The effect of thickness and elastic modulus of the anterior talofibular ligament on anterior ankle joint stiffness: A subject-specific finite element study

Ankle sprain is a frequent type of sports injury leading to lateral ligament injury. The anterior talofibular ligament (ATFL) is a primary ligamentous stabilizer of the ankle joint and typically the most vulnerable ligament injured in a lateral ankle sprain (LAS). This study aimed to quantitively investigate the effect of the thickness and elastic modulus of ATFL on anterior ankle joint stiffness (AAJS) by developing nine subject-specific finite element (FE) models under acute injury, chronic injury, and control conditions of ATFL. A 120 N forward force was applied at the posterior calcaneus leading to an anterior translation of the calcaneus and talus to simulate the anterior drawer test (ADT). In the results, the ratio of the forward force to the talar displacement was used to assess the AAJS, which increased by 5.85% in the acute group and decreased by 19.78% in the chronic group, compared to those of the control group. An empirical equation described the relationship between AAJS, thickness, and elastic modulus (R-square 0.98). The equation proposed in this study provided an approach to quantify AAJS and revealed the effect of the thickness and the elastic modulus of ATFL on ankle stability, which may shed light on the potential diagnosis of lateral ligament injury

A finite element analysis of the carpal arch with various locations of carpal tunnel release

ObjectiveThe purpose of this study was to investigate the effects of the location of transverse carpal ligament (TCL) transection on the biomechanical property of the carpal arch structure. It was hypothesized that carpal tunnel release would lead to an increase of the carpal arch compliance (CAC) in a location-dependent manner.MethodsA pseudo-3D finite element model of the volar carpal arch at the distal carpal tunnel was used to simulate arch area change under different intratunnel pressures (0–72 mmHg) after TCL transection at different locations along the transverse direction of the TCL.ResultsThe CAC of the intact carpal arch was 0.092 mm2/mmHg, and the simulated transections ranging from 8 mm ulnarly to 8 mm radially from the center point of the TCL led to increased CACs that were 2.6–3.7 times of that of the intact carpal arch. The CACs after radial transections were greater than those ulnarly transected carpal arches.ConclusionThe TCL transection in the radial region was biomechanically favorable in reducing carpal tunnel constraint for median nerve decompression

Fullerenol inhibits tendinopathy by alleviating inflammation

Tendinopathy is a common disease in orthopaedics, seriously affecting tendon functions. However, the effects of non-surgical treatment on tendinopathy are not satisfactory and surgical treatments possibly impair the function of tendons. Biomaterial fullerenol has been proved to show good anti-inflammatory effects on various inflammatory diseases. For in vitro experiments, primary rat tendon cells (TCs) were treated by interleukin-1 beta (IL-1β) combined with aqueous fullerenol (5, 1, 0.3 μg/mL). Then inflammatory factors, tendon-related markers, migration and signaling pathways were detected. For in vivo experiments, rat tendinopathy model was constructed by local injection of collagenase into Achilles tendons of rats and fullerenol (0.5, 1 mg/mL) was locally injected 7 days after collagenase injection. Inflammatory factors and tendon-related markers were also investigated. Fullerenol with good water-solubility showed excellent biocompatibility with TCs. Fullerenol could increase expression of tendon-related factors (Collagen I and tenascin C) and decrease expression of inflammatory factors (matrix metalloproteinases-3, MMP-3, and MMP-13) and reactive oxygen species (ROS) level. Simultaneously, fullerenol slowed the migration of TCs and inhibited activation of Mitogen-activated protein kinase (MAPK) signaling pathway. Fullerenol also attenuated tendinopathy in vivo, including reduction of fiber disorders, decrease of inflammatory factors and increase of tendon markers. In summary, fullerenol is a promising biomaterial that can be used to treat tendinopathy

Mesenchymal stem cells and porous β-tricalcium phosphate composites prepared through stem cell screen-enrich-combine(−biomaterials) circulating system for the repair of critical size bone defects in goat tibia

Abstract Background Efficacious bone substitute is essential for the treatment of a critical size bone defect. Currently, the bone substitutes commonly used in clinical practice lack osteogenic capacity and the therapeutic efficacy is not ideal. Herein, a novel stem cell screen-enrich-combine(−biomaterials) circulating system (SECCS) was introduced to provide the substitutes with osteogenic ability. The stem cell screening, enrichment, and recombination with substitutes could be integrated during the surgical operation. Using SECCS, the bioactive mesenchymal stem cells (MSCs) and porous β-tricalcium phosphate (β-TCP) composites (MSCs/β-TCP) were rapidly prepared for critical size bone defect repair and validated in goat models of critical size tibia defects. Methods Twelve goats with right hind limb tibia defects of 30 mm were randomly divided into two groups: six (the experimental group) were treated with MSCs/β-TCP prepared by SECCS and the other six goats (the control group) were treated with pure porous β-TCP. The repair effect was assessed by x-ray, computed tomography (CT), micro-CT, histology and histomorphology 6 months after the operation. In addition, the enrichment efficacy of MSCs and the characteristics of the MSCs/β-TCP prepared by SECCS were evaluated. Results The SECCS could compound about 81.3 ± 3.0% of the MSCs in bone marrow to the porous β-TCP without affecting the cell viability. The average number of MSCs for retransplantation was 27,655.0 ± 5011.6 for each goat from the experimental group. In vitro, satisfactory biocompatibility of the MSCs/β-TCP was performed, with the MSCs spreading adequately, proliferating actively, and retaining the osteogenic potential. In vivo, the defect repair by MSCs/β-TCP with good medullary cavity recanalization and cortical remodeling was significantly superior to that of pure porous β-TCP. Conclusions The MSCs/β-TCP prepared through SECCS demonstrated significant therapeutic efficacy in goat models of critical size bone defect. This provides a novel therapeutic strategy for critical size bone defects caused by severe injury, infection, and bone tumor resection with a high profile of safety, effectiveness, simplicity, and ease

Improving Bone Regeneration Using Chordin siRNA Delivered by pH-Responsive and Non-Toxic Polyspermine Imidazole-4,5-Imine

Background/Aims: Bone nonunion remains a challenge for orthopaedists. The technological advancements that have been made in precisely silencing target genes have provided promising methods to address this challenge. Methods: We detected the expression levels of the bone morphogenetic protein (BMP) inhibitors Chordin, Gremlin and Noggin using realtime PCR in bone mesenchymal stem cells (BMSCs) isolated from patients with normal fracture healing and those with bone nonunion. Moreover, we detected the expression of Chordin, Gremlin and Noggin during the osteogenic differentiation of human BMSCs (hBMSCs) using real-time PCR and Western blot. We delivered Chordin siRNA to hBMSCs using a previously reported cationic polymer, polyspermine imidazole-4,5-imine (PSI), as a pH-responsive and non-cytotoxic transfection agent. The apoptosis and cellular uptake efficiency were analysed by flow cytometry. Results: We identified Chordin as the most appropriate potential therapeutic target gene for enhancing the osteogenic differentiation of hBMSCs. Chordin knockdown rescued the osteogenic capacity of hBMSCs isolated from patients with bone nonunion. Highly efficient knockdown of Chordin was achieved in hBMSCs using PSI. Chordin knockdown promoted hBMSC osteogenesis and bone regeneration in vitro and in vivo. Conclusions: Our results suggest that Chordin is a potential target for improving osteogenesis and bone nonunion therapy and that responsive and non-toxic cationic polyimines such as PSI are therapeutically feasible carriers for the packaging and delivery of Chordin siRNA to hBMSCs

Biscarbamate Cross-Linked Low-Molecular-Weight Polyethylenimine for Delivering Anti-chordin siRNA into Human Mesenchymal Stem Cells for Improving Bone Regeneration

Small-interfering RNA (siRNA) provides a rapid solution for drug design and provides new methods to develop customizable medicines. Polyethyleneimine 25 kDa (PEI25kDa) is an effective transfection agent used in siRNA delivery. However, the lack of degradable linkage causes undesirable toxicity, hindering its clinical application. We designed a low-molecular-weight cross-linked polyethylenimine named PEI-Et (Mn:1220, Mw:2895) by using degradable ethylene biscarbamate linkage with lower cytotoxicity and higher knockdown efficiency than PEI25kDa in delivery Chordin siRNA to human bone mesenchymal stem cells (hBMSCs). Suppression of Chordin by using anti-Chordin siRNA delivered by PEI-Et improved bone regeneration in vitro and in vivo associated with the bone morphogenetic protein-2 (BMP-2) mediated smad1/5/8 signaling pathway. Results of this study suggest that Chordin siRNA can be potentially used to improve osteogenesis associated with the BMP-2-mediated Smad1/5/8 signaling pathway and biodegradable biscarbamate cross-linked low-molecular-weight polyethylenimine (PEI-Et) is a therapeutically feasible carrier material to deliver anti-Chordin siRNA to hBMSCs