Iterative Experimental-Computational Design of Hydrogel Systems for Biomedical Applications

William Marsh Rice University, Houston TX

Investigators

Abstract

This award supports fundamental research on methods for the design of engineered biomaterials. Historically, engineering of biomaterials has focused on biological effects but often ignored the advanced material fabrication and characterization needed to realize the desired biomechanical behavior. This research considers anisotropic and layered hydrogels for tissue engineering applications. The outcome of the research would be a methodology for the design these biomaterials. It integrates manufacturing and biomechanical characterization with the goal to arrive at biomaterials that correspond to complex tissues in the human body. Three target tissues are considered: trachea, intervertebral disks and heart valves. The research outcomes would greatly improve and accelerate the engineering process and thereby make engineered biomaterials more readily available. The outcomes of the research endeavor will also be integrated into educational initiatives through direct involvement of students in research, the development of new educational materials, and mentoring of undergraduate senior design teams. This project's approach is an iterative design methodology for anisotropic and layered hydrogel systems with regional dependent properties. It integrates manufacturing processes, experimental and computational characterization of the microstructured hydrogel systems to arrive at biomaterials that mimic connective tissues. Tissues with fibrous reinforcements (trachea), with layered structure (intervertebral disks), and tissue both patterned and layered (heart valves) are considered. The combined in silico-in vitro design process relies on fundamental advances at the interface between manufacturing, experimental and computational mechanics of soft materials, as well as mathematics. The iterative design starts with the preparation of samples of patterned or layered hydrogels, which will follow the topology of the specific tissue. Molecular weights for layers and for fiber patterns will be chosen such that the global stiffness approximates that of the real tissue in its most common state (e.g., compression for intervertebral disk). Photolithography and staged crosslinking will be used to manufacture materials. Samples will be tested in tension, compression, and bending. Computational models for the biomechanical response will be established which integrate the experimental data through constitutive formulations. Coarse level numerical optimization is performed in a reduced parameter space to approach the target behavior in all possible stress and deformation states encountered by the specific tissues. Further fabrication and experiments on hydrogel systems with more complex heterogeneity are then enabled based on the initial results. Hydrogel systems mimicking the tissue of interest would emerge from exercising the approach in the full parameter space such that optimal topologies and composition are achieved.