Biomechanical Microenvironment Research Articles

Pulling the Rug Out from Under: Biomechanical Microenvironment Remodeling for Induction of Hepatic Stellate Cell Quiescence.

Hepatic fibrosis progresses concomitantly with a variety of biomechanical alternations, especially increased liver stiffness. These biomechanical alterations have long been considered as pathological consequences. Recently, growing evidence proposes that these alternations result in the fibrotic biomechanical microenvironment, which drives the activation of hepatic stellate cells (HSCs). Here, an inorganic ascorbic acid-oxidase (AAO) mimicking nanozyme loaded with liquiritigenin (LQ) is developed to trigger remodeling of the fibrotic biomechanical microenvironment. The AAO mimicking nanozyme is able to consume intracellular ascorbic acid, thereby impeding collagen I deposition by reducing its availability. Simultaneously, LQ inhibits the transcription of lysyl oxidase like 2 (LOXL2), thus impeding collagen I crosslinking. Through its synergistic activities, the prepared nanosystem efficiently restores the fibrotic biomechanical microenvironment to a near-normal physiological condition, promoting the quiescence of HSCs and regression of fibrosis. This strategy of remodeling the fibrotic biomechanical microenvironment, akin to "pulling the rug out from under", effectively treats hepatic fibrosis in mice, thereby highlighting the importance of tissue biomechanics and providing a potential approach to improve hepatic fibrosis treatment.

Research advances in mechanistic signaling in pulmonary fibrosis

Pulmonary fibrosis is a complex and intractable disease characterized by extracellular matrix accumulation and altered mechanical properties of lung tissue. Biomechanical properties are closely related to the development, progression, and treatment of tissue fibrosis. In this review, we summarized the changes in the pulmonary biomechanical microenvironment, highlight the role of mechanotransduction in pulmonary fibrosis, and describe recent clinical advances targeting mechanical signals to alleviate pulmonary fibrosis.

The Three-dimensional Environment of Type Ⅰ Collagen Gels With Varying Stiffness Modulates the Immunological Functions of NK Cells

To construct type Ⅰ collagen gels with different stiffness and to investigate the effects of three-dimensional (3D) culture environments of the gels on the morphology, free migration ability, and cell killing function of natural killer (NK) cells. Type Ⅰ collagen was isolated from the tails of Sprague Dawley (SD) rats and collagen gels with different levels of stiffnesses were prepared accordingly. The microstructure of the collagen gels was observed by laser confocal microscopy. The stiffness of the collagen gels was assessed by measuring the plateau modulus with a rheometer. NK-92MI cells were cultured in collagen gels with different levels of stiffness. The morphology of NK-92MI cells was observed by inverted microscope. High content imaging system was used to record the free migration process of NK-92MI cells and analyze the migration speed and distance. NK-92MI cells were cultured with type Ⅰ collagen gels with different levels of stiffness for 24 h and 48 h and, then, co-cultured with human colorectal DLD-1, a human adenocarcinoma epithelial cell line. CCK8 assay was performed to determine the proliferation rate of DLD-1 cells and analyze the cell killing ability of NK-92MI cells. Low-stiffness type Ⅰ collagen gel and high-stiffness type Ⅰ collagen gel with the respective stiffness of (10.970±2.10) Pa and (114.50±3.40) Pa were successfully prepared. Compared with those cultured with the low-stiffness type Ⅰ collagen gel, the NK-92MI cells in the high-stiffness type Ⅰ collagen gel showed a more elongated shape (P<0.05), the mean area of the cells was reduced ([69.88±26.97] μm2 vs. [46.59±21.62] μm2, P<0.05), the roundness of the cells decreased (0.82±0.12 vs. 0.78±0.18, P<0.05), cell migration speed decreased ([2.50±0.91] μm/min vs. [1.70±0.72] μm/min, P<0.001) and the migration distance was shortened ([147.10±53.74] μm vs. [98.03± 40.95] μm, P<0.0001), with all the differences being statistically significant. Compared with those cultured with the low-stiffness type Ⅰ collagen gel, NK-92MI cells cultured with high-stiffness type Ⅰ collagen gel for 24 h could promote DLD-1 cell proliferation, with the proliferation rate being (46.39±12.79)% vs. (65.87±4.45)% (P<0.05) and reduce the cell killing ability. Comparison of the cells cultured for 48 h led to similar results, with the proliferation rates being (31.36±2.88)% vs. (74.57±2.16)% (P<0.05), and the differences were all statistically significant. The 3D culture environment of type Ⅰ collagen gels with different levels of stiffness alters the morphology, migration ability, and killing function of NK-92MI cells. This study provides the research basis for exploring and understanding the mechanisms by which the biomechanical microenvironment affects the immune response of NK cells, as well as laying the theoretical foundation for optimizing immunotherapy protocols.

Challenges of aortic valve tissue culture – maintenance of viability and extracellular matrix in the pulsatile dynamic microphysiological system

BackgroundCalcific aortic valve disease (CAVD) causes an increasing health burden in the 21st century due to aging population. The complex pathophysiology remains to be understood to develop novel prevention and treatment strategies. Microphysiological systems (MPSs), also known as organ-on-chip or lab-on-a-chip systems, proved promising in bridging in vitro and in vivo approaches by applying integer AV tissue and modelling biomechanical microenvironment. This study introduces a novel MPS comprising different micropumps in conjunction with a tissue-incubation-chamber (TIC) for long-term porcine and human AV incubation (pAV, hAV).ResultsTissue cultures in two different MPS setups were compared and validated by a bimodal viability analysis and extracellular matrix transformation assessment. The MPS-TIC conjunction proved applicable for incubation periods of 14–26 days. An increased metabolic rate was detected for pulsatile dynamic MPS culture compared to static condition indicated by increased LDH intensity. ECM changes such as an increase of collagen fibre content in line with tissue contraction and mass reduction, also observed in early CAVD, were detected in MPS-TIC culture, as well as an increase of collagen fibre content. Glycosaminoglycans remained stable, no significant alterations of α-SMA or CD31 epitopes and no accumulation of calciumhydroxyapatite were observed after 14 days of incubation.ConclusionsThe presented ex vivo MPS allows long-term AV tissue incubation and will be adopted for future investigation of CAVD pathophysiology, also implementing human tissues. The bimodal viability assessment and ECM analyses approve reliability of ex vivo CAVD investigation and comparability of parallel tissue segments with different treatment strategies regarding the AV (patho)physiology.

Depth camera-based model for studying the effects of muscle loading on distal radius fracture healing

BackgroundDistal radius fractures (DRFs) treated with volar locking plates (VLPs) allows early rehabilitation exercises favourable to fracture recovery. However, the role of rehabilitation exercises induced muscle forces on the biomechanical microenvironment at the fracture site remains to be fully explored. The purpose of this study is to investigate the effects of muscle forces on DRF healing by developing a depth camera-based fracture healing model. MethodFirst, the rehabilitation-related hand motions were captured by a depth camera system. A macro-musculoskeletal model is then developed to analyse the data captured by the system for estimating hand muscle and joint reaction forces which are used as inputs for our previously developed DRF model to predict the tissue differentiation patterns at the fracture site. Finally, the effect of different wrist motions (e.g., from 60° of extension to 60° of flexion) on the DRF healing outcomes will be studied. ResultsMuscle and joint reaction forces in hands which are highly dependent on hand motions could significantly affect DRF healing through imposed compressive and bending forces at the fracture site. There is an optimal range of wrist motion (i.e., between 40° of extension and 40° of flexion) which could promote mechanical stimuli governed healing while mitigating the risk of bony non-union due to excessive movement at the fracture site. ConclusionThe developed depth camera-based fracture healing model can accurately predict the influence of muscle loading induced by rehabilitation exercises in distal radius fracture healing outcomes. The outcomes from this study could potentially assist osteopathic surgeons in designing effective post-operative rehabilitation strategies for DRF patients.

Engineered biomechanical microenvironment of articular chondrocytes based on heterogeneous GelMA hydrogel composites and dynamic mechanical compression

Tissue-engineered articular cartilage constructs are currently not able to equal native tissues in terms of mechanical and biological properties. A major cause lies in the deficiency in engineering the biomechanical microenvironment (BMME) of articular chondrocytes. In this work, to engineer the BMME of articular chondrocytes, heterogeneous hydrogel structures of gelatin methacrylated (GelMA) containing differential-stiffness domains were first fabricated, and then periodic dynamic mechanical stimulations were applied to the hydrogel structures. The chondrocyte phenotype of ATDC5 cells was enhanced as the spatial differentiation in stiffness was increased in the hydrogel structures and was further strengthened by dynamic mechanical stimulation. It was speculated that the mechanical signals generated by the engineered BMME were sensed by the cells through the integrin β1-FAK signaling pathway. This study revealed the key role of the combined effects of differential and dynamic BMME on the chondrocyte phenotype, which could provide theoretical guidance for highly active tissue-engineered articular cartilage.

Combining biomechanical stimulation and chronobiology: a novel approach for augmented chondrogenesis?

The unique structure and composition of articular cartilage is critical for its physiological function. However, this architecture may get disrupted by degeneration or trauma. Due to the low intrinsic regeneration properties of the tissue, the healing response is generally poor. Low-grade inflammation in patients with osteoarthritis advances cartilage degradation, resulting in pain, immobility, and reduced quality of life. Generating neocartilage using advanced tissue engineering approaches may address these limitations. The biocompatible microenvironment that is suitable for cartilage regeneration may not only rely on cells and scaffolds, but also on the spatial and temporal features of biomechanics. Cell-autonomous biological clocks that generate circadian rhythms in chondrocytes are generally accepted to be indispensable for normal cartilage homeostasis. While the molecular details of the circadian clockwork are increasingly well understood at the cellular level, the mechanisms that enable clock entrainment by biomechanical signals, which are highly relevant in cartilage, are still largely unknown. This narrative review outlines the role of the biomechanical microenvironment to advance cartilage tissue engineering via entraining the molecular circadian clockwork, and highlights how application of this concept may enhance the development and successful translation of biomechanically relevant tissue engineering interventions.

Development of a novel air–liquid interface airway tissue equivalent model for in vitro respiratory modeling studies

The human airways are complex structures with important interactions between cells, extracellular matrix (ECM) proteins and the biomechanical microenvironment. A robust, well-differentiated in vitro culture system that accurately models these interactions would provide a useful tool for studying normal and pathological airway biology. Here, we report the development and characterization of a physiologically relevant air–liquid interface (ALI) 3D airway ‘organ tissue equivalent’ (OTE) model with three novel features: native pulmonary fibroblasts, solubilized lung ECM, and hydrogel substrate with tunable stiffness and porosity. We demonstrate the versatility of the OTE model by evaluating the impact of these features on human bronchial epithelial (HBE) cell phenotype. Variations of this model were analyzed during 28 days of ALI culture by evaluating epithelial confluence, trans-epithelial electrical resistance, and epithelial phenotype via multispectral immuno-histochemistry and next-generation sequencing. Cultures that included both solubilized lung ECM and native pulmonary fibroblasts within the hydrogel substrate formed well-differentiated ALI cultures that maintained a barrier function and expressed mature epithelial markers relating to goblet, club, and ciliated cells. Modulation of hydrogel stiffness did not negatively impact HBE differentiation and could be a valuable variable to alter epithelial phenotype. This study highlights the feasibility and versatility of a 3D airway OTE model to model the multiple components of the human airway 3D microenvironment.

Extracellular matrix: A regenerative conduit in dentistry

Periodontal disease causes tooth loss by destroying the attachment system and tooth supporting tissues. Periodontal therapy seeks to not only halt the advancement of periodontal disease, but also to repair lost structures caused by disease progression. Extracellular matrix (ECM) is a complex three-dimensional network made up of an array of multidomain macromolecules organised in a cell/tissue-specific manner that serves as a structural scaffold in the formation of supramolecular assemblies in tissue architecture that regulate cell growth and differentiation, thereby providing a suitable biochemical and biomechanical microenvironment for regeneration of lost tissue structures. This article's goal is to provide a simplified and concise understanding of the structure and components of ECM, as well as to shed light on its utility as a regenerative conduit in the field of periodontal regeneration.

Anatomical Tissue Engineering of the Anterior Cruciate Ligament Entheses.

The firm integration of anterior cruciate ligament (ACL) grafts into bones remains the most demanding challenge in ACL reconstruction, since graft loosening means graft failure. For a functional-tissue-engineered ACL substitute to be realized in future, robust bone attachment sites (entheses) have to be re-established. The latter comprise four tissue compartments (ligament, non-calcified and calcified fibrocartilage, separated by the tidemark, bone) forming a histological and biomechanical gradient at the attachment interface between the ACL and bone. The ACL enthesis is surrounded by the synovium and exposed to the intra-articular micromilieu. This review will picture and explain the peculiarities of these synovioentheseal complexes at the femoral and tibial attachment sites based on published data. Using this, emerging tissue engineering (TE) strategies addressing them will be discussed. Several material composites (e.g., polycaprolactone and silk fibroin) and manufacturing techniques (e.g., three-dimensional-/bio-printing, electrospinning, braiding and embroidering) have been applied to create zonal cell carriers (bi- or triphasic scaffolds) mimicking the ACL enthesis tissue gradients with appropriate topological parameters for zones. Functionalized or bioactive materials (e.g., collagen, tricalcium phosphate, hydroxyapatite and bioactive glass (BG)) or growth factors (e.g., bone morphogenetic proteins [BMP]-2) have been integrated to achieve the zone-dependent differentiation of precursor cells. However, the ACL entheses comprise individual (loading history) asymmetric and polar histoarchitectures. They result from the unique biomechanical microenvironment of overlapping tensile, compressive and shear forces involved in enthesis formation, maturation and maintenance. This review should provide a road map of key parameters to be considered in future in ACL interface TE approaches.

Nicotinamide Mononucleotide Alleviates Angiotensin II-Induced Human Aortic Smooth Muscle Cell Senescence in a Microphysiological Model.

The occurrence and development of aortic aneurysms are accompanied by senescence of human aortic smooth muscle cells (HASMCs). Because the mechanism of HASMC senescence has not been fully elucidated, the efficacy of various antisenescence treatments varies. Decreased nicotinamide adenine dinucleotide (NAD + ) levels are one of the mechanisms of cell senescence, and there is a lack of evidence on whether increasing NAD + levels could alleviate HASMC senescence and further retard the progression of aortic aneurysms.We constructed an HASMC-based organ-on-a-chip microphysiological model. RNA sequencing was performed on cell samples from the vehicle control and angiotensin II groups to explore biological differences. We detected cellular senescence markers and NAD + levels in HASMC-based organ-on-a-chip. Subsequently, we pretreated HASMC using the synthetic precursor of NAD + , nicotinamide mononucleotide, and angiotensin II treatment, and used rhythmic stretching to investigate whether nicotinamide mononucleotide could delay HASMC senescence.The HASMC-based organ-on-a-chip model can simulate the biomechanical microenvironment of HASMCs in vivo, and the use of angiotensin II in the model replicated senescence in HASMCs. The senescence of HASMCs was accompanied by downregulation of the expression level of nicotinamide phosphoribosyltransferase and NAD + . Pretreatment with nicotinamide mononucleotide significantly increased the NAD + level and alleviated the senescence of HASMCs, but did not change the expression level of nicotinamide phosphoribosyltransferase.Our study provides a complementary research platform between traditional cell culture and animal experiments to explore HASMC senescence in aortic aneurysms. Furthermore, it provides evidence for NAD + boosting therapy in the clinical treatment of aortic aneurysms.

Improving the Biological Properties of UHMWPE Biocomposite for Orthopedic Applications.

Bone plates are essential for bone fracture healing because they modify the biomechanical microenvironment at the fracture site to provide the necessary mechanical fixation for fracture fragments. The objective of this study was to determine cell availability, antibacterial activity, and wettability through a contact angle test. However, biocomposites that involve UHMWPE reinforced with n-HA and n-TiO2 particles at different fractions (0, 1.5, 2.5, 3.5, and 4.5%) and 5% from carbon and Kevlar fibers were fabricated by hot pressing technique. In vitro studies revealed good cell viability on the surface of the hybrid biocomposite even after 72 hr. The UHMEPE nanocomposite reinforced with carbon showed better cell attachment for fibroblasts than other UHMWPE nanocomposite materials reinforced with Kevlar fiber. The results of the contact angle measurements indicated that the incorporation of nanoparticles and the fiber reinforcement increased the wettability due to the hydrophilic character of nanobiocomposite, and also (UHMWPE-4.5% wt. TiO2-CF) biocomposite was the best wettability (∼48% as compared to neat UHMWPE). Antibacterial experiments involving Gram-positive bacteria, Staphylococcus aureus, confirm excellent bactericidal property for (UHMWPE-4.5% wt. TiO2-CF) biocomposite. Thermal analysis of the produced nanocomposites revealed that they had higher melting and crystallinity temperatures than pure UHMWPE.

Investigation of Compression and Hardness for UHMWPE Bio-composites as Internal Bone Plate Fixation

Bone plates are essential for bone fracture healing because they modify the biomechanical microenvironment at the fracture site to provide the necessary mechanical fixation for fracture fragments. This paper addresses the use of composite bone plates in healing long-bone fractures such as transverse fractures of the femur. However, stress shielding in the bone due to metal plates can be reduced by designing implants with Bio-composites that involve Ultra high molecular polyethylene reinforced (UHMWPE) with Nano hydroxyapatite (n-HA) and Nano titanium dioxide (n-TiO2) particles at different weight fraction (0,1.5,2.5,3.5and 4. 5%) and 5% of carbon and Kevlar fibers. FRIT spectrum was used to identify the incorporation between the matrix and Nano particles, and the shifting in main peaks confirmed the good cross-linking within the composite structure. The specimens thus prepared were subjected to a compression test, hardness test, and density. The results indicated that UHMWPE+4.5%n-HA+CF hybrid biocomposite has the highest compressive strength and hardness properties. In contrast, UHMWPE+4.5%TiO2+CF has the highest density, which increased with increasing percentages of weight fraction of Nano-particles, where the compression strength 53 MPa, hardness property ranges 65.6 shore D, and density 1.09 (g/cm3). According to the current study's findings, it is possible to create bio-composites as internal fixation device with improved performance by placing different fiber reinforcements.

Immunomodulatory Blood-Derived Hybrid Hydrogels as Multichannel Microenvironment Modulators for Augmented Bone Regeneration.

Autologous blood-derived protein hydrogels have shown great promise in the field of personalized regenerative medicine. However, the inhospitable regenerative microenvironments, especially the unfavorable immune microenvironment, are closely associated with their limited tissue-healing outcomes. Herein, novel immunomodulatory blood-derived hybrid hydrogels (PnP-iPRF) are rationally designed and constructed for enhanced bone regeneration via multichannel regulation of the osteogenic microenvironment. Such double-network hybrid hydrogels are composed of clinically approved injectable platelet-rich fibrin (i-PRF) and polycaprolactone/hydroxyapatite composite nanofibers by using enriched polydopamine (PDA) as the anchor. The polycaprolactone component in PnP-iPRF provides a reinforced structure to stimulate osteoblast differentiation in a proper biomechanical microenvironment. Most importantly, the versatile PDA component in PnP-iPRF can not only offer high adhesion capacity to the growth factors of i-PRF and create a suitable biochemical microenvironment for sustained osteogenesis but also reprogram the osteoimmune microenvironment via the induction of M2 macrophage polarization to promote bone healing. The present study will provide a new paradigm to realize enhanced osteogenic efficacy by multichannel microenvironment regulations and give new insights into engineering high-efficacy i-PRF hydrogels for regenerative medicine.

A Novel Step-T-Junction Microchannel for the Cell Encapsulation in Monodisperse Alginate-Gelatin Microspheres of Varying Mechanical Properties at High Throughput.

Cell encapsulation has been widely employed in cell therapy, characterization, and analysis, as well as many other biomedical applications. While droplet-based microfluidic technology is advantageous in cell microencapsulation because of its modularity, controllability, mild conditions, and easy operation when compared to other state-of-art methods, it faces the dilemma between high throughput and monodispersity of generated cell-laden microdroplets. In addition, the lack of a biocompatible method of de-emulsification transferring cell-laden hydrogel from cytotoxic oil phase into cell culture medium also hurtles the practical application of microfluidic technology. Here, a novel step-T-junction microchannel was employed to encapsulate cells into monodisperse microspheres at the high-throughput jetting regime. An alginate–gelatin co-polymer system was employed to enable the microfluidic-based fabrication of cell-laden microgels with mild cross-linking conditions and great biocompatibility, notably for the process of de-emulsification. The mechanical properties of alginate-gelatin hydrogel, e.g., stiffness, stress–relaxation, and viscoelasticity, are fully adjustable in offering a 3D biomechanical microenvironment that is optimal for the specific encapsulated cell type. Finally, the encapsulation of HepG2 cells into monodisperse alginate–gelatin microgels with the novel microfluidic system and the subsequent cultivation proved the maintenance of the long-term viability, proliferation, and functionalities of encapsulated cells, indicating the promising potential of the as-designed system in tissue engineering and regenerative medicine.

Construction of a Human Aorta Smooth Muscle Cell Organ-On-A-Chip Model for Recapitulating Biomechanical Strain in the Aortic Wall.

Conventional two-dimensional cell culture techniques and animal models have been used in the study of human thoracic aortic aneurysm and dissection (TAAD). However, human TAAD sometimes cannot be characterized by animal models. There is an apparent species gap between clinical human studies and animal experiments that may hinder the discovery of therapeutic drugs. In contrast, the conventional cell culture model is unable to simulate in vivo biomechanical stimuli. To this end, microfabrication and microfluidic techniques have developed greatly in recent years, providing novel techniques for establishing organoids-on-a-chip models that replicate the biomechanical microenvironment. In this study, a human aorta smooth muscle cell organ-on-a-chip (HASMC-OOC) model was developed to simulate the pathophysiological parameters of aortic biomechanics, including the amplitude and frequency of cyclic strain experienced by human aortic smooth muscle cells (HASMCs) that play a vital role in TAAD. In this model, the morphology of HASMCs became elongated in shape, aligned perpendicularly to the strain direction, and presented a more contractile phenotype under strain conditions than under static conventional conditions. This was consistent with the cell orientation and phenotype in native human aortic walls. Additionally, using bicuspid aortic valve-related TAAD (BAV-TAAD) and tricuspid aortic valve-related TAAD (TAV-TAAD) patient-derived primary HASMCs, we established BAV-TAAD and TAV-TAAD disease models, which replicate HASMC characteristics in TAAD. The HASMC-OOC model provides a novel in vitro platform that is complementary to animal models for further exploring the pathogenesis of TAAD and discovering therapeutic targets.

Biomaterial–Related Cell Microenvironment in Tissue Engineering and Regenerative Medicine

An appropriate cell microenvironment is key to tissue engineering and regenerative medicine. Revealing the factors that influence the cell microenvironment is a fundamental research topic in the fields of cell biology, biomaterials, tissue engineering, and regenerative medicine. The cell microenvironment consists of not only its surrounding cells and soluble factors, but also its extracellular matrix (ECM) or nearby external biomaterials in tissue engineering and regeneration. This review focuses on six aspects of biomaterial–related cell microenvironments: ① chemical composition of materials, ② material dimensions and architecture, ③ material–controlled cell geometry, ④ effects of material charges on cells, ⑤ matrix stiffness and biomechanical microenvironment, and ⑥ surface modification of materials. The present challenges in tissue engineering are also mentioned, and eight perspectives are predicted.

Retrospective clinical outcomes in the definitive treatment of high-energy tibial diaphyseal fractures using hexapod external fixator versus monolateral external fixator

BackgroundExternal fixation, which can preserve the biomechanical microenvironment of fracture healing, plays an important role in managing the high-energy fractures with poor surrounding soft tissues. The purpose of this study was to determine the differences of clinical outcomes, if any, between hexapod external fixator and monolateral external fixator in the definitive treatment of high-energy tibial diaphyseal fractures.MethodsA total of 53 patients with high-energy tibial diaphyseal fractures and definitively treated by the hexapod external fixator (HEF) or monolateral external fixator (MEF) were retrospectively collected and analyzed, from March 2015 to June 2019. There were 31 patients in the HEF treatment, and the other 22 patients were managed by the MEF. The demographic data, surgical duration, external fixation time, final radiological results, complications, and clinical outcomes were documented and analyzed. Difficulties that occurred during the treatment were classified according to Paley. The clinical outcomes were evaluated by the Association for the Study and Application of the Method of Ilizarov criteria (ASAMI) at the last clinical visit.ResultsThe mean surgical duration in the HEF group (62.4 ± 8.3 min) was shorter than that in the MEF group (91.4 ± 6.9 min) (P < 0.05). All patients acquired complete bone union finally. Patients in the HEF group (24.2 ± 3.1 weeks) underwent a shorter average external fixation time than that in the MEF group (26.3 ± 3.8 weeks) (P < 0.05). Satisfactory alignment was achieved in all patients without the need for remanipulation. The residual sagittal plane deformities in the HEF group were all less than that in the MEF group (P < 0.05). The complication rate was 35.5% in the HEF group, while 45.5% in the MEF group. There was no statistically significant difference between the two groups in ASAMI scores (P > 0.05).ConclusionThere is no statistically significant difference in finally clinical outcomes between hexapod external fixator and monolateral external fixator in the definitive treatment of high-energy tibial diaphyseal fractures. The hexapod external fixation treatment is a superior effective method, including advantages of stable fixation, less surgical duration, postoperatively satisfactory fracture reduction, and fewer complications.

TRPV4 and PIEZO Channels Mediate the Mechanosensing of Chondrocytes to the Biomechanical Microenvironment.

Articular cartilage and their chondrocytes are physiologically submitted to diverse types of mechanical cues. Chondrocytes produce and maintain the cartilage by sensing and responding to changing mechanical loads. TRPV4 and PIEZOs, activated by mechanical cues, are important mechanosensing molecules of chondrocytes and have pivotal roles in articular cartilage during health and disease. The objective of this review is to introduce the recent progress indicating that the mechanosensitive ion channels, TRPV4 and PIEZOs, are involved in the chondrocyte sensing of mechanical and inflammatory cues. We present a focus on the important role of TRPV4 and PIEZOs in the mechanotransduction regulating diverse chondrocyte functions in the biomechanical microenvironment. The review synthesizes the most recent advances in our understanding of how mechanical stimuli affect various cellular behaviors and functions through differentially activating TRPV4 and PIEZO ion channels in chondrocyte. Advances in understanding the complex roles of TRPV4/PIEZO-mediated mechanosignaling mechanisms have the potential to recapitulate physiological biomechanical microenvironments and design cell-instructive biomaterials for cartilage tissue engineering.

Biomechanical comparison of vertebral augmentation and cement discoplasty for the treatment of symptomatic Schmorl’s node: a finite element analysis

ABSTRACT Percutaneous vertebral augmentation (PVA) and percutaneous cement discoplasty (PCD) are two relatively new minimally invasive surgeries for symptomatic Schmorl's reported in recent decade. However, the clinical evidence for the effectiveness of these two surgeries is insufficient. The purpose of this study was to compare the biomechanical benefits and risks of the two surgeries in order to analyze their biomechanical differences and effectiveness. We reconstructed Five lumbar finite element models via computed tomography data, including control model, PVA-ideal model, PVA-nonideal model, PCD-ideal model, and PCD-nonideal model. The stress and strain of Schmorl's nodes, bone marrow edema zone (BMEZ), affected endplate, and the overall stability of segment were analyzed and compared. The validity of our models was confirmed. As a result, the PVA-ideal model can significantly reduce the stress of Schmorl's node and the strain of BMEZ, while this effect is inappreciable in PVA-nonideal model. The PCD-ideal model significantly reduced the strain of Schmorl's nodes and BMEZ, and significantly improve segmental stability, but also resulted in a significant increase in the stress of Schmorl's nodes, BMEZ and endplates. The PCD-nonideal model not only lacks blocking effect, but also sharply increases the strain of Schmorl's nodes and BMEZ. Thus, We recommend that both PVA and PCD surgeries in ideal distribution facilitated a more stable paranodular biomechanical microenvironment. However, due to the possibility of poor biomechanical outcomes caused by the non-ideal cement distribution, the non-ideal distribution of bone cement needs to be remedied in practice.