Date of Award

2010

Degree Type

Dissertation

Department

Chemical and Biomedical Engineering

First Advisor

Roy, Shuvo

Subject Headings

Bone marrow, Stem cells, Bone regeneration, Tissue engineering, Bone graft, Bone marrow derived stem cell, PDMS, Microfabrication, Soft lithography

Abstract

The ultimate goal of this project is to develop a biodegradable and implantable scaffold with precise surface topographies that can provide osteoconductive stimuli to connective tissue progenitor cells (CTPs), and subsequently, enhance bone regeneration applications without the complications of autogenous cancellous bone grafts. This dissertation presents the modification of surface microtextures to provide osteoconductive stimuli to CTPs for bone regeneration applications. First, the effect of surface topography on cell proliferation and osteogenic differentiation was validated through experiments using surface post microtextures and CTPs. Post microtextures accelerated CTP growth behaviors compared to smooth polydimethylsiloxane (PDMS) and standard cell culture dishes. Second, soft lithographic techniques were used to develop PDMS post microtextures with varying geometry and arrangement. 10 um diameter post microtextures with various inter-spaces (5, 10, 20, and 40 um) and post heights (5, 10, 20, and 40 um) were developed, and cultured with CTPs to establish optimal and precise surface post microtextures that can provide CTPs with an osteoconductive environment. Cells on post microtextures with 10 um height and 10 um inter-space exhibited higher cell number than other micro-posts with different heights or inter-spaces, and smooth surfaces. The results demonstrate a significant response of CTPs to topography, and suggest a practical role for optimal post size on textured materials in modifying CTP behavior. Third, substrate stiffness of various PDMS formulations was analyzed to investigate the effects on morphology, proliferation, and osteogenic differentiation of CTPs. Stiffer PDMS substrates with surface microtextures provided an enhanced osteoconductive microenvironment to CTPs relative to softer PDMS substrates. Finally, soft lithography techniques were successfully applied to biodegradable materials, including cellulose acetate (CA) and poly lactic-co-glycolic acid (PLGA). More specifically, CTPs on CA an

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