Bioengineering of a novel fibrinalginate scaffold for tissue engineering applications

Over the last few decades, developing reconstructed dermis with the potential of replacing the injured dermis is highly explored. Even though a range of dermal scaffolds are available commercially (Integra® and Matriderm®), none have shown the potential to regenerate injured skin similar to normal skin. Commercially available dermal scaffolds have a range of limitations such as wound contraction, scar formation and poor integration with the host tissue. Designing three dimensional scaffolds using tissue engineering approaches involves optimising the architectural design of the scaffold to promote cell adhesion, proliferation and differentiation to repair the injured tissue. The aim of this thesis was to design a foam-based dermal replacement fibrin-alginate scaffold using surfactants as a tool to introduce gradient porosity within the scaffold (pore range 20 - 270 µm). Initially, a range of non-ionic sugar surfactants were tested on the basis of foaming capacity, stability and their effect on the structure of the fibrin-alginate scaffold. Fibrinalginate scaffolds manufactured using a combination of three sugar based surfactants were highly porous with gradient pore structure, which was confirmed using microscopic techniques. The suitability of this scaffold for the repair of full thickness skin wounds was evaluated using microscopic characterization, viscoelastic measurements, in vitro biocompatibility using human dermal fibroblasts and in vivo testing using a porcine model. Further, this thesis has sought to examine and discuss the challenges faced during the translation phase of the fibrin-alginate technology from the R&D laboratory to a GMP facility for commercial purposes. Moreover, this study also investigated combining the fibrin-alginate technology with synthetic polymers like polydimethylsiloxane and poly(ε-caprolactone) for developing composites with applications for chronic wounds and non-union fractures respectively. A novel immunoassay was designed to comprehend the interfacial binding between the protein and the synthetic polymeric counterpart. This study has increased the current understanding of the use of surfactants on the structural behaviour of foam based protein scaffolds.