Hypothetical In Silico Framework for VascuRegen-TP: A Multifunctional Nanocomposite for Targeted Thrombolysis, Vasodilation, and Temporally Controlled Regenerative Therapy in Acute Ischemic Syndromes

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Abstract

This manuscript presents a rigorous hypothetical in silico model for VascuRegen-TP, an innovative nanocomposite designed to address acute ischemic events through integrated thrombolysis, vasodilation, and delayed regenerative repair. VascuRegen-TP incorporates fibrin-specific tenecteplase (tNK) in liposomes, gold nanorods (AuNRs) conjugated with S-nitrosoglutathione (GSNO) for nitric oxide (NO) release, and pH-sensitive exosomes carrying vascular endothelial growth factor (VEGF) and microRNA-126 (miR-126) for delayed release to promote regenerative repair after the acute phase, avoiding exacerbation of early vascular permeability. The model employs precise mathematical derivations, including substrate-inhibited Michaelis-Menten kinetics enhanced by plasmonic effects, immunologically adjusted Hagen-Poiseuille flow equations, and stochastic differential equations for angiogenesis. Plasmonic enhancement is computed using Gans theory, yielding an intensity factor of approximately 1.82 for AuNRs with aspect ratio 3.5 at 800 nm NIR, validated through Python simulation and consistent with literature finite-difference time-domain (FDTD) simulations. Outputs demonstrate 87.7\% fibrin lysis at 12 hours under enhanced conditions versus 62.3\% for free tNK. Sensitivity is assessed via Sobol indices, Bayesian posteriors (mean recanalization probability $p=0.775$, 95\% HDI [0.63, 0.89]), and uncertainty quantification. The framework highlights nanotechnology applications in vascular repair, such as targeted drug delivery and hyperthermia-induced thrombolysis, supported by recent reviews. Falsifiability, biochemical mechanisms, limitations, ethical considerations, and translational roadmap are detailed, establishing this as a foundational, empirically testable paradigm for nanomedicine in cerebrovascular and cardiovascular therapeutics, grounded in established scientific principles and avoiding pseudoscientific claims.

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