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Collagen is the main component of the extracellular matrix and it plays a key role in tumor progression. Commercial collagen solutions are derived from animals, such as rat-tail and bovine or porcine skin. Their cost is quite high and the product is stable only at low temperature, with the disadvantage of a short expiring date. Most importantly, lot-to-lot variability can occur and the reconstituted collagen gels differ significantly from native tissues in terms of both structure and stiffness. In this chapter, we describe a straightforward method to use native, collagen rich skin samples derived from by-products of the tanning industry. The protocol proposed preserves the microstructure of the ovine skin collagen network, offering structurally competent and more relevant model to investigate cell behavior in vitro. Other advantages of the proposed procedure consist in the cost-effectiveness of the process and an increased level of reproducibility. The decellularized ovine skin samples support the adhesion and growth of different cancer cell lines (pancreatic, breast and melanoma cells). The proposed decellularized skin scaffolds are meant as future low-cost competitors for conventional porous scaffold derived by biomaterials, since they offer a biomimetic environment for the cells., (© 2020 Elsevier Inc. All rights reserved.)

Myocardial infarction is the leading cause of morbidity and mortality in developed countries. It causes a left ventricular dysfunction, mainly due to the loss of functional tissue, resulting in heart failure. New therapies are being developed, using a tissue engineering approach, with the ultimate goal of restoring cardiac function by regenerating and repairing the damaged myocardium. In the present study we investigated the behaviour of a specific population of c-kit positive human cardiac stem cells, called Multipotent Adult Stem Cells (MASCs), grown within three-dimensional collagen scaffolds (3D), to establish whether they could be used in post-infarction cardiac regeneration. We also evaluated the expression levels of the Granulocyte Macrophage-Colony Stimulating Factor Receptor (GM-CSFR) and endoglin, a component of the Transforming Growth Factor beta (TGF-ß) receptor complex. Finally, we also evaluated the expression of the α2β1integrin. MASCs cultured within 3D collagen matrices are able to proliferate and migrate even in the absence of chemotactic agents and express high levels of factors involved in cell proliferation and migration, such as GM-CSFRα chain and integrins. They therefore represent a promising approach to tissue engineering aimed to restore cardiac function. Our results also suggest a role of GM-CSF in cell proliferation, while TGF-β does not seem to be relevant.

Research on biomaterials and related subjects has been active in Italy. Starting from the very first examples of biomaterials and biomedical devices, Italian researchers have always provided valuable scientific contributions. This trend has steadily increased. To provide a rough estimate of this, it is sufficient to search PubMed, a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics, with the keywords "biomaterials" or "tissue engineering" and sort the results by affiliation. Again, even though this is a crude estimate, the results speak for themselves, as Italy is the third European country, in terms of publications, with an astonishing 3,700 products in the last decade.

The initial conditions for morphogenesis trigger a cascade of events that ultimately dictate structure and functions of tissues and organs. Here we report that surface nanopatterning can control the initial assembly of focal adhesions, hence guiding human mesenchymal stem cells (hMSCs) through the process of self-organization and differentiation. This process self-sustains, leading to the development of macroscopic tissues with molecular profiles and microarchitecture reminiscent of embryonic tendons. Therefore, material surfaces can be in principle engineered to set off the hMSC program toward tissuegenesis in a deterministic manner by providing adequate sets of initial environmental conditions.

Abstract: Angiogenesis occurs through a cascade of events controlled by complex multiple signals that are orchestrated according to specific spatial patterns and temporal sequences. Vascularization is a central issue in most tissue engineering applications. However, only a better insight into spatio-temporal signal presentation can help in controlling and guiding angiogenesis in vivo. To this end, versatile and accessible material platforms are required in order to study angiogenic events in a systematic way. In this work we report a three-dimensional porous polyethylene glycol (PEG) diacrylate hydrogel bioactivated with heparin that is able to deliver vascular endothelial growth factor (VEGF) in a sustained and controlled manner. The efficiency of the material has been tested both in vitro and in vivo. In particular, the VEGF released from the hydrogel induces cell proliferation when tested on HUVECs, retains its bioactivity up to 21days, as demonstrated by Matrigel assay, and, when implanted on a chorion allantoic membrane, the hydrogel shows superior angiogenic potential in stimulating new vessel formation compared with unfunctionalized hydrogels. Moreover, in the light of potential tissue regeneration studies, the proposed hydrogel has been modified with adhesion peptides (RGD) to enable cell colonization. The porous hydrogel reported here can be used as a valid tool to characterize angiogenesis, and, possibly, other biological processes, in different experimental set-ups. [Copyright &y& Elsevier]

Abstract: Understanding the influence of a controlled spatial distribution of biological cues on cell activities can be useful to design “cell instructive” materials, able to control and guide the formation of engineered tissues in vivo and in vitro. To this purpose, biochemical and mechanical properties of the resulting biomaterial must be carefully designed and controlled. In this work, the effect of covalently immobilized RGD peptide gradients on poly(ethylene glycol) diacrylate hydrogels on cell behaviour was studied. We set up a mechanical device generating gradients based on a fluidic chamber. Cell response to RGD gradients with different slope (0.7, 1 and 2mMcm−1) was qualitatively and quantitatively assessed by evaluating cell adhesion and, in particular, cell migration, compared to cells seeded on hydrogels with uniform distribution of RGD peptides. To evaluate the influence of RGD gradient and to exclude any concentration effect on cell response, all analyses were carried out in a specific region of the gradients which displayed the same average concentration of RGD (1.5mM). Results suggest that cells recognize the RGD gradient and adhere onto it assuming a stretched shape. Moreover, cells tend to migrate in the direction of the gradient, as their speed is higher than that of cells migrating on hydrogels with a uniform distribution of RGD and increases by increasing RGD gradient steepness. This increment is due to an augmentation of bias speed component of the mean squared speed, that is, the drift of the cell population migrating on the anisotropic surface provided by the RGD gradient. [Copyright &y& Elsevier]