Glass-activated regeneration of volumetric muscle loss.

Volumetric muscle loss (VML) resulting from injuries to skeletal muscles has profound consequences in healthcare. Current VML treatment based on the use of soft materials including biopolymers and decellularized extracellular matrix (dECM) is challenging due to their incapability of stimulating the formation of satellite cells (SCs), muscle stem cells, which are required for muscle regeneration. Additional stem cells and/or growth factors have to be incorporated in these constructs for improved efficacy. Here we report an approach by using bioactive glasses capable of regenerating VML without growth factors or stem cells. One silicate and two borate compositions with different degradation rates (2.4% for silicate 45S5; 5.3% and 30.4% for borate 8A3B and 13-93B3, respectively, in simulated body fluid (SBF) at 37 °C for 30 days) were used for this study. Our in vitro models demonstrate the ability of ions released from bioactive glasses in promoting angiogenesis and stimulating cells to secrete critical muscle-related growth factors. We further show the activation of SCs and the regeneration of skeletal muscles in a rat VML model. Considering these promising results, this work reveals a potentially simple and safe approach to regenerating skeletal muscle defects. STATEMENT OF SIGNIFICANCE: (1) This is the first report on an inorganic material used in skeletal muscle regeneration through in vitro and in vivo models. (2) Bioactive glass is found to activate the production of satellite cells (SCs), muscle stem cells, without the incorporation of extra stem cells or growth factors. (3) The work represents a simple, safe, low-cost yet efficient means for healing muscle defects.

Chemical Identity and Mechanism of Action and Formation of a Cell Growth Inhibitory Compound from Polycarbonate Flasks.

This paper reports the chemical identity and mechanism of action and formation of a cell growth inhibitory compound leached from some single-use Erlenmeyer polycarbonate shaker flasks under routine cell culture conditions. Single-use cell culture vessels have been increasingly used for the production of biopharmaceuticals; however, they often suffer from issues associated with leachables that may interfere with cell growth and protein stability. Here, high-performance liquid-chromatography preparations and cell proliferation assays led to identification of a compound from the water extracts of some polycarbonate flasks, which exhibited subline- and seeding density-dependent growth inhibition of CHO cells in suspension culture. Mass spectroscopy, nuclear magnetic resonance spectroscopy, and chemical synthesis confirmed that this compound is 3,5-dinitro-bisphenol A. Cell cycle analysis suggests that 3,5-dinitro-bisphenol A arrests CHO-S cells at the G1/Go phase. Dynamic mass redistribution assays showed that 3,5-dinitro-bisphenol A is a weak GPR35 agonist. Analysis of the flask manufacturing process suggests that 3,5-dinitro-bisphenol A is formed via the combination of molding process with γ-sterilization. This is the first report of a cell culture/assay interfering leachable compound that is formed through γ-irradiation-mediated nitric oxide free radical reaction.

Topological principles of borosilicate glass chemistry.

Borosilicate glasses display a rich complexity of chemical behavior depending on the details of their composition and thermal history. Noted for their high chemical durability and thermal shock resistance, borosilicate glasses have found a variety of important uses from common household and laboratory glassware to high-tech applications such as liquid crystal displays. In this paper, we investigate the topological principles of borosilicate glass chemistry covering the extremes from pure borate to pure silicate end members. Based on NMR measurements, we present a two-state statistical mechanical model of boron speciation in which addition of network modifiers leads to a competition between the formation of nonbridging oxygen and the conversion of boron from trigonal to tetrahedral configuration. Using this model, we derive a detailed topological representation of alkali-alkaline earth-borosilicate glasses that enables the accurate prediction of properties such as glass transition temperature, liquid fragility, and hardness. The modeling approach enables an understanding of the microscopic mechanisms governing macroscopic properties. The implications of the glass topology are discussed in terms of both the temperature and thermal history dependence of the atomic bond constraints and the influence on relaxation behavior. We also observe a nonlinear evolution of the jump in isobaric heat capacity at the glass transition when substituting SiO(2) for B(2)O(3), which can be accurately predicted using a combined topological and thermodynamic modeling approach.