Biological processes (i.e., healing) operate at a multi-component hierarchy. To strengthen the fundamental engineering knowledge of cellular processes for material biocompatibility and tissue engineering, the elucidation of structure-function relationships and control mechanisms of host cells is critical. Our objective is to establish a clinically relevant multifunctional construct that provides several developmental signals to enhance the desirable response of host cells in the reestablishment of normal tissue architecture. Furthermore, this construct provides a microenvironment platform for us to study the mechanisms of soluble and immobilized bioactive factors on affecting cell function. The role of material physicochemical properties on this mediated cell behavior will be ascertained in tandem with the delivery of bioactive factors. We will employ model cell types for selected critical stages of host response to biomaterials (i.e., macrophages for inflammation, fibroblasts for granulation and fibrosis, and keratinocytes for end-stage healing by normal parenchymal cells) and model soluble and immobilized factors (i.e:, growth factors and extracellular matrix protein-derived peptides) as a platform in the study of time-dependent, material- modulated biological response.
Our specific aims are: (1) To develop an in situ photopolymerizable interpenetrating network (IPN) system that consists of modified gelatin and polyethyleneglycol derivatives and contains soluble (i.e., keratinocyte growth factors) and immobilized (i.e., fibronectin derived oligopeptides) biofunctional factors. (2) To establish a mechanistic understanding of the independent and additive effect of aforementioned soluble and immobilized factors on the activation of model cell types (i.e., human blood-derived macrophages, dermal fibroblasts, and keratinocytes) using monoculture and binary cell culture systems. (3) To ascertain IPN efficacy in vivo in modulating the host reaction and healing. ? ? ?
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