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This underlines the complexity in the realization of a scaffold and all the studies necessary to achieve
a structure similar to physiological ECMs. Nowadays, numerous approaches are used for designing
matrices, consisting of increasingly innovative biomaterials. Until recently, the only two
characteristics that a biomaterial had to possess were biocompatibility (the material must be neither
cytotoxic nor immunogenic) and biodegradability (the material must be easily eliminated once its
function is fulfilled). However, in the modern sense of biomaterials, we must also add the ability to
interface with a biological environment and specifically modulate cellular response. The biomaterial
becomes, therefore, not only a support for tissue regeneration or a platform for drug delivery, but an
active part of cellular function regulation. Based on these assumptions, different parameters have to
be taken into consideration such as the physico‐chemical properties of pristine materials, mechanical
properties, scaffold shape, structure, pore sizes and their distribution.
Figure 4. Schematic representation of classical tissue engineering approach.
5.1.1. Structural Characteristics
Skin architectural and mechanical complexity and its properties depend on specific anatomical
regions, making scaffold design and production challenging. [90]. Scaffold physico‐chemical
characterization involves morphology, porosity, water contact angle, mechanical properties,
chemical bonds, stability upon incubation in simulated physiological fluids and cell culture
medium, while in vitro
biological characterization addresses the testing adhesion, adhesion and
migration of human cells. To assess these aspects, indirect analyses of immunofluorescence, confocal
laser scanning microscopy (CLSM), environmental scanning electron microscopy (ESEM),
transmission electron microscopy (TEM) and rheological measurements are conducted. Matrix
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