Three-dimensional electrospun constructs for wound healing applications

This thesis embraces the opportunity to develop a wound dressing substrate that not only attends the functional requirements of a wound dressing, but also avoids the need of secondary dressings. Novel electrostatically driven self-assembled fibrous based materials made of poly(ε-caprolactone) are manufactured, resulting in asymmetrical materials with enhanced topographies. Such constructs are characterized by a flat bottom side and a top side populated with fibrous-based microsized protrusions, which have a median inter-protusion distance of 528 μm and a median peak density of 73 peaks per cm2. For the first time, it is provided a full explanation of the underlying fabrication phenomena, suggesting new routes to other polymers such as gelatin or chitosan. After the characterization of the proposed substrates, such materials are functionalized by layer-by-layer. Several combinations of polyelectrolytes (chitosan, gelatin, alginate, hyaluronic acid, poly-1, linear polyethyleneimine and dextran sulphate) and layer numbers (n = 1, 3, 5 or 10) are tested regarding the physicochemical properties of the generated multi-layered films, as well as the cellular adhesion on these constructs. It is intended to formulate, test and control, the underlying phenomena that avoids the cellular adhesion and proliferation within the used dressing. As prepared these materials are capable of withstanding (11.0 ± 0.3)×104 kg per m2 after 14 days of hydration. Their unique asymmetry promotes unidirectional liquid uptake (from the top side towards the inner structure of the materials), while being impermeable to potential external liquid-forms of infection at its bottom side. Nevertheless, such constructs also observed the high porosity (89.9%) and high surface area (1.44 m2.g-1) characteristic of traditional electrospun mats. The selected coating reduced cellular adhesion on the constructs throughout the generation of a rubbery film layer, which would also provide a means to tailor water vapor transmission and swelling ratio for different wound environments specifications (e.g. ischemic wounds, I/II/III-degree burns, etc.). As a showcase, functionalized wound dressing substrates were able to achieve 90 ± 0.5 % of wound closure within 48 hours