Microengineered Gradient Hydrogels for Mechanobiology

Extracellular biophysical gradients have a profound impact on cell behavior and biological processes during development, wound healing, and disease progression. Stiffness gradient hydrogels engineered to mimic the native extracellular matrix have emerged as powerful tools to probe how cells respond to these varied biophysical cues within their material surroundings, which gives rise to the concept of designer hydrogels to control cell and tissue function. The convergence of material science and microfabrication technologies provides exciting opportunities to identify new mechanobiological understanding and mechanomodulatory therapies by improving the physiological relevance of biomaterials-based experimental platforms. This review reflects on the motivation to investigate stiffness gradients, describes the key considerations for developing application-specific stiffness gradient hydrogel, and summarizes the various approaches that have been introduced to pattern the microscale material properties. The current and emerging applications of stiffness gradient platforms are presented, with particular emphasis on fundamental durotaxis studies, high-throughput screening of cell-material interactions, in vitro disease modeling, and tissue regeneration. The review concludes by discussing the standing challenges and positive trends with the aim of providing directions for future research in microengineered gradient hydrogel technologies.