Synthetic Morphogens and Pro-morphogens for Aided Tissue Regeneration - Biologically Responsive Biomaterials for Tissue Engineering - page 48

Fig. 3.2 Typical histological features of ( a ) healthy skin, ( b ) granulation tissue, ( c ) scar tissue.
Oriented collagen fibres are the main feature of the healthy skin. The granulation tissue is charac-
terised by a high density of small blood vessels, the cross section of which appears as “granules”
throughout the tissue. The scar tissue shows collagen fibres highly packed and disordered when
compared to the healthy tissue

space to new tissue [ 20 ]. The secretion of growth factors by inflammatory cells, the
macrophages, stimulates the formation of a highly vascularised granulation tissue
generally progressing into scar (Fig. 3.2b , c ).
With time, the scar, a tissue characterised by highly packed collagen fibrils,
undergoes remodelling into a tissue that only in some cases and with much delay
resembles the features of the original healthy tissue. The biochemical stimuli
secreted during the healing process recruit mesenchymal cells to the site of injury to
induce not only their proliferation, but also their spatial organisation.
For example, in the case of skin repair, epithelial cell migration and proliferation
are controlled to cover the temporary matrix of the underlying granulation tissue.
Later, in the tissue repair process of the skin the underlying repairing dermis hosts
the mutual stimulation of cells such as keratinocytes and fibroblasts. During the
process, fibroblasts acquire a proliferative phenotype that not only facilitates the site
colonisation but also produce the ECM contraction that facilitates wound closure.
All these activities depend on a tuned balance between the secretion of pro-
inflammatory cytokines and that of growth factors including TGF-alpha; here the
link with embryogenesis becomes evident.
However, spontaneous tissue replace can be achieved only when some conditions
are met:

• The area of damage still includes a macromolecular structure providing a

scaffolding role for migrating and proliferating cells.
The biochemical signalling is not interrupted by excessive distance. •

• The cell activity is not compromised by any pathological unbalance.

In those cases where the area of damage reaches a critical size or alterations of
the biochemical and cellular pathways are caused by pathological conditions (e.g.
diabetes, autoimmune diseases) cell activities including their crosstalk are no longer
able to establish active concentration gradients [ 20 ] .
In the case of disease, precise alterations of the modality of interaction between
growth factors and relative cell receptors have been identified. For example, studies