Biological dermal templates with native collagen scaffolds provide guiding ridges for invading cells and may promote structured dermal wound healing

Abstract

Dermal substitutes are of major importance in treating full thickness skin defects. They come in a variety of materials manufactured into various forms, such as films, hydrocolloids, hydrogels, sponges, membranes, and electrospun micro‐ and nanofibers. Bioactive dermal substitutes act in wound healing either by delivery of bioactive compounds or by being constructed from materials having endogenous activity. The healing success rate is highly determined by cellular and physiological processes at the host‐biomaterial interface during crucial wound healing steps. Hence, it is important to design appropriate wound treatment strategies with the ability to work actively with tissues and cells to enhance healing. Therefore, in this study, we investigated biological dermal templates and their potential to stimulate natural cell adherence, guidance, and morphology. The most pronounced effect was observed in biomaterials with the highest content of native collagen networks. Cell attachment and proliferation were significantly enhanced on native collagen scaffolds. Cell morphology was more asymmetrical on such scaffolds, resembling native in vivo structures. Importantly, considerably lower expression of myofibroblast phenotype was observed on native collagen scaffolds. Our data suggest that this treatment strategy might be beneficial for the wound environment, with the potential to promote improved tissue regeneration and reduce abnormal scar formation.

Natural-Based Biomaterial for Skin Wound Healing (Gelatin vs. Collagen): Expert Review

“…With regard to this, the native col scaffold has been proven effective for cell attachment and proliferation, particularly at the wound site. Interestingly, the cells at the wound site appeared to be symmetrical and aligned in accordance with the native Col scaffold [ 77 ]. Nonetheless, an in vitro study proved that col scaffolds successfully accelerated healing by enhancing proliferation of fibroblasts [ 78 ] by increasing biological and structural integrities which resembled the native extracellular matrix (ECM) at the wound site [ 79 ].…”

“…Being biocompatible, they are beneficial and superior compared to other available natural products. Col is naturally found in the human body while gelatin is a hydrolysed form of Col. Studies done by Dill and Morgelin (2020) [ 77 ] and Wiegand et al, (2016) [ 87 ] showed that native Col provided a 3D microenvironment that stimulated cell proliferation and aided the migration of keratinocytes and fibroblasts to the physiologic locations during wound healing. Through their in vitro investigations, they noticed that fibroblasts and keratinocytes attached to Col with high affinities.…”

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

“…With regard to pore size and crosslink density, it is worth mentioning that the optimal values found by the Yannas team for their DRT are currently used as a gold standard for the development of alternative dermal substitutes. However, the DRT does not present the native collagen banding (it is estimated to have only a 5% residual banding) (Yannas, 2005) while having a microporous sponge-like structure that does not really mimic the fibrillar network of the skin ECM (Dill and Mörgelin, 2020). This relatively poor mimesis of the native collagen architecture may be one of the critical features leading to suboptimal skin regeneration.…”

“…Indeed, more recent studies seem to suggest that the preservation of the native tissue structure is highly desirable for improved skin regeneration (Böhm et al, 2017;De Angelis et al, 2018;Tati et al, 2018;Dill and Mörgelin, 2020). When comparing different collagen-based dermal substitutes, all obtained by freeze-drying but varying for the collagen source and the related processing steps (e.g., collagen extraction, aqueous processing, and crosslinking), those with a dermislike fibrillar network and/or those retaining the native collagen banding have been shown to promote in vitro important biological processes involved in tissue regeneration, such as the binding and inactivation of proteases (Tati et al, 2018), an accelerated adhesion, migration and proliferation of cells in the scaffolds (Böhm et al, 2017;Dill and Mörgelin, 2020), an improved cell morphology (Dill and Mörgelin, 2020), and a higher downregulation of the myofibroblast phenotype (Dill and Mörgelin, 2020). Interestingly, in a recent clinical study, an alternative dermal template based on native type I collagen has been shown to lead to accelerated angiogenesis and tissue formation in the short term, as well as to a better clinical outcome in the long term, compared to the Integra R DRT (De Angelis et al, 2018).…”

Antibacterial and wound healing activities of silver nanoparticles embedded in cellulose compared to other polysaccharides and protein polymers

“…Collagen Collagen has been found as the frequent protein in terrestrial and marine animals with desirable tensile strength, biocompatibility, bioavailability, and biodegradability properties for various therapeutic applications particularly tissue engineering (Lim et al 2019;Divakar et al 2019). Scaffold of collagen can attract and guide the migration of broblast cells along a connective tissue matrix (Dill and Mörgelin 2020). By interaction with blood platelets, this polymer can lead to the wound closure and prompt the acceleration of hemostatic phase of wound healing (Ding et al 2020).…”