Date

2017

Document Type

Dissertation

Degree

Doctor of Philosophy

Department

Molecular Biology

First Adviser

Falk, Matthias M.

Other advisers/committee members

Jain, Himanshu; Cassimeris, Lynne; Iovine, Kathy; Janmey, Paul

Abstract

The medical community is transitioning from replacement to regeneration with the advent of tissue engineering; yet, it is not well understood how cells of the body can interact with the biologically active scaffolds used to guide tissue regeneration. In order to design the ideal material for the regeneration of different tissues, we must first have a comprehensive understanding of the fundamental mechanisms that allow cells to not only attach to these bioscaffold materials, but to also take cues from them as to what tissue should be regenerated. The Jain lab in Lehigh University’s Material Science and Engineering department developed a bioactive glass scaffold with a 70 mol% SiO2 -30 mol% CaO composition, termed TAMP (Tailored Amorphous Multi Porous), for which many parameters of the material may be controlled independently including chemical composition, surface roughness, porosity and pore distribution, and surface area. The worked described here aimed to determine how characteristics of bioactive TAMP scaffolds influence cellular behavior (attachment, morphology, function, proliferation, etc.) and how proteins that absorb to the scaffold surface modify cellular response. Not only did we find that cells attached to the surface and proliferated on and inside the TAMP scaffolds, but we also demonstrate that cells are able to sense and respond to topographical features of their substrate that are 1000 times smaller than the cells themselves. This sensitivity is likely influenced by nano-structure imposed by either the natural glass surface or hydroxyapatite, which forms when glass is exposed to physiological solutions and in-turn influences the confirmation of adsorbed proteins on the surface. Additionally, potential applications for TAMP scaffolds were explored including for hard (bone) tissue, for which we determined that MC3T3-E1 pre-osteoblast cells differentiated using immunofluorescence, qRT-PCR, immunological and enzymatic assays, and BMD pre-cursor cells matured into active osteoclasts. Furthermore, soft tissue applications were explored including analyses of skin regeneration and polarization of uterine epithelium in culture. The data described here highlight the exceptional qualities of this novel scaffold material for tissue engineering applications.

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