Enhancement of wound healing efficiency mediated by artificial dermis functionalized with EGF or NRG1

Feb 2, 2018Biomedical materials (Bristol, England)

Improved wound healing using artificial skin treated with EGF or NRG1 proteins

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

INSUREGRAF, an artificial dermis derived from extracellular matrix proteins, shows potential for enhanced wound healing in severe skin injuries.

Acellular dermal matrices from cadavers are prone to infection due to their human origin.
INSUREGRAF minimizes wound contraction and scar formation because of its biocompatibility and mechanical properties.
It does not achieve scar-free healing for full-thickness excisions.
The addition of growth factors like epidermal growth factor (EGF) and neuregulin-1 (NRG1) may enhance skin regeneration.
EGF- or NRG1-functionalized INSUREGRAF effectively recruits fibroblasts and keratinocytes to wound sites.
This functionalized scaffold promotes rapid skin cell proliferation in a specific cellular signaling pathway.

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The use of artificial dermis as a skin substitute is a field of active study, as acellular dermal matrices from cadavers are susceptible to infection owing to their human origin. One such alternative dermal replacement scaffold, INSUREGRAF, is derived primarily from extracellular matrix proteins such as collagen and elastin and has been clinically used to treat severe skin wounds such as burns. This scaffold has proven to be useful to minimize wound contraction and scar formation owing to its biocompatibility, interconnected pore structure, sufficient biodegradability, and suitable mechanical properties. However, INSUREGRAFdoes not provide scar-free wound healing in cases of severe skin damage such as full-thickness (FT) excision. Considering that the efficient recruitment of fibroblasts and keratinocytes into a wound site represents a critical step in the regeneration of damaged skin, we attempted to enhance the efficiency for wound healing by fabricating growth factor-functionalized INSUREGRAF. In particular, we utilized epidermal growth factor (EGF) and an EGF family member, neuregulin-1 (NRG1), not previously studied in the context of wound healing, whose cellular role is to promote proliferation and migration in fibroblasts and keratinocytes. Both artificial dermis-growth factor combinations led to efficient recruitment of fibroblasts and keratinocytes into a wound site during the early steps of skin regeneration. Notably, EGF- or NRG1-functionalized INSUREGRAFinduced rapid proliferation of skin cells in an ERK pathway-dependent manner and exhibited efficient wound healing in a Sprague-Dawley rat FT excision and grafting model. These results provide the foundation for expanding the use of growth factor-functionalized INSUREGRAFto clinical application in cases of severe skin injury. ® ® ® ® ®

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Enhancement of wound healing efficiency mediated by artificial dermis functionalized with EGF or NRG1

Abstract

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