GRADIENT POROUS FIBROUS SCAFFOLDS AS A PARADIGM FOR IMMUNOMODULATORY WOUND DRESSINGS

Abstract

Engineering therapeutic approaches to wound healing can be divided into two major categories of fibrous and non-fibrous approaches. There has been significant progress in designing artificial skin products to replace autografting. For patients with non-healing/hard-to-heal wounds, there is an unmet clinical need for inexpensive skin substitutes to be transplanted. In skin regeneration area of research, electrospinning is a very commonly used method of production of grafts for wound healing applications, owing its popularity to the fibrous nature of the resultant product, which mimics the extracellular matrix of the native skin. Despite the high degree of porosity in conventional electrospun scaffolds, the small pore size effectively limits the penetration of cells into the scaffold. Transplantation of such scaffolds with poor cell infiltration abilities may lead to a range of negative consequences, from prolongation of the first/destructive phase of inflammation to rejection of the scaffolds. Several experimental approaches have been developed to generate interfibrillar space in the electrospun scaffolds, including but not limited to modifications of the electrospinning set-up and inclusion of sacrificial components. It has been reported that scaffolds with larger pore diameters in the range of ~ 40-100 μm can modulate, moderate and reduce acute inflammatory responses of the body, by influencing macrophages biological behavior, and direct the course of the wound healing process to the tissue remodeling phase. Macrophages are the major cell component of innate immune system and play critical roles in clearance of pathogens, resolution of inflammation and wound healing following an injury. Macrophages are characterized by their diversity and plasticity. In response to environmental stimuli, they acquire different functional phenotypes of pro-inflammatory (M1) or anti-inflammatory (M2). In this thesis, we developed a novel unique gradient porous structure from a plant-based “green” soy protein isolate (SPI) with improved pore size for macrophages to infiltrate. We further showed the ability of the scaffold to modulate phenotype switch in macrophages in vitro and in vivo. The proposed scaffold, moreover, appeared to support transition of the inflammation process from the destructive to the constructive phase in vivo. Based on the promising results of this thesis, we propose our newly developed scaffold has the ability to be used as a new therapeutic modality for treatment of non-healing chronic wounds.