Metal-organic Frameworks for Controlled Nitric Oxide Delivery and New Therapy

About the project

About the Project Myocardial infarction (MI) remains a leading cause of death worldwide, driven by irreversible cardiomyocyte loss and inadequate vascularization following arterial occlusion. Current clinical interventions, including bypass grafts, stents, and systemic drug therapies, offer only palliative relief and fail to restore lost cardiac function. Cardiac patches, which combine bioactive agents with supportive scaffold materials, represent a promising regenerative strategy. However, existing patch materials suffer from limited mechanical performance, insufficient drug loading capacity, and poor controlled-release behavior. This project addresses these critical gaps by developing novel metal-organic framework (MOF)-based hydrogel cardiac patches capable of localized, sustained nitric oxide (NO) delivery—a key signaling molecule for vasodilation, anti-inflammation, and angiogenesis. This fully funded PhD project will focus on the design, synthesis, and characterization of biocompatible nano-MOFs constructed from essential bio-metal ions (Zn, Fe, Ca, Mg) and amino-acid-derived organic linkers. Specific responsibilities include: Synthesis and Optimization of Nano-MOFs: Using microwave-assisted solvothermal methods with chemical modulators (e.g., benzoic acid, lauric acid) to control crystal nucleation, growth, and morphology. The student will systematically introduce -SH and -NH₂ functional groups to enhance NO chemisorption and introduce unsaturated metal sites to improve stability and binding affinity. NO Loading and Controlled-Release Performance: The student will conduct systematic NO adsorption/desorption experiments under physiological conditions, evaluating adsorption isotherms, diffusion kinetics, cycling stability, and competitive binding with water/phosphate. Saturated MOF samples will be tested for NO release profiles under varying pressure, temperature, and buffer conditions. Integration into MOF-Hydrogel Composites: The selected MOF materials will be incorporated into biocompatible hydrogels (e.g., carrageenan, chitosan) via both direct blending and in-situ growth methods. The student will characterize the mechanical properties, swelling behavior, structural integrity, and NO release kinetics of the resulting cardiac patch prototypes. Advanced Mechanistic Studies: The student will participate in cutting-edge in situ characterization experiments at synchrotron and neutron facilities. Techniques include in situ X-ray/neutron diffraction, inelastic/quasi-elastic neutron scattering, and electron paramagnetic resonance (EPR) spectroscopy to elucidate atomic-level host–guest interactions, NO binding sites, and dynamic release mechanisms. Expected Outcomes and Deliverables: At least 2–3 well-characterized biocompatible MOF materials with high NO loading capacity A prototype MOF-hydrogel cardiac patch with demonstrated mechanical integrity and controlled NO release Mechanistic insights into structure–property relationships guiding future material design Co-authorship on 1–2 high-impact publications and contribution to 1 patent application Training and Development: The student will gain interdisciplinary expertise spanning coordination chemistry, materials engineering, drug delivery, and advanced structural characterization. Regular collaboration with national large-scale facilities will provide unique hands-on experience with state-of-the-art instrumentation. Required Background: Candidates should have a strong foundation in inorganic/materials/ biological chemistry, and a keen interest in biomedical applications. Contact: Sihai.yang@pku.edu.cn Jiangnan.li@pku.edu.cn https://www.chem.pku.edu.cn/sihaiyang/index.htm

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