Abstract

Cardiovascular diseases remain the leading cause of mortality worldwide, with myocardial infarction (MI) and heart failure (HF) accounting for a substantial proportion of morbidity and healthcare burden. Despite current progresses in treating MI and HF, they have limited ability to directly modulate pathological remodeling, regenerate damaged myocardium, or reverse established fibrosis. Biomaterial-based delivery systems offer opportunities to enhance therapeutic retention, targeting efficiency, and biological efficacy in cardiovascular diseases. In this dissertation, targeted biomaterial platforms were developed to address key pathological processes in MI and HF, including inflammation, cardiomyocyte loss, impaired vascularization, and fibrosis. In Chapter 1, the pathophysiology of MI and HF, current treatment strategies, and advances in biomaterial-based cardiovascular therapies were reviewed. In Chapter 2, a platelet membrane-coated nanoparticle system was engineered for targeted delivery of an MCP-1-binding peptide (HSW) to infarcted myocardium following intravenous administration. Neutralization of MCP-1 reduced monocyte recruitment, attenuated inflammatory responses and fibrosis, enhanced cell survival, and improved cardiac function after MI. In Chapter 3, a cardiomyocyte-targeting MG53 fusion protein (CTMG) and vascular endothelial growth factor (VEGF) were co-delivered using a reactive oxygen species-scavenging thermoresponsive hydrogel. The combined treatment provided complementary cardioprotective and pro-angiogenic effects, promoted vascular regeneration, reduced oxidative stress and adverse remodeling, and preserved cardiac function after MI. In Chapter 4, a targeted nanoparticle platform was developed for co-delivery of CTMG and a TGF-β receptor I/II inhibitory peptide (GCG) in a pressure overload-induced HF model. The treatment suppressed fibroblast activation and cardiac fibrosis, mitigated hypertrophy and ventricular dilation, improved tissue repair, and enhanced cardiac function. Collectively, this work demonstrates the potential of targeted biomaterial-based therapeutic platforms to modulate distinct stages of cardiovascular disease progression. By integrating cardiac targeting, sustained delivery, and disease-specific biological interventions, these strategies provide promising approaches for improving cardiac repair after MI and limiting adverse remodeling in HF.

Committee Chair

Jianjun Guan

Committee Members

Jai Rudra; Jie Shen; Mohamed Zayed; Nathaniel Huebsch

Degree

Doctor of Philosophy (PhD)

Author's Department

Interdisciplinary Programs

Author's School

McKelvey School of Engineering

Document Type

Dissertation

Date of Award

8-6-2026

Language

English (en)

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Available for download on Friday, August 04, 2028

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