Mechanisms of the Masquelet technique to promote bone defect repair and its influencing factors.

The Masquelet technique, also known as the induced membrane technique, is a surgical technique for repairing large bone defects based on the use of a membrane generated by a foreign body reaction for bone grafting. This technique is not only simple to perform, with few complications and quick recovery, but also has excellent clinical results. To better understand the mechanisms by which this technique promotes bone defect repair and the factors that require special attention in practice, we examined and summarized the relevant research advances in this technique by searching, reading, and analysing the literature. Literature show that the Masquelet technique may promote the repair of bone defects through the physical septum and molecular barrier, vascular network, enrichment of mesenchymal stem cells, and high expression of bone-related growth factors, and the repair process is affected by the properties of spacers, the timing of bone graft, mechanical environment, intramembrane filling materials, artificial membrane, and pharmaceutical/biological agents/physical stimulation.

Multifunctional Carbon Dots for Biomedical Applications: Diagnosis, Therapy, and Theranostic.

Designing suitable nanomaterials is an ideal strategy to enable early diagnosis and effective treatment of diseases. Carbon dots (CDs) are luminescent carbonaceous nanoparticles that have attracted considerable attention. Through facile synthesis, they process properties including tunable light emission, low toxicity, and light energy transformation, leading to diverse applications as optically functional materials in biomedical fields. Recently, their potentials have been further explored, such as enzyme-like activity and ability to promote osteogenic differentiation. Through refined synthesizing strategies carbon dots, a rich treasure trove for new discoveries, stand a chance to guide significant development in biomedical applications. In this review, the authors start with a brief introduction to CDs. By presenting mechanisms and examples, the authors focus on how they can be used in diagnosing and treating diseases, including bioimaging failure of tissues and cells, biosensing various pathogenic factors and biomarkers, tissue defect repair, anti-inflammation, antibacterial and antiviral, and novel oncology treatment. The introduction of the application of integrated diagnosis and treatment follows closely behind. Furthermore, the challenges and future directions of CDs are discussed. The authors hope this review will provide critical perspectives to inspire new discoveries on CDs and prompt their advances in biomedical applications.

CCL25 Inhibition Alleviates Sepsis-Induced Acute Lung Injury and Inflammation.

Purpose: Acute lung injury (ALI) is a common clinical syndrome with high mortality. The chemokine ligand 25 (CCL25) is involved in inflammation, leukocyte trafficking and immunoregulation. However, the role and mechanism of CCL25 in ALI are not fully understood yet. The aim of this study was to explore the relationship between acute lung injury and CCL25. Patients and Methods: In this study, we first examined chemokine expression in sepsis patients and found that serum CCL25 expression levels were relatively high in sepsis patients compared to healthy individuals. Based on this, we designed in vitro and in vivo experiments to verify the validity of the theory. In vitro, we used lipopolysaccharide-stimulated human pulmonary microvascular endothelial cells (HPMECs). In vivo, we established male C57BL/6 mice cecal ligation puncture (CLP) model of sepsis. Results: In vitro, we used lipopolysaccharide-stimulated human pulmonary microvascular endothelial cells (HPMECs) and found significantly higher expression of CCL25 by enzyme-linked immunosorbent assay. Inhibition of CCL25 resulted in a significant decrease in the expression of inflammatory cytokines in HPMECs. In addition, we found that CCL25 promoted increased endothelial permeability by reducing the expression of tight junction proteins and was associated with activation of the P38 MAPK pathway by measuring the transepithelial electrical resistance and fluorescence intensity of fluorescein isothiocyanate. Results from luciferase assays and chromatin immunoprecipitation assays showed that inhibition of NF-κB activity in HPMECs decreased CCL25 expression, but addition of recombinant CCL25 increased cell permeability and inflammatory cytokine expression. In vivo, we established male C57BL/6 mice cecal ligation puncture (CLP) model of sepsis. We found that inhibition of CCL25 significantly reduced inflammatory cytokine expression in a CLP-induced sepsis model, thereby alleviating lung tissue damage in mice. Conclusion: Our study suggests that CCL25 contributed to the development of ALI by modulating the functions of microvascular endothelial cells.

[A case-control study of two internal fixation methods in the treatment of comminuted fracture of inferior pole of patella].

OBJECTIVE: To compare the effects of tension band combined with patellar cerclage and memory alloy patellar concentrator fixation in the treatment of comminuted fracture of the lower pole of patella. METHODS: From July 2015 to July 2019, 60 patients with distal patellar fracture were treated and were divided into two groups according to different operation methods. In group A, 30 patients were fixed with memory alloy patellar concentrator (NiTi PC), 17 males and 13 females, aged 20 to 71 (39.4±9.9) years, including 19 cases of falling injury, 9 cases of traffic injury and 2 cases of sports injury. The time from injury to operation was 10 to 75 (33.1±7.8) hours; 30 cases in group B were fixed with tension band andcerclage, 15 males and 15 females, aged 21 to 76 (38.6±10.2) years, including 17 cases of falling injury, 12 cases of traffic injury and 1 case of smashing injury. The time from injury to operation was 10 to 91 (34.5±9.1) hours. The curative effects of two groups were observed and compared. RESULTS: All 60 patients were followed up for 9 to 30 months. There was no significant difference in intraoperative bleeding, operation time, follow-up time and fracture healing time between the two groups. Six months after operation, according to the Bostman function score of knee joint:30 cases in group A, the total score was 28.6±4.7, of which 26 cases were excellent and 4 cases were good. The total score of 30 cases in group B was 25.5±4.4, of which 20 cases were excellent, 8 cases were good and 2 cases were poor. There were significant differences in Bostman total score and curative effect evaluation between two groups (P<0.05). The score of group A was significantly better than that of group B. In group B, 1 case had Kirschner wire withdrawal, 2 cases had joint stiffness and 3 cases had internal fixation irritation. CONCLUSION: Memory alloy patellar concentrator is strong and reliable in the treatment of inferior patellar fracture. It can take early rehabilitation exercise after operation, with good recovery of joint function and range of motion and less complications.

Comparing the performance of tourniquet application between self-aid and buddy-aid: in ordinary and simulated scenarios.

OBJECTIVES: Combat Application Tourniquet (CAT) is generally applied by self-aid or buddy-aid for exsanguinating extremity hemorrhage. The purpose of this study was to compare the accuracy, time and effectiveness between self-aid and buddy aid in ordinary and simulated scenarios. METHODS: A total of 64 undergraduates from the Red Cross Commando of a military medical university participated in this study, which involved ordinary and simulated scenarios. In each scenario, every participant completed tourniquet application to upper and lower extremities by self-aid and buddy-aid, respectively. Measures of time, accuracy and effectiveness were assessed by an examiner identically after each application. RESULTS: Compared with the performance of CAT application by buddy-aid, the time of application to upper extremities by self-aid increased by 8.39 s (P<0.001) and 3.24 s to lower extremities (P<0.05), and the percentage of pulse elimination by self-aid declined by 13.29% and 10.93% to both upper and lower extremities, respectively (P<0.05). Simulated combat performance showed longer time and lower accuracy (P<0.05). CONCLUSIONS: The hypothesized different performances between self-aid and buddy-aid, as well as between ordinary and simulated scenarios were verified in this study, indicating the need for superior tourniquet design for self-aid and rigorous deployment readiness training, especially for self-aid in tourniquet application.

Umbilical Mesenchymal Stem Cell-Derived Exosome-Encapsulated Hydrogels Accelerate Bone Repair by Enhancing Angiogenesis.

Repair of large bone defects represents a major challenge for orthopedic surgeons. The newly formed microvessels inside grafts play a crucial role in successful bone tissue engineering. Previously, an active role for mesenchymal stem cell (MSC)-derived exosomes in blood vessel development and progression was suggested in the repair of multiple tissues. However, the reports on the application of MSC-derived exosomes in the repair of large bone defects are sparse. In this study, we encapsulated umbilical MSC-derived exosomes (uMSCEXOs) in hyaluronic acid hydrogel (HA-Gel) and combined them with customized nanohydroxyapatite/poly-ε-caprolactone (nHP) scaffolds to repair cranial defects in rats. Imaging and histological evaluation indicated that the uMSCEXOs/Gel/nHP composites markedly enhanced bone regeneration in vivo, and the uMSCEXOs might play a key role in this process. Moreover, the in vitro results demonstrated that uMSCEXOs promoted the proliferation, migration, and angiogenic differentiation of endothelial progenitor cells (EPCs) but did not significantly affect the osteogenic differentiation of BMSCs. Importantly, mechanistic studies revealed that exosomal miR-21 was the potential intercellular messenger that promoted angiogenesis by upregulating the NOTCH1/DLL4 pathway. In conclusion, our findings exhibit a promising exosome-based strategy in repairing large bone defects through enhanced angiogenesis, which potentially regulated by the miR-21/NOTCH1/DLL4 signaling axis.

A new technology using a customized 3D printed fixator to assist fracture reduction and fixation: Technical note.

BACKGROUND: Poor reduction can lead to complications such as deformity and delayed fracture healing. We introduce a 3D printed external fixator technology that can assist in fracture reduction and fixation. METHODS: A fractured long bone was first fixed by a temporary external fixator and then scanned with computed tomography. Three-dimensional reconstruction of the contour and bone fragments of the affected limb was performed using Mimics software, and the fracture reduction was simulated. Subsequently, data were imported into SolidWorks software for customized external fixator design and 3D printing. Through the precise assembly of the 3D printed external fixator and external fixation pins, automatic fracture reduction. RESULTS: The patient's fractures were well reduced, firmly fixed, and the postoperative fractures healed well with no complications. CONCLUSION: The technique we introduce not only assists in fracture reduction for temporary external fixation but can also be used as a definitive treatment for long bone fractures.

Investigation of Mg-xLi-Zn alloys for potential application of biodegradable bone implant materials.

Implant therapy after osteosarcoma surgery is a major clinical challenge currently, especially the requirements for mechanical properties, degradability of the implants, and their inhibition of residual tumor cells. Biodegradable magnesium (Mg) alloy as medical bone implant material has full advantages and huge potential development space. Wherein, Mg-lithium (Li) based alloy, as an ultra-light alloy, has good properties for implants under certain conditions, and both Mg and Li have inhibitory effects on tumor cells. Therefore, Mg-Li alloy is expected to be applied in bone implant materials for mechanical supporting and inhibiting tumor cells simultaneously. In this contribution, the Mg-xLi-Zinc (Zn) series alloys (x = 3 wt%, 6 wt%, 9 wt%) were prepared to study the influence of different elements and contents on the structure and properties of the alloy, and the biosafety of the alloy was also evaluated. Our data showed that the yield strength, tensile strength, and elongation of as-cast Mg-xLi-Zn alloy were higher than those of as-cast Mg-Zn alloy; Mg-xLi-Zn alloy can kill osteosarcoma cells (MG-63) in a concentration-dependent manner, wherein Mg-3Li-Zn alloy (x = 3 wt%) and Mg-6Li-Zn alloy (x = 6 wt%) promoted the proliferation of osteoblasts (MC3T3) at a certain concentration of Li. In summary, our study demonstrated that the Mg-6Li-Zn alloy could be potentially applied as a material of orthopedic implant for its excellent multi-functions.

Research progress of heat stroke during 1989-2019: a bibliometric analysis.

BACKGROUND: Heat stroke (HS) is an acute physical disorder that is associated with a high risk of organ dysfunction and even death. HS patients are usually treated symptomatically and conservatively; however, there remains a lack of specific and effective drugs in clinical practice. An analysis of publication contributions from institutions, journals and authors in different countries/regions was used to study research progress and trends regarding HS. METHODS: We extracted all relevant publications on HS between 1989 and 2019 from Web of Science. Using the Statistical Package for Social Science (SPSS, version 24) and the software GraphPad Prism 8, graphs were generated and statistical analyses were performed, while VOSviewer software was employed to visualize the research trends in HS from the perspectives of co-occurring keywords. RESULTS: As of April 14, 2020, we identified 1443 publications with a citation frequency of 5216. The United States accounted for the largest number of publications (36.2%) and the highest number of citations (14,410), as well as the highest H-index at 74. Although the sum of publications from China ranked second, there was a contradiction between the quantity and quality of publications. Furthermore, Medicine & Science in Sports & Exercise published the most papers related to HS, with Lin MT publishing the most papers in this field (112), while the review by Knochel JP received the highest citation frequency at 969. The keyword heat-stress appeared most recently, with an average appearing year of 2015.5. In the clinical research cluster, exertional heat-stroke was determined to be the hotspot, while ambient-temperature and heat waves were the new trends in the epidemiological research cluster. CONCLUSIONS: Corresponding to this important field, while the contributions of the publications from the United States were significant, the mismatch between the quantity and quality of publications from China must be examined. Moreover, it is hypothesized that clinical and epidemiological studies may become hotspots in the near future.

Calcium silicate bioactive ceramics induce osteogenesis through oncostatin M.

Immune reactions are a key factor in determining the destiny of bone substitute materials after implantation. Macrophages, the most vital factor in the immune response affecting implants, are critical in bone formation, as well as bone biomaterial-mediated bone repair. Therefore, it is critical to design materials with osteoimmunomodulatory properties to reduce host-to-material inflammatory responses by inducing macrophage polarization. Our previous study showed that calcium silicate (CS) bioceramics could significantly promote osteogenesis. Herein, we further investigated the effects of CS on the behavior of macrophages and how macrophages regulated osteogenesis. Under CS extract stimulation, the macrophage phenotype was converted to the M2 extreme. Stimulation by a macrophage-conditioned medium that was pretreated by CS extracts resulted in a significant enhancement of osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), indicating the important role of macrophage polarization in biomaterial-induced osteogenesis. Mechanistically, oncostatin M (OSM) in the macrophage-conditioned medium promoted osteogenic differentiation of BMSCs through the ERK1/2 and JAK3 pathways. This in vivo study further demonstrated that CS bioceramics could stimulate osteogenesis better than ß-TCP implants by accelerating new bone formation at defective sites in the femur. These findings improve our understanding of immune modulation of CS bioactive ceramics and facilitate strategies to improve the in vitro osteogenesis capability of bone substitute materials.

Comparison of the Kirschner Wire Tension Band with a Novel Nickel-Titanium Arched Shape-Memory Alloy Connector in Transverse Patellar Fractures: A Retrospective Study.

This study aims to compare the clinical outcomes of the nickel-titanium arched shape-memory alloy connector (hereafter referred to as the ASC) and tension band fixation for the treatment of transverse patellar fractures. We retrospectively analyzed a total of 257 patients with transverse patellar fractures who were treated at our emergency orthopaedics department from March 2010 to March 2017. Either an ASC or the Kirschner wire (K-wire) tension band had been used to treat these fractures according to surgeons' experience and preference. We compared operative details, postoperative recovery, and postoperative knee function at 6 months. In terms of surgical duration, blood loss, incision length, length of hospital stay, and postoperative complications, patients in the ASC group showed significantly better results than patients in the K-wire group (p < 0.05). There were no significant differences between the two groups in terms of fracture healing time, knee mobility, and the Boström score at the postoperative 6-month evaluation (p > 0.05). Though, there were similar functional outcomes between two groups whose transverse patellar fractures were different methods, we found that the ASC method was a more reliable, more minimally invasive, and safer treatment option than the tension band wiring method using K-wires, resulting in less tissue damage, shorter surgical duration, shorter length of hospital stay, and fewer complications.

Mapping Thematic Trends and Analysing Hotspots Concerning the Use of Stem Cells for Cartilage Regeneration: A Bibliometric Analysis From 2010 to 2020.

Background: Defects of articular cartilage represent a common condition that usually progresses to osteoarthritis with pain and dysfunction of the joint. Current treatment strategies have yielded limited success in these patients. Stem cells are emerging as a promising option for cartilage regeneration. We aim to summarize the developmental history of stem cells for cartilage regeneration and to analyse the relevant trends and hotspots. Methods: We screened all relevant literature on stem cells for cartilage regeneration from Web of Science during 2010-2020 and analysed the research trends in this field by VOSviewer and CiteSpace. We also summarized previous clinical trials. Results: We screened 1,011 publications. China contributed the largest number of publications (317, 31.36%) and citations (81,376, 48.61%). The United States achieved the highest H-index (39). Shanghai Jiao Tong University had the largest number of publications (34) among all full-time institutions. The Journal of Biomaterials and Stem Cell Research and Therapy published the largest number of studies on stem cells for cartilage regeneration (35). SEKIYA I and YANG F published the majority of articles in this field (14), while TOH WS was cited most frequently (740). Regarding clinical research on stem cells for cartilage regeneration, the keyword "double-blind" emerged in recent years, with an average year of 2018.75. In tissue engineering, the keyword "3D printing" appeared latest, with an average year of 2019.625. In biological studies, the key word "extracellular vesicles" appeared latest, with an average year of 2018.9091. The current research trend indicates that basic research is gradually transforming to tissue engineering. Clinical trials have confirmed the safety and feasibility of stem cells for cartilage regeneration. Conclusion: Multiple scientific methods were employed to reveal productivity, collaborations, and research hotspots related to the use of stem cells for cartilage regeneration. 3D printing, extracellular vesicles, and double-blind clinical trials are research hotspots and are likely to be promising in the near future. Further studies are needed for to improve our understanding of this field, and clinical trials with larger sample sizes and longer follow-up periods are needed for clinical transformation.

Application of a novel shape-memory alloy concentrator in displaced olecranon fractures: a report of the technique and mid-term clinical results.

PURPOSE: Olecranon fracture is a common upper limb fracture, and several surgical approaches have been advocated for its fixation. To overcome the complications associated with common techniques, we present a novel shape-memory alloy concentrator, an alternative for tension band compression, to fix olecranon fracture. METHODS: Fifty-seven patients (26 men and 31 women) with olecranon fracture, with a mean age of 45 years, were included in this study. Each patient had undergone open reduction and internal fixation using the Nitinol (Ni-Ti) arched shape-memory connector (ASC). The clinical assessments were performed using the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire and the Mayo Elbow Performance (MEP) score, which were both recorded at the final follow-up visit. RESULTS: The patients were followed up for 44 months on average (range, 31 to 56 months). No patients were lost to follow-up, and all of the olecranon fractures healed in an average of 15 weeks (range, 10 to 34 weeks). The mean DASH score was 8.6 (range, 0 to 32.4), and the mean MEP score was 92.5 (range, 74 to 100). Nine patients showed postoperative complications: prominent hardware (2), infection (1), loss of the range of functional motion (5), and heterotopic ossification (1). CONCLUSION: The ASC may serve as a favorable device for multi-fragmented and comminuted fractures with rare hardware irritation and may also provide continuous concentrative compression to accelerate osseous healing, thereby aiding the restoration and permitting an early rehabilitation with a low incidence of postoperative complications.

Development of a light field measuring system with corrected distortion based on imaging analysis.

A light field microscope can realize three-dimensional measurement through only one exposure by the addition of a critical optical component called a microlens array (MLA). MLA errors will introduce aberrations in the captured image and then affect measurement results. This paper proposes a light field measuring system with aberration correction based on imaging analysis. The effect of MLA errors is investigated and quantitatively analyzed through a series of simulation studies. Aberration correction is realized based on computational imaging, in which an image segmentation and fusion distortion model is employed to correct the distortion, while a gradient-based linear recognition algorithm is used to address MLA rotation errors. Experimental results show that the developed light field measuring system can achieve improved measurement accuracy by correcting aberrations with the proposed algorithms.

Theoretical and Experimental Studies of the Functional Structure Effect on Directional Transport in Biomicrofluidics.

Surfaces in nature that are capable of directional transport of liquids by using their own microstructures have become a research focus in recent years. However, research on the directional transport function of biomicrostructures is still ongoing, and there is still a lack of quantitative studies on the functions of such biostructures so far. Based on the microstructural surface of Nepenthes, a systematic research study on the biomimetic microstructure surface is presented. In this study, the mechanism of the directional transport function is analyzed, and the functional structure effect on directional transport is investigated in detail. The realization of the transport function of the Nepenthes peristome is achieved by the unique surface microstructure and super-hydrophilic surface. The structures are modeled with simplified geometries, and the critical geometric parameters affecting the transportation function are identified. To verify the transportation function of the designed microstructure, orthogonal experiments are designed to explore the relationship between the liquid transport and the structural parameters. Experimental studies show that the transport speed of the liquid varies while the transportation function is achieved with the modeled structures. The velocity increases as the distance within the two microcavities increases and decreases as the width of the microcavity increases. The study is helpful for better understanding the mechanism of directional transportation by microstructures and provides optimum guidance for producing functional structures applied in biomicrofluidics.

Silver-decorated mesostructured cellular silica foams as excellent antibacterial hemostatic agents for rapid and effective treatment of hemorrhage.

Uncontrolled bleeding, such as deep, narrow or irregular wound hemorrhage, has been a major cause of death in peacetime and wartime. Besides, traditional hemostatic agents are lack of antibacterial properties, which could not provide effective protection on open wound. In this paper, a novel antibacterial hemostatic agent composed of mesostructured cellular silica foams (MCF) decorated with silver ions (MCF-Ag) was synthesized by hydrothermal method. Hemorrhage wound infected with Escherichia coli was applied to evaluate its antibacterial and hemostatic performance both in vitro and in vivo. Both MCF and MCF-Ag showed excellent hemostasis in vitro and in vivo. The MCF-Ag demonstrated significant antibacterial effect. By contrast, no obvious antibacterial effect was observed from the MCF. The above results demonstrate that the MCF-Ag is an excellent antibacterial hemostatic agent with splendid water absorption and antibacterial capacity.

Combination of mini locking plate and nitinol arched shape-memory connector for purely lateral malleolus fractures: technique and clinical results.

BACKGROUND: Lateral malleolus fractures occur frequently. The common techniques for fixing purely lateral malleolus fractures are often challenging, owing to the extent of soft tissue damage and fracture non-union. Herein, we report a new treatment that entails minimally invasive insertion and continuous compression of the broken ends as a novel technique, and evaluate its clinical results. METHODS: This study enrolled 21 patients (13 males and 8 females; mean age 32.06±3.45 years, range 23-69 years) with purely lateral malleolus fractures. Each patient underwent open reduction treatment with a mini locking plate for internal fixation and compression of the fracture end with an Arched Shape-Memory Connector (ASC). The clinical assessments were made using the American Orthopedic Foot and Ankle Society (AOFAS) scores, which were recorded at the final follow-up visit. RESULTS: The patients were followed for an average of 14.7±1.2 months (range, 12-18 months). None of the patients showed surgical failure, and all of the purely lateral malleolus fractures healed in an average of 12.6±1.5 weeks (range, 10-16 weeks). The mean AOFAS score was 88.94 (range, 83-90). CONCLUSIONS: The new treatment had beneficial outcomes for purely lateral malleolus fractures. Mini locking plates are minimally invasive for surgical intervention, and combined with continuous concentrated compression with an ASC to accelerate osseous healing, they aid in restoration of function and enable early rehabilitation with a low incidence of postoperative complications.