among the 35 patients with coronal fractures, 6 cases (17.1%) of AO/OTA 31-A1 type, 29 cases (82.9%) of AO/OTA 31-A2 type. The operation time of the patient was 80-112 minutes, with an average of 95 minutes; the intraoperative blood loss was 180-450 mL, with an average of 360 mL. There was no complication such as infection, falling pneumonia, and deep vein thrombosis of the lower extremities. At 3 days after operation, the internal fixators were all in the proper position. The TAD was 0.9-1.8 cm, with an average of 1.4 cm. All patients were followed up 14-18 months, with an average of 16 months. All the fractures healed osseously, and there was no complication such as nonunion and loosening of internal fixation. CONCLUSION: CT three-dimensional reconstruction can better identify coronal femoral intertrochanteric fractures than X-ray films, and accurately recognize and analyze the incidence and morphological characteristics of coronal fractures, which can help formulate more effective surgical strategies to promote patient recovery.

RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss.

Receptor activator of NF-κB ligand (RANKL) is essential for osteoclast formation and bone remodeling. Nevertheless, the cellular source of RANKL for osteoclastogenesis has not been fully uncovered. Different from peripheral adipose tissue, bone marrow (BM) adipose lineage cells originate from bone marrow mesenchymal stromal cells (BMSCs). Here, we demonstrate that adiponectin promoter-driven Cre expression (AdipoqCre ) can target bone marrow adipose lineage cells. We cross the AdipoqCre mice with ranklfl/fl mice to conditionally delete RANKL from BM adipose lineage cells. Conditional deletion of RANKL increases cancellous bone mass of long bones in mice by reducing the formation of trabecular osteoclasts and inhibiting bone resorption but does not affect cortical bone thickness or resorption of calcified cartilage. AdipoqCre ; ranklfl/fl mice exhibit resistance to estrogen deficiency and rosiglitazone (ROS)-induced trabecular bone loss but show bone loss induced by unloading. BM adipose lineage cells therefore represent an essential source of RANKL for the formation of trabecula osteoclasts and resorption of cancellous bone during remodeling under physiological and pathological conditions. Targeting bone marrow adiposity is a promising way of preventing pathological bone loss.

Intramedullary nails in combination with reconstruction plate in the treatment of unstable intertrochanteric femoral fractures with lateral wall damage.

BACKGROUND: The unstable intertrochanteric femur fracture remains a challenge for surgeons. However, few studies have compared the clinical effectiveness of intramedullary nail in combination with a reconstruction plate and intramedullary nail alone in the treatment of patients with unstable intertrochanteric femoral fractures with lateral wall damage. METHODS: This study retrospectively analyzed 16 patients with 31 A3 intertrochanteric fractures treated with the intramedullary nail in combination with reconstruction plate (the study group) and 19 patients with 31 A3 intertrochanteric fractures treated with intramedullary nail alone (the control group) between January 2012 and January 2018. The operation time, intra-operative blood loss, time of fracture healing, and complication rates of post-operative fixation failure were assessed between the two groups. At the follow-up of post-operative six and 12 months, Harris hip score (HHS) and the Parker-Palmer mobility score (PPMS) were used to evaluate the functional states and mobility levels. RESULTS: The distribution of all basic characteristics was similar between the two groups (P ˃ 0.05). The study group had longer operation time and more intra-operative blood loss in comparison with the control group (P < 0.001), while the study group had shorter fracture healing time (P = 0.03) and lower fixation failure rate as compared with the control group. Regarding the functional outcome, the study group had higher HHSs and PPMS than the control group (P = 0.003). CONCLUSIONS: Although intramedullary nails in combination with reconstruction plates had longer operation time and more intra-operative blood loss, it might be superior to intramedullary nail alone in terms of fracture healing time, fixation failure complication rate, and post-operative functional recovery.

Tailored Mesoporous Inorganic Biomaterials: Assembly, Functionalization, and Drug Delivery Engineering.

Infectious or immune diseases have caused serious threat to human health due to their complexity and specificity, and emerging drug delivery systems (DDSs) have evolved into the most promising therapeutic strategy for drug-targeted therapy. Various mesoporous biomaterials are exploited and applied as efficient nanocarriers to loading drugs by virtue of their large surface area, high porosity, and prominent biocompatibility. Nanosized mesoporous nanocarriers show great potential in biomedical research, and it has become the research hotspot in the interdisciplinary field. Herein, recent progress and assembly mechanisms on mesoporous inorganic biomaterials (e.g., silica, carbon, metal oxide) are summarized systematically, and typical functionalization methods (i.e., hybridization, polymerization, and doping) for nanocarriers are also discussed in depth. Particularly, structure-activity relationship and the effect of physicochemical parameters of mesoporous biomaterials, including morphologies (e.g., hollow, core-shell), pore textures (e.g., pore size, pore volume), and surface features (e.g., roughness and hydrophilic/hydrophobic) in DDS application are overviewed and elucidated in detail. As one of the important development directions, advanced stimuli-responsive DDSs (e.g., pH, temperature, redox, ultrasound, light, magnetic field) are highlighted. Finally, the prospect of mesoporous biomaterials in disease therapeutics is stated, and it will open a new spring for the development of mesoporous nanocarriers.

Comparison between osteosynthesis with interlocking nail and minimally invasive plating for proximal- and middle-thirds of humeral shaft fractures.

PURPOSE: Options for the treatment of proximal- and middle-thirds of humeral shaft fractures include intramedullary interlocking nail (IMN) and minimally invasive plate osteosynthesis (MIPO). However, whether IMN provides better clinical outcomes than MIPO surgical technique still remains unclear. This study was designed to compare clinical outcomes of the IMN with MIPO technique for the treatment of proximal- and middle-thirds of humeral shaft fractures. METHOD: A retrospective cohort analysis of 55 proximal- and middle-thirds of humeral shaft fractures surgically treated using IMN (n = 25) or MIPO (n = 30) from January 2012 to January 2016. Peri-operative and follow-up data (a minimum of 1 year) of the patients (aged from 18 to 56 years) were collected. Operative time, union time, VAS scores, surgery-related complications, and implant removal rate were compared between the two groups in this study. Besides, the functional outcomes were evaluated using the Rating Scale of American Shoulder and Elbow Surgeons' Form (ASES) and Mayo Elbow Performance Score System (MEPS). RESULT: We found significantly shorter operative time and much less blood loss in IMN group, and lower VAS scores in the IMN group after surgery at first and third months but not at the sixth month. Complication rate was found to be relatively higher in the MIPO group when compared to the IMN group. No significant difference was observed between these two groups regarding ASES and MEPS scores. Three patients in the MIPO group suffered iatrogenic radial nerve injury and recovered after four to five months later. No implant failures occurred in either group. CONCLUSION: Intramedullary interlocking nail seemed to be superior to minimally invasive plate osteosynthesis in the treatment of proximal- and middle-thirds of humeral shaft fractures due to shorter operative time and union time, less early post-operative pain, and fewer complications. The intramedullary interlocking nail could be considered a better surgical option for the management of proximal middle humeral fractures, though it may also depend on the surgeons' skills and learning curve. Further in-depth prospective studies are in great need to verify our conclusion.