Biomimetic Injectable Hydrogel Based on Methacrylate-Modified Silk Fibroin Embedded with Kartogenin for Superficial Cartilage Regeneration.

The weak regeneration ability of chondrocytes is one of the main reasons that limit the therapeutic effect of clinical cartilage injury. Injectable hydrogels are potential scaffolds for cartilage tissue engineering with advantages such as minimally invasive surgery, porous structure, and drug sustained-release ability. At present, many biomaterials have been developed for the repair of deep cartilage defects. However, cartilage injury often begins on the surface, which requires us to propose a treatment strategy suitable for superficial cartilage injury repair. In this study, we fabricated a biomimetic injectable hydrogel based on methacrylate-modified silk fibroin (SilMA) embedded with kartogenin (KGN). The SilMA/KGN hydrogels have good biohistocompatibility and the ability to promote cartilage differentiation. In addition, SEM results show that it has a porous structure conducive to cell adhesion and proliferation. Most importantly, it has demonstrated remarkable superficial cartilage repair ability in vivo, showing potential in cartilage tissue engineering.

The efficacy and safety of low-molecular-weight heparin in patients undergoing knee arthroscopic surgery and anterior cruciate ligament reconstruction.

Purpose: To inveatigate how effective LMWH was at preventing venous thromboembolism (VTE), major bleeding events, and minor bleeding events after simple knee arthroscopic surgery and anterior cruciate ligament reconstruction (ACLR). Methods: We conducted a comprehensive search of PubMed, EMBASE, Cochrane Library, and the CNKI database for potentially eligible articles. The outcomes were evaluated in terms of odds ratio (OR) and the associated 95% confidence intervals (CIs). Meta-analysis was performed using the Stata software and subgroup analyses were performed based on the surgical setting including ACLR and simple knee arthroscopic surgery. Results: A total of eight studies with 2249 patients and 1794 controls were included in this meta-analysis. In patients undergoing simple knee arthroscopic surgery, LMWH prophylaxis did not bring a significant reduction in the risk of symptomatic deep venous thrombosis (DVT), symptomatic pulmonary embolism (PE), symptomatic VTE, and did not increase the risk of major bleeding events, but did have a higher risk of minor bleeding events (OR = 1.95, 95% CI 1.34-2.84, P = 0.000) and a lower risk of asymptomatic DVT (OR = 0.14, 95% CI 0.04-0.53, P = 0.004) in comparison with non-LMWH prophylaxis. In patients undergoing ACLR, LMWH prophylaxis did not bring a significant reduction in the risk of symptomatic DVT, symptomatic PE, symptomatic VTE, and did not increase the risk of major bleeding events and minor bleeding events, but did have a lower risk of asymptomatic DVT (OR = 0.43, 95% CI 0.23-0.78, P = 0.006). Conclusion: When compared to a control group, this meta-analysis found that LMWH had little potential benefit in preventing major VTE (symptomatic VTE, symptomatic DVT, and symptomatic PE) after simple knee arthroscopy and ACLR. As a result, LMWH should not be considered routinely in patients undergoing knee arthroscopic surgery.

Chondroitin Sulfate Improves Mechanical Properties of Gelatin Hydrogel for Cartilage Regeneration in Rats.

Cartilage injury is a common disease in daily life. Especially in aging populations, the incidence of osteoarthritis is increasing. However, due to the poor regeneration ability of cartilage, most cartilage injuries cannot be effectively repaired. Even cartilage tissue engineering still faces many problems such as complex composition and poor integration of scaffolds and host tissues. In this study, chondroitin sulfate, one of the main components of extracellular matrix (ECM), is chosen as the main natural component of the material, which can protect cartilage in a variety of ways. Moreover, the results show that the addition of chondroitin sulfate improves the mechanical properties of gelatin methacrylate (GelMA) hydrogel, making it able to effectively bear mechanical loads in vivo. Further, chondroitin sulfate is modified to obtain the oxidized chondroitin sulfate (OCS) containing aldehyde groups via sodium periodate. This special group improves the interface integration and adhesion ability of the hydrogel to host cartilage tissue through schiff base reactions. In summary, GelMA/OCS hydrogel is a promising candidate for cartilage regeneration with good biocompatibility, mechanical properties, tissue integration ability, and excellent cartilage repair ability.

Aspirin prevents estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis and promoting osteogenesis.

BACKGROUND: Aspirin is a commonly used antipyretic, analgesic, and anti-inflammatory drug. Numerous researches have demonstrated that aspirin exerts multiple biological effects on bone metabolism. However, its spatiotemporal roles remain controversial according to the specific therapeutic doses used for different clinical conditions, and the detailed mechanisms have not been fully elucidated. Hence, in the present study, we aimed to identify the dual effects of different aspirin dosages on osteoclastic activity and osteoblastic bone formation in vitro and in vivo. METHODS: The effects of varying doses of aspirin on osteoclast and osteoblast differentiation were evaluated in vitro. The underlying molecular mechanisms were detected using quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence techniques. An ovariectomized rat osteoporosis model was used to assess the bone-protective effects of aspirin in vivo. RESULTS: Aspirin dose-dependently suppressed RANKL-induced osteoclasts differentiation and bone resorption in vitro and reduced the expression of osteoclastic marker genes, including TRAP, cathepsin K, and CTR. Further molecular analysis revealed that aspirin impaired the RANKL-induced NF-κB and MAPK signaling pathways and prevented the nuclear translocation of the NF-κB p65 subunit. Low-dose aspirin promoted osteogenic differentiation, whereas these effects were attenuated when high-dose aspirin was administered. Both low and high doses of aspirin prevented bone loss in an ovariectomized rat osteoporosis model in vivo. CONCLUSION: Aspirin inhibits RANKL-induced osteoclastogenesis and promotes osteogenesis in a dual regulatory manner, thus preventing bone loss in vivo. These data indicate that aspirin has potential applications in the prevention and treatment of osteopenia.

'Skywalker' surgical robot for total knee arthroplasty: An experimental sawbone study.

BACKGROUND: Currently, robot-assisted surgical systems are used to reduce the error range of total knee arthroplasty (TKA) osteotomy and component positioning. METHODS: We used 20 sawbone models of the femur and 20 sawbone models of the tibia and fibula to evaluate the osteotomy effect of 'Skywalker' robot-assisted TKA. RESULTS: The maximal movement of the cutting jig was less than 0.25 mm at each osteotomy plane. The mean and standard deviation values of the angle deviation between the planned osteotomy plane and the actual osteotomy plane at each osteotomy plane were not more than 1.03° and 0.55°, respectively. The mean and standard deviation values of absolute error of resection thickness at each osteotomy position were less than 0.78 and 0.71 mm, respectively. CONCLUSIONS: The 'Skywalker' system has good osteotomy accuracy, can achieve the planned osteotomy well and is expected to assist surgeons in performing accurate TKA in clinical applications in future.

TiO2 nanotubes regulate histone acetylation through F-actin to induce the osteogenic differentiation of BMSCs.

Bone integration on the surface of titanium prosthesis is critical to the success of implant surgery. Good Bone integration at the contact interface is the basis of long-term stability. TiO2 nanotubes have become one of the most commonly used modification techniques for artificial joint prostheses and bone defect implants due to their good biocompatibility, mechanical properties and chemical stability. TiO2 nanotubes can promote F-actin polymerization in bone mesenchymal stem cells (BMSCs) and osteogenic differentiation. The possibility of F-actin as an upstream part to regulate GCN5 initiation of osteogenesis was discussed. The results of gene loss and functional acquisition assay, immunoblotting assay and fluorescence staining assay showed that TiO2 nanotubes could promote the differentiation of BMSCs into osteoblasts. The intervention of TiO2 nanotubes can make BMSCs form stronger F-actin fibre bundles, which can drive the differentiation process of osteogenesis. Our results showed that F-actin mediated nanotube-induced cell differentiation through promoting the expression of GCN5 and enhancing the function of GCN5 and GCN5 was a key regulator of the osteogenic differentiation of BMSCs induced by TiO2 nanotubes as a downstream mediated osteogenesis of F-actin, providing a novel insight into the study of osteogenic differentiation on surface of TiO2 nanotubes.

Interannual variation, ecological risk and human health risk of heavy metals in oyster-cultured sediments in the Maowei Estuary, China, from 2011 to 2018.

Heavy metals (HMs) in aquaculture-influenced sediments pose a threat to both aquatic ecosystems and human health via aquatic product intake. Based on a long-term (from 2011 to 2018) study, the concentrations of five HMs in oyster-cultured sediments in the Maowei Estuary, China, were ranked as follows: Pb (17.58 ± 10.82 mg/kg) > Cu (17.15 ± 8.61 mg/kg) > As (10.27 ± 5.24 mg/kg) > Cd (0.16 ± 0.14 mg/kg) > Hg (0.067 ± 0.033 mg/kg). These concentrations were all close to the guide values in China and those reported in other studies. However, through the Mann-Kendall test, Cu showed obvious increasing interannual trends, and according to ecological risk assessment, the sediments were highly contaminated with Cu and Hg. The health risks to local residents via oyster intake showed that both noncarcinogenic and carcinogenic risk did not exceed the safety criteria (THQ = 1, TCR = 10-6). The current study suggests that ecological and human health risks be integrated to control HMs in the Maowei Estuary.

Mechanical strain promotes osteogenic differentiation of mesenchymal stem cells on TiO2 nanotubes substrate.

Previous studies demonstrated cycle mechanical strain induced osteogenic differentiation of MSCs. But in general, MSCs are typically seeded on a flexible membrane or within a soft matrix. TiO2 nanotubes substrate topography plays a critical role in promoting the MSCs response and affects MSCs fate. Titanium implants surface modified by TiO2 nanotubes topography provides the opportunity to improve osseointegration by additionally regulating the MSCs fate. Titanium is one of most commonly used materials in the orthopedics and can undergo elastic deformation under certain mechanical stress. Therefore, for clinic trails, it is necessary to investigate the effect of mechanical strain on osteogenesis of MSCs on TiO2 nanotubes modified titanium substrate. But until now, there has been no research focused on the relationship between mechanical strain and osteogenesis of MSCs on the TiO2 nanotubes topography substrate. Here, we firstly applied the mechanical stress to the TiO2 nanotubes modified titanium specimen to investigate the effects of mechanical strain on the biological behaviors of MSCs. Our present study showed that mechanical strain promoted cell proliferation, spreading and increased vinculin expression of MSCs on the TiO2 nanotubes substrate. Additionally, mechanical strain enhanced the ALP activity and osteogenesis genes expression such as Runx2, BSP, ALP, OPN and OCN. Our results preliminarily demonstrated that mechanical strain enhanced the osteogenic differentiation of MSCs through the FAK-Erk1/2-Runx2 pathway on the TiO2 nanotubes substrate.