The Development of a Tissue-Engineered Skin Composite Utilising a Biodegradable Polyurethane Scaffold in a Novel Bioreactor for the Treatment of Extensive, Full-Thickness Burns

Abstract

The fabrication of a laboratory derived skin substitute that promotes epidermal and dermal elements are alternatives that are becoming more widely studied in the field of tissue engineering. Areas of particular interest include significant tissue injuries where skin autograft paucity and donor sites are of concern. The introduction of these products has the potential to reduce the number of surgeries, pain, and scarring for patients with large Total Body Surface Area (TBSA) skin wounds, such as extensive, deep burns. The changes in burn care over the last two decades has seen the percentage of survival burn increase, requiring the need to seek alternative tissue sources. With this in mind, a two stage strategy has been developed to assist with this challenge. The first stage, a biodegradable temporising matrix (BTM) was developed to temporise the wound, followed by the second stage of definitive wound coverage with a laboratory fabricated skin composite, composite cultured skin (CCS). The CCS has been used in pilot animal studies in small wounds (8cm x 8cm) (1, 2), but the concern with large burns is small pieces may leave a patchwork quilt appearance. The primary aim of this thesis is to reduce the need for skin autograft by upscaling the CCS using a bespoke bioreactor system to enable the production of large pieces (25cm x 25cm) for the use in extensive full-thickness burn patients. To assess the CCS, optimisation methods investigating culture techniques to refine and reduce the use of animal products for clinical use were employed. The development of a novel bioreactor was concurrently designed to fabricate large pieces 25cm x 25cm and tested in animal model which led to the first use of this polyurethane derived composite in man, enabling a long-term follow-up of this patient. Further investigations were warranted to overcome pore size of this polymer in later iterations of this dermal template and a hybrid collagen/polyurethane were designed and tested with in vitro and in vivo results showing the potential of a combinational product to overcome the inherent collagen contraction and polyurethane pore size. This thesis provides a translational clinical research story from bench to bedside, it shows the clinical challenges and provides insights into the fabrication of biopolymers for the construction of skin substitutes and their potential use in full-thickness extensive wounds.