UCSF

Ischemic heart disease is the leading cause of death worldwide, accounting for over 16% of deaths each year. While we have succeeded in lowering mortality rates through improved care in the acute setting, treating the chronic morbidities that affect the surviving patient population remains a significant challenge. This has led to rising healthcare costs and increased mortality due to chronic heart failure. In this work, we describe novel micro- and nano-fabricated technologies to manage and treat heart failure. First, we describe the development and application of hyaluronic acid-based polymeric microstructures, termed “microrods”, to attenuate the development of scar tissue following a myocardial infarction and prevent pathological myocardial remodeling. In vitro studies demonstrate the influence of these HA microrods on fibroblasts and cardiomyocyte phenotype, down-regulating key fibrotic indicators. When injected into the infarct zone of adult Sprague-Dawley rats after induction of a myocardial infarction, HA microrods improved cardiac function and preserved the structure of the myocardium as shown by echocardiography and histology, respectively. We then explore novel functionalization of these microrod materials through surface conjugation, drug loading or nanoparticle loading to confer additional therapeutic mechanisms. Lastly, we demonstrate the synthesis and optimization of optical nanoparticle sensors to detect oxygen, glucose and lactate. These sensors are incorporated into tissue-integrating hydrogel scaffolds and can be implanted subcutaneously for continuous sensing to track the progression of heart disease. In summary, we developed several innovative therapeutic strategies utilizing micro- and nanoengineered materials that can be used for comprehensive management and treatment of heart failure.