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With the increasing use of artificial organs, blood damage has been raising ever more clinical concern. Blood trauma is in fact a major complication resulting from the implantation of medical devices and the use of life support apparatuses. Red blood cells damage predictive models furnish critical information on both the design and the evaluation of artificial organs, because their correct usage and implementation are thought to provide clear and rational guidance for the improvement of safety and efficacy. The currently adopted power-law shear-induced haemolysis prediction model lacks sensitivity with respect to the cumulative effect of previously applied stress magnitudes. An alternative model is proposed where a mechanical quantity was defined, able to describe the blood damage sustained by red cells under unsteady stress conditions, taking into account the load history. The proposed formulation predicted the same trend as the available experimental data. The obtained results have to be considered a preliminary validation of the basic hypothesis of this modified red blood cell damage prediction model. To date, the necessity to design further experiments to validate the proposed damage function clashes with the limitations inherent to current systems to get the time-varying shear stress completely under control.

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In this study, we investigated whether multipotent (human-bone-marrow-derived mesenchymal stem cells [hBM-MSCs]) and pluripotent stem cells (murine-induced pluripotent stem cells [iPSCs] and murine embryonic stem cells [ESCs]) respond to nanocomposite fibrous mats of poly(L-lactic acid) (PLLA) loaded with 1 or 8 wt % of calcium-deficient nanohydroxyapatite (d-HAp). Remarkably, the dispersion of different amounts of d-HAp to PLLA produced a set of materials (PLLA/d-HAp) with similar architectures and tunable mechanical properties. After 3 weeks of culture in the absence of soluble osteogenic factors, we observed the expression of osteogenic markers, including the deposition of bone matrix proteins, in multi/pluripotent cells only grown on PLLA/d-HAp nanocomposites, whereas the osteogenic differentiation was absent on stem-cell-neat PLLA cultures. Interestingly, this phenomenon was confined only in hBM-MSCs, murine iPSCs, and ESCs grown on direct contact with the PLLA/d-HAp mats. Altogether, these results indicate that the osteogenic differentiation effect of these electrospun PLLA/d-HAp nanocomposites was independent of the stem cell type and highlight the direct interaction of stem cell-polymeric nanocomposite and the mechanical properties acquired by the PLLA/d-HAp nanocomposites as key steps for the differentiation process.

Vascular tissue engineering is a relevant research field aimed at elaborating and proposing innovative solutions to overcome the drawbacks related to the use of conventional blood vessel substitutes, especially referring to small-diameter grafts. For this aim, electrospinning can be regarded as a valuable technique to produce novel scaffolds with several functional characteristics that can be usefully tailored for the application discussed here. The reproduction of the natural extracellular matrix obtained by processing bioresorbable polymers, either functionalized or not, is driving the biomedical research towards technical solutions that can lead to an actual therapeutic improvement. In this context, this paper reviews those studies focused on the selection of suitable biomaterials for vascular applications, their microstructure, the cell response to polymeric fibres and the strategies considered so far to modify and therefore enhance the performance of final electrospun scaffolds.

Rapid and controlled vascularization of engineered tissues remains one of the key limitations in tissue engineering applications. This study investigates the possible use of natural extracellular matrix-like scaffolds made of gelatin loaded with human vascular endothelial growth factor (VEGF), as a bioresorbable platform for long-term release and consequent angiogenic boosting. For this aim, gelatin was firstly electrospun and then cross-linked at two different concentrations (0.1% and 0.5% w/v) by using genipin, a low toxic agent, in order to fabricate a suitable substrate to be loaded with VEGF. Collected fibers were homogeneous and free of beads, the fibrous structure was retained after cross-linking. Mechanical properties were deeply affected by the chemical treatment showing a different behavior, depending on the testing conditions (i.e., dry or wet state). VEGF release was assessed by means of ELISA assay: a cumulative release of about 90% (0.1% w/v) and 60% (0.5% w/v) at 28 days was measured. Both VEGF loaded mats induced cell viability, endothelial differentiation and showed chemoattractive properties when tested on human mesenchymal stromal cells (hMSCs). In vitro and in vivo angiogenic assays demonstrated that the VEGF loaded mats induced an angiogenic potential in stimulating new vessel formation similar, if not superior, to fresh VEGF. VEGF retains bioactive and pro-angiogenic potential for up to 14 days. The results demonstrated that genipin cross-linked electrospun gelatin mats loaded with VEGF could be part of a useful strategy to stimulate and induce angiogenesis in tissue engineered applications.

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