Herein, we describe a method for targeting to and retaining intravenously (IV) injected nanoparticles at the site of acute myocardial infarction (MI) in a rat model. Enzyme-responsive peptide-polymer amphiphiles (PPAs) were prepared and assembled as spherical micellar nanoparticles. The resulting nanoparticles respond to matrix metalloproteineases (MMP-2 and MMP-9) that are upregulated in heart tissue post-myocardial infarction. The nanoparticles undergo a morphological transition from spherical-shaped, discrete materials to network-like assemblies when acted upon by MMPs. We show that 15–20 nm, responsive nanoparticles can be injected IV, undergoing reaction with MMPs in the heart after MI, with the resulting assemblies remaining within the infarct for up to 28 days. The initial studies reported here set the stage for the development of targeting systems for therapeutic delivery for acute MI. Critically, with this development, injection of materials is possible via the IV route immediately following MI, resulting in targeted accumulation and long term retention at the site of MI.

Skeletal muscle tissue has an inherent capacity for regeneration following injury. However, severe trauma, such as volumetric muscle loss, overwhelms these natural muscle repair mechanisms prompting the search for a tissue engineering/regenerative medicine approach to promote functional skeletal muscle restoration. A desirable approach involves a bioscaffold that simultaneously acts as an inductive microenvironment and as a cell/drug delivery vehicle to encourage muscle ingrowth. Both biologically active, naturally derived materials (such as extracellular matrix) and carefully engineered synthetic polymers have been developed to provide such a muscle regenerative environment. Next generation naturally derived/synthetic “hybrid materials” would combine the advantageous properties of these materials to create an optimal platform for cell/drug delivery and possess inherent bioactive properties. Advances in scaffolds using muscle tissue engineering are reviewed herein.

Hepatocyte growth factor (HGF) has been shown to have anti-fibrotic, pro-angiogenic, and cardioprotective effects; however, it is highly unstable and expensive to manufacture, hindering its clinical translation. Recently, a HGF fragment (HGF-f), an alternative c-MET agonist, was engineered to possess increased stability and recombinant expression yields. In this study, we assessed the potential of HGF-f, delivered in an extracellular matrix (ECM)-derived hydrogel, as a potential treatment for myocardial infarction (MI). HGF-f protected cardiomyocytes from serum-starvation and induced down-regulation of fibrotic markers in whole cardiac cell isolate compared to the untreated control. The ECM hydrogel prolonged release of HGF-f compared to collagen gels, and in vivo delivery of HGF-f from ECM hydrogels mitigated negative remodeling, improved fractional area change (FAC), and increased arteriole density in rat myocardial infarction model. These results indicate that HGF-f may be a viable alternative to using recombinant HGF, and that an ECM hydrogel can be employed to increase growth factor retention and efficacy.