Epidermolysis Bullosa: A Review of the Tissue-Engineered Skin Substitutes Used to Treat Wounds

Abstract

Skin wound healing is a crucial process for regenerating healthy skin and avoiding the undesired consequences associated with open skin wounds. For epidermolysis bullosa (EB), a debilitating group of fragile skin disorders currently without a cure, skin blistering can often be severe and heal poorly, increasing susceptibility to life-threatening complications. To prevent these, investigational therapies have been exploring the use of tissue-engineered skin substitutes (TESSs) aimed at replacing damaged skin and promoting long-term wound closure. These products have either been developed in house or commercially sourced and are composed of allogeneic or autologous human skin cells, often with some form of bioscaffolding. They can be broadly classified based on their cellular composition: keratinocytes (epidermal substitutes), fibroblasts (dermal substitutes) or a combination of both (composite substitutes). Encouraging long-term wound healing has been achieved with epidermal substitutes. However, these substitutes have not demonstrated the same efficacy for all patients, which may be due to the molecular heterogeneity observed between EB subtypes. Autologous composite TESSs, which more closely resemble native human skin, are therefore being investigated and may hold promise for treating an extended range of patients. Additionally, future TESSs for EB are focused on using gene-corrected patient skin cells, which have already demonstrated remarkable long-term wound healing capabilities. In this review, we provide an overview of the different TESSs that have been investigated in clinical studies to treat patients with EB, as well as their long-term wound healing results. Where available, we describe the methods used to develop these products to inform future efforts in this field.

Biomaterials-mediated CRISPR/Cas9 delivery: recent challenges and opportunities in gene therapy

“…( Jacków et al, 2019 ). The effectiveness and security of CRISPR/Cas9 gene editing might be enhanced by collagen-based delivery methods, and current research in this area is expected to result in future developments ( Prodinger et al, 2019 ; du Rand et al, 2022 ; Wu et al, 2017 ). Collagen-based therapeutic approaches must nevertheless be improved to distribute CRISPR/Cas9 precisely and effectively to target cells.…”

Management of Skin Lesions in Patients with Epidermolysis Bullosa by Topical Treatment: Systematic Review and Meta-Analysis

“…Epidermolysis bullosa (EB), or butterfly skin, is a chronic and incurable hereditary disease caused by an inherited genetic mutation, with a prevalence ratio of 1 individual per 50,000 people, making it classified as a rare disease [ 1 , 2 , 3 , 4 ]. Its systemic clinical manifestations are diverse, leading to nutritional compromise due to gastrointestinal disorders, oral and dental disorders, and abnormalities in the internal epithelial lining in organs [ 5 ].…”

“…As a genodermatosis, it induces fragility, resulting in mucocutaneous blisters, erosions, and ulcers in response to mild trauma or friction. This fragility gives rise to the designation of “butterfly skin” [ 1 , 3 ]. Dermal symptoms are varied, including blisters, ulcersand erosions that easily complicate with any skin trauma, friction, or dryness.…”

Highly efficient CRISPR/Cas9‐mediated exon skipping for recessive dystrophic epidermolysis bullosa

“…They include gene replacement strategies based on the addition of healthy copies of defective genes packaged within integrating viral vectors and delivered into patient cells. These have already progressed to clinical trials for some forms of EB with encouraging results 5 . However, several issues remain, including random genomic integration of the viral vectors, variable transgene expression, and the inability to correct dominant‐negative mutations 6 .…”

“…These have already progressed to clinical trials for some forms of EB with encouraging results. 5 However, several issues remain, including random genomic integration of the viral vectors, variable transgene expression, and the inability to correct dominant‐negative mutations. 6 To bypass these issues, recent efforts have focused on site‐specific, designer nucleases capable of introducing genomic modifications at specific loci.…”