Fine-tuning of substrate architecture and surface chemistry promotes muscle tissue development

Tissue engineering has been increasingly brought to the scientific spotlight in response to the tremendous demand for regeneration, restoration or substitution of skeletal or cardiac muscle after traumatic injury, tumour ablation or myocardial infarction. In vitro generation of a highly organized and contractile muscle tissue, however, crucially depends on an appropriate design of the cell culture substrate. The present work evaluated the impact of substrate properties, in particular morphology, chemical surface composition and mechanical properties, on muscle cell fate. To this end, aligned and randomly oriented micron (3.3±0.8 μm) or nano (237±98 nm) scaled fibrous poly(ε-caprolactone) non-wovens were processed by electrospinning. A nanometer-thick oxygen functional hydrocarbon coating was deposited by a radio frequency plasma process. C2C12 muscle cells were grown on pure and as-functionalized substrates and analysed for viability, proliferation, spatial orientation, differentiation and contractility. Cell orientation has been shown to depend strongly on substrate architecture, being most pronounced on micron-scaled parallel-oriented fibres. Oxygen functional hydrocarbons, representing stable, non-immunogenic surface groups, were identified as strong triggers for myotube differentiation. Accordingly, the highest myotube density (28±15% of total substrate area), sarcomeric striation and contractility were found on plasma-coated substrates. The current study highlights the manifold material characteristics to be addressed during the substrate design process and provides insight into processes to improve bio-interfaces.

Variability in outcome and resource use in intensive care units

OBJECTIVE: To examine variability in outcome and resource use between ICUs. Secondary aims: to assess whether outcome and resource use are related to ICU structure and process, to explore factors associated with efficient resource use. DESIGN AND SETTING: Cohort study, based on the SAPS 3 database in 275 ICUs worldwide. PATIENTS: 16,560 adults. MEASUREMENTS AND RESULTS: Outcome was defined by standardized mortality rate (SMR). Standardized resource use (SRU) was calculated based on length of stay in the ICU, adjusted for severity of acute illness. Each unit was assigned to one of four groups: "most efficient" (SMR and SRU < median); "least efficient" (SMR, SRU > median); "overachieving" (low SMR, high SRU), "underachieving" (high SMR, low SRU). Univariate analysis and stepwise logistic regression were used to test for factors separating "most" from "least efficient" units. Overall median SMR was 1.00 (IQR 0.77-1.28) and SRU 1.07 (0.76-1.58). There were 91 "most efficient", 91 "least efficient", 47 "overachieving", and 46 "underachieving" ICUs. Number of physicians, of full-time specialists, and of nurses per bed, clinical rounds, availability of physicians, presence of emergency department, and geographical region were significant in univariate analysis. In multivariate analysis only interprofessional rounds, emergency department, and geographical region entered the model as significant. CONCLUSIONS: Despite considerable variability in outcome and resource use only few factors of ICU structure and process were associated with efficient use of ICU. This suggests that other confounding factors play an important role.