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Cardiac fibrosis is considered to be an independent risk factor in the outcome of congestive heart failure. Heart transplantation is the only treatment for patients who are at the end stage of this condition. Shortage of donor organs has created a need for therapeutic alternatives. This dissertation investigates new strategies for cardiac repair systems that could reduce pathological fibrosis and promote growth of myocytes at the site of injury. Design of successful engineered therapies for tissue regeneration relies on discerning how cell behavior can be modulated by chemical and physical cues. Recent studies have shown that external physical cues such as stiffness and geometry can affect cell morphology and function. In this work, the combinatorial effect of stiffness and micro-scale topographical cues on proliferation and gene expression is investigated in 2D and 3D. The 2D system consists of fibroblasts grown on "micropegged" polydimethylsiloxane (PDMS) substrates of different stiffness. The 3D system consists of fibroblasts encapsulated with poly(ethylene glycol) dimethacrylate (PEGDMA) "microrods" of different stiffness in matrigel to create a 3D culture with micro-scale cues of defined mechanical properties in the physiological range. Fibroblasts cultured on micropegged substrates have reduced collagen expression compared to fibroblasts cultured on flat substrates. Cells on stiffer micropegged substrates exhibit down regulation of important regulators of ECM synthesis but there is no down-regulation of these markers when cells are cultured on the softer micropegged substrates. Similarly, three-dimensional cultures with stiffer microrods …