Influence of deformable substrates on macroscopic and microscopic phenomenon of tissue

Abstract

One of the most important aspects by which cells adapt to their environment is their interaction with their extracellular matrix. The goal of this thesis is to design deformable substrates with controllable mechanical and biochemical properties and to understand cell-substrate interaction at both microscopic and macroscopic scales. First part of the thesis aims to develop biodegradable hydrogels as delivery vehicles for cellular and small molecular therapeutics and also for potential tissue engineering constructs. The second part deals with development of an assessment tool for analyzing changes in tissue mechanics. In the first part of this thesis, we studied the interaction of the dental pulp stem cells with enzymatically crosslinked gelatin hydrogels of tunable stiffness (8KPa-0.1KPa). Dental pulp stem cells (DPSCs) are known to undergo odontogenesis when grown with Dexamethasone (Dex). The purpose of this study was to investigate the odontogenic impact of substrates on DPSCs in the absence of Dex. Through our experiments we identified hydrogels that support DPSC biomineralization and odontogenesis. These scaffolds were self-mineralizing and may prove useful as a biodegradable scaffold for dentin regeneration. In the second part, we prepared physically crosslinked polymer composite hydrogels of variable stiffness. We studied the rheological properties of these hydrogel scaffolds and related it to the type of bonding, degree of crosslinking and mechanical structure of the hydrogels. We showed the successful application of these hydrogels as potential drug delivery vehicles by studying the controlled release of Salicylic Acid. Their potential use as tissue engineered constructs was also shown by dermal fibroblasts adhesion and proliferation. In the last part of this thesis, we successfully developed a non-invasive Digital Image Speckle Correlation (DISC) technique for the precise quantification of the magnitude and duration of facial muscle paralysis inflicted by the Botulinum toxin (BTX-A). We were able to precisely characterize the mechanics of skin abnormalities and macroscopic response of collective cellular motion. Due to the generality of this method we were able to extend the use of DISC for diagnosis and prognosis of patients with vestibular schwannomas. Our results are based on successful human clinical trials of vestibular schwannomas and facial paralysis patients