A Rapid Fabricated Living Dermal Equivalent for Skin Tissue Engineering: an In-Vivo Evaluation in an Acute Wound Model
Ananta M, Mudera V, Brown RA.
University College London, Institute of Orthopaedics, Stanmore, United Kingdom
The encapsulation of both cells and a surgical mesh in a polymerising collagen hydrogel followed by mechanical compression, after polymerisation, results in the rapid formation of a living dermal equivalent (LDE) with physical properties suitable for in vivo application. It was found in the current study that the LDE supported the attachment, growth, and differentiation of keratinocytes, allowing for the formation of living skin equivalents (LSE) with a monolayer epidermis (LSE-M) and a stratified epidermis (LSE-S). The utility of the LDE for the fabrication of living wound dressings was further evaluated by testing the safety and efficacy of the LSE-M and LSE-S in a lapine model of an acute full thickness skin defect. It was found that the LSE-S significantly stimulated blood vessel formation and accelerated epidermal wound closure compared to controls. The LSE-M showed similar trends but these were not significant. These findings indicate the clinical usefulness of the LDE in the treatment of acute and possibly chronic wounds, such as venous and diabetic ulcerations. The 1-hour fabrication time of the LDE is a significant reduction compared to that of dermal components of current FDA approved dressings, such as Dermagraft, Apligraf and OrCel, which require days to weeks of in vitro culture. It is therefore proposed that the presented method could reduce the high cost associated with the production of living, tissue engineered dressings.
Keratinocytes were isolated from skin tissue taken from the ventral side of the ear lobe from adult male, outbred New-Zealand White (NZW) rabbits