Multi-scale design of advanced biomaterials

This thesis details the rational design and validation of innovative biomaterials for therapeutic applications by integrating multi-scale methodologies across three systems: zinc oxide (ZnO) nanoparticles, flexible metal-organic frameworks (MOFs), and bioartificial scaffolds for myocardial tissue engineering. Initial computational investigations using Density Functional Theory (DFT) and reactive molecular dynamics (ReaxFF) predicted the assembly, drug-release, and degradation pathways of functionalized ZnO nanocarriers. These insights enabled the successful synthesis of carriers with validated efficacy in multiple myeloma cell lines. Further simulations elucidated the “gate-opening” diffusion mechanism in the F4_MIL-140A (Ce) framework and provided atomic-level interpretations of NMR relaxometry data for water interactions in MIL-101(Cr). The research culminated in the development of a multifunctional cardiac patch. This scaffold demonstrated biomimetic mechanical properties and therapeutic efficacy in a preclinical rat model of ischemia/reperfusion, highlighting the role of a self-assembling peptide in providing electroconductivity and structural stability. By utilizing complementary techniques, this work reduces empiricism in material design and moves cardiac patch technology toward commercialization via the spin-off Impavid, establishing a clear pathway from laboratory concept to preclinical proof-of-concept.