Phenotypic Modulation of Smooth Muscle Cells on Biodegradable Elastomeric Substrates

Cardiovascular disease is the number one killer in the U.S. Cardiovascular tissue engineering holds enormous potential by providing synthetic materials as vessel replacements. This dissertation focused on the development of novel biodegradable and photo-crosslinkable polymers with controlled surface chemistry, stiffness, and topographical features in regulating smooth muscle cell (SMC) adhesion, proliferation and phenotypic conversion for cardiovascular tissue engineering applications. Chapter II presents a facile synthesis route to obtain a series of photocrosslinkable poly(epsilon-caprolactone) triacrylates (PCLTA) with varied mechanical properties and further demonstrated tunable cell responses using these polymer system. Chapter III demonstrates a model polymer network from PCLTA that can gradually stiffen in 24 h through impeded crystallization at body temperature (37 ºC) and distinct SMC attachment, proliferation and spreading are found. Chapter IV presents the fabrication of a series of PCLTA networks with defined gradients in stiffness for regulation of SMCs behaviors. Chapter V fabricates cylindrical pillars with three different heights of 3.4, 7.4, and 15.1 micrometers by photo-crosslinking PCLTA in silicon molds with predesigned micropatterns. Chapter VI prepared photo-crosslinked PCLTA nanowire arrays with diameters of 20, 100 and 200 nanometers using inorganic nanoporous aluminum oxide (AAO) templates. Chapter VII reports a series of novel poly(L-lactic acid) triacrylates (PLLATAs) networks with same chemical composition but different crystallinity and surface roughness achieved by increasing the annealing time from 0 to 5, 7, 10, and 20 h at 70 ºC. Chapter VIII presents a method for tuning surface chemistry by grafting hydrophilic photocrosslinkable mPEGA chains into the hydrophobic PCLTA at various compositions and reports the smooth muscle cell responses. Chapter IX incorporates poly(L-lysine) (PLL) dangling chains into PCLTA networks at different PLL compositions of 0.5%, 1.0%, 1.5%, and 3%. The surface morphology, hydrophilicity and serum protein adsorption of all these polymer networks were characterized. Primary rat SMCs were cultured on these polymer networks and their attachment, spreading, proliferation, focal adhesions, expression of four contractile gene markers (SM-MHC, smoothlin, transgelin, and calponin) and contractile proteins were characterized systematically. Chapter X makes a summary of these separate investigations and draws general conclusions from the results obtained in these studies.

I developed a series of biodegradable and photocurable polymer networks with tunable mechanical, chemical and topographical features. The influences of these properties were well correlated with cell behavior in terms of adhesion, proliferation and differentiation. Optimized groups of materials were demonstrated that could be served as candidate materials to fabricate injectable supports for cardiovascular tissue engineering applications. Further, these polymer networks owns great potential to find applications in various tissue engineering by achieving advanced functions or more complicated structures.