Volumetric muscle loss injuries overwhelm the endogenous regenerative capacity of skeletal muscle, and the associated oxidative damage can delay regeneration and prolong recovery. This study aimed to investigate the effect of silicon-ions on C2C12 skeletal muscle cells under normal and excessive oxidative stress conditions to gain insights into its role on myogenesis during the early stages of muscle regeneration. In vitro studies indicated that 0.1 mM Si-ions into cell culture media significantly increased cell viability, proliferation, migration, and myotube formation compared to control. Additionally, MyoG, MyoD, Neurturin, and GABA expression were significantly increased with addition of 0.1, 0.5, and 1.0 mM of Si-ion for 1 and 5 days of C2C12 myoblast differentiation. Furthermore, 0.1–2.0 mM Si-ions attenuated the toxic effects of H2O2 within 24 h resulting in increased cell viability and differentiation. Addition of 1.0 mM of Si-ions significantly aid cell recovery and protected from the toxic effect of 0.4 mM H2O2 on cell migration. These results suggest that ionic silicon may have a potential effect in unfavorable situations where reactive oxygen species is predominant affecting cell viability, proliferation, migration, and differentiation. Furthermore, this study provides a guide for designing Si-containing biomaterials with desirable Si-ion release for skeletal muscle regeneration.
Introduction : Skeletal muscle constitutes about 40% of the total body mass and plays a significant role in the movement of the human body. Although skeletal muscles have remarkable endogenous regenerative capacity, this capacity is overwhelmed following acute severe traumatic injuries. Furthermore, the associated oxidative damage can delay regeneration process and prolong recovery. These traumatic injuries result from combat‐ and/or trauma‐induced muscle injuries and often lead to irreversible tissue damage and impaired vascularization. Volumetric muscle loss (VML) is a severe traumatic injury that results in a critical loss (≥ 20%) of the native muscle mass leading to permanent disability. Our hypothesis is that using 3D bioprinted hydrogel modified with silica‐based nanoparticles (NPs) laden human skeletal muscle cells will provide the required architecture and enhance muscle regeneration in VML defects where high levels of reactive oxygen species (ROS) is predominant. Materials and Methods Sodium metasilicate powder was used to adjust and optimize the effective concentration of ionic silicon, while hydrogen peroxide was used as sources of ROS to simulate the oxidative damage conditions of VML injuries. Silica based nanoparticles were embedded into GelMA‐based hydrogels for 3D printing of scaffolds that mimic the skeletal muscle architecture. Results Our preliminary data using ionic silicon indicated that Si‐ions are not cytotoxic to myoblast cells under tested concentrations (0.1‐2.0 mM) (Figure 1). Furthermore, Si‐ions significantly enhanced myoblast cell viability, proliferation, and differentiation into myotubes as indicated by a higher fusion index compared to the control. In‐vitro studies indicated that0.4 mM of H2O2 into the growth media significantly decreases the cell viability after 6 and 24 hr. compared to the control (**p < 0.01, n=4 per group). Addition of 0.5‐1.0 mM of Si into the growth media significantly enhances the cell viability under conditions that mimic high ROS (i.e., H202 treated group). The 3D printed scaffolds of GelMA + NPs indicated a higher myoblast cell viability significantly reducing cell death compared to the bare GelMA scaffolds as shown at Figure 2. Conclusion Our preliminary findings conclude that 0.1 mM Si‐ions enhance myoblast viability, proliferation, and differentiation of C2C12 myoblast cells. Using 0.4 mM of H2O2 can simulate the oxidative damage condition in myoblast cells in‐vitro. Using 0.1‐0.5 mM silicon ions can attenuate the oxidative damage (0.4 mM H2O2) on C2C12 myoblast cells. 3D printed hydrogels loaded with silica‐based nanoparticles are promising materials for 3D printing of muscle constructs.
It is well documented that African Americans (AA) are at a greater risk for the development of hypertension than Caucasian Americans (CA). Our laboratory has recently demonstrated exaggerated transduction of sympathetic nerve activity to blood pressure (BP) in young, healthy AA men compared to CA men. The influence of this greater sympathetic vascular transduction on BP variability is unclear. Although previous studies have reported greater BP variability in AA than CA based on 24‐hr ambulatory BP measurements, to date, no studies have investigated resting BP variability on a beat‐to‐beat basis in AA. Thus, we tested the hypothesis that young AA men would exhibit greater beat‐to‐beat BP variability in comparison to CA men. Heart rate (ECG), and beat‐to‐beat arterial BP (finger photoplethysmography) were continuously measured during a 20‐minute resting period in young, healthy CA (n=15) and AA (n=14) men. The arterial BP waveform was analyzed via Modelflow to estimate stroke volume, and used to calculate cardiac output (CO) and total peripheral resistance [TPR: mean arterial pressure (MAP) divided by CO]. Variance, range, and interquartile range were calculated for MAP, CO and TPR. Data are presented as mean ± standard error (SE). Despite similar average absolute resting systolic BP, diastolic BP, and MAP, compared to CA, AA exhibited larger MAP variance (CA: 19.2±2.6 mmHg2, AA: 32.3±4.0 mmHg2, p=0.009). In addition, the range (CA: 26.9±2.0 mmHg; AA: 33.2±1.8 mmHg, p=0.03) and interquartile range (CA: 5.7±0.4 mmHg; AA: 7.6±0.5 mmHg, p=0.007) of MAP were greater in AA than CA. Similar results were found for both systolic BP and diastolic BP. Interestingly, the variance of CO was not significantly different between groups (P=0.63), whereas the variance of TPR was significantly greater in AA than CA (P=0.03). Likewise, the TPR (but not CO) range, and interquartile range were greater in AA than CA. These findings demonstrate that, relative to CA, AA exhibit greater beat‐to‐beat BP variability which appears to be related to greater variability in TPR. Overall, these greater fluctuations in resting BP may constitute a source of future cardiovascular risk in AA men, and predispose them to the development of hypertension.Support or Funding InformationSupported by NIH R15 HL130906.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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