UC San Diego

Chronic heart failure (CHF) and traumatic brain injury (TBI) are among the most commonpathologies that afflict Americans today. While CHF and TBI affect different organs, they share the fact that both patient populations face a great unmet need for a therapeutic that aims to regenerate or preserve organ function. Thus, we investigated the use of two different types of ECM derived biomaterials for the treatment of chronic myocardial infarction (MI) and acute TBI. First, we investigated the efficacy and mechanism of action of an injectable myocardial matrix hydrogel in a chronic model of MI. In these studies, we showed the ability of the matrix to preserve cardiac function as well as its ability to modulate gene expression through methods of medium and high throughput gene expression analyses. Next, we moved onto a new ECM derived biomaterial that isolates the low molecular weight components of a traditional myocardial matrix hydrogel to create an infusible ECM biomaterial (iECM). Applying this iECM in an acute model of TBI, we found that the material can modulate vascular permeability and BBB integrity through methods of in vivo and in vitro assessments. While the iECM was not shown to improve sensorimotor function on rotarod, we did see modulation of the neuroinflammatory response as well as a neuroprotective response via gene expression analyses. These studies together have advanced the understanding of ECM therapeutics in chronic MI as well as shown the importance of BBB and vascular integrity in modulating neuroinflammation in acute TBI using a new type of ECM biomaterial.