Repairing cardiac tissue after myocardial infarction (MI) is one of the most challenging goals in tissue engineering. Following ischemic injury, significant matrix remodeling and the formation of avascular scar tissue significantly impairs cell engraftment and survival in the damaged myocardium. This limits the efficacy of cell replacement therapies, demanding strategies that reduce pathological scarring to create a suitable microenvironment for healthy tissue regeneration. Here, we demonstrate the successful fabrication of discrete hyaluronic acid (HA)-based microrods to provide local biochemical and biomechanical signals to reprogram cells and attenuate cardiac fibrosis. HA microrods were produced in a range of physiological stiffness and shown to degrade in the presence of hyaluronidase. Additionally, we show that fibroblasts interact with these microrods in vitro, leading to significant changes in proliferation, collagen expression and other markers of a myofibroblast phenotype. When injected into the myocardium of an adult rat MI model, HA microrods prevented left ventricular wall thinning and improved cardiac function at 6 weeks post infarct.

Diabetes is affecting the life of millions of people. A large proportion of diabetic patients suffer from severe complications such as neuropathic pain, and current treatments for these complications have deleterious side effects. Thus, alternate therapeutic strategies are needed. Recently, the elevation of epoxy-fatty acids through inhibition of soluble epoxide hydrolase (sEH) was shown to reduce diabetic neuropathic pain in rodents. In this report, we describe a series of newly synthesized sEH inhibitors with at least 5-fold higher potency and doubled residence time inside both the human and rodent sEH enzyme than previously reported inhibitors. These inhibitors also have better physical properties and optimized pharmacokinetic profiles. The optimized inhibitor selected from this new series displayed improved efficacy of almost 10-fold in relieving pain perception in diabetic neuropathic rats as compared to the approved drug, gabapentin, and previously published sEH inhibitors. Therefore, these new sEH inhibitors could be an attractive alternative to treat diabetic neuropathy in humans.