Principles of skin regeneration

Mimicking the Hierarchical Organization of Natural Collagen: Toward the Development of Ideal Scaffolding Material for Tissue Regeneration

“…Repair thus leads to the formation of a tissue that is structurally and functionally different from the native one. On the contrary, induced skin regeneration aims to restore the physiologic organ structure and function by using a dermal template (or scaffold) capable of limiting or suppressing spontaneous contraction and scar formation while enabling the synthesis of new dermal tissue ( Yannas, 2009 ; Soller et al, 2012 ). The understanding of mechanotransduction processes revealed to be important in the manufacturing of a temporary scaffold for tissue regeneration, since mechanical stimuli contribute to alterations in the wound healing process and scar formation ( Kuehlmann et al, 2020 ).…”

“…In this regard, two evidence-based mechanisms have been later proposed to explain how the scaffold may hinder contraction, i.e., the reduction of the number of contractile cells (myofibroblasts) in the wound bed and the reduction of the overall contraction forces ( Soller et al, 2012 ). The observed decrease of the number of myofibroblasts in the wound, in the presence of the scaffold ( Murphy et al, 1990 ), could be due to the scaffold ability to non-specifically bind the transforming growth factor beta 1 (TGF-β1), which is a promoter of the myofibroblast phenotype ( Yannas, 2009 ) while preventing platelet aggregation ( Sylvester et al, 1989 ). Indeed, the DRT scaffold is processed by dispersion of bovine tendon collagen in an acid solution, which disrupts the native collagen fiber banding.…”

“…At the same time, a too long persistence of the scaffold would likely interfere with the synthesis of new tissue. Indeed, the inhibition of contraction is necessary but not sufficient for regeneration, since regeneration also requires tissue formation ( Yannas, 2009 ).…”

“…Although requiring further exploration, these findings indicate that the scaffold capability to recapitulate at least some of the structural features of collagen in native dermis may suffice to enhance the scaffold regenerative potential. From a clinical point of view, accelerated angiogenesis is a key factor to improve the outcome of skin regeneration, also considering that the kinetics of angiogenesis is inversely related to the incidence of infections ( Yannas, 2009 ). Therefore, research efforts to improve skin regeneration include the functionalization of cell-free scaffolds with angiogenic molecules, as well as the induction of simultaneous dermis and epidermis regeneration ( Oh et al, 2012 ; do Amaral et al, 2019 ).…”

“…At the same time, a too long persistence of the scaffold would likely interfere with the synthesis of new tissue. Indeed, the inhibition of contraction is necessary but not sufficient for regeneration, since regeneration also requires tissue formation (Yannas, 2009). Based on such observations, the following structural determinants of the scaffold biological activity have been identified (Yannas, 2005), which are mostly linked to the scaffold ability to establish direct interactions with the hosted cells: (a) the chemical composition (i.e., the ligand identity); (b) the mean pore size (i.e., the ligand density); (c) the crosslink density (i.e., the ligand duration); and (d) the local spatial arrangement or microstructure (i.e., the ligand orientation).…”