Simultaneous Uterine Replacement Protocol (SURP): A Computational Framework for Biomimetic Developmental Engineering in Ischemic Brain Repair. A Theoretical and In Silico Feasibility Study

Chronic ischemic brain injury is characterized by an adult microenvironment that actively resists axonal regeneration, principally through chondroitin-sulfate-proteoglycan (CSPG)-rich glial scarring and perineuronal net consolidation. We propose the Simultaneous Uterine Replacement Protocol (SURP), a theoretical bio-engineering framework that recapitulates selected features of the embryonic extracellular-matrix (ECM) niche within the infarcted region, coordinated through a "simultaneous replacement" constraint in which glial-scar degradation (k_deg) is matched to neo-scaffold polymerization (k_poly) to respect intracranial volume and pressure homeostasis. The framework centers on a proposed "Master Map Molecule" (M3), a heparan-sulfate-proteoglycan (HSPG) construct with a hypothesized sulfation code for axon guidance, combined with enzymatic scar-clearing agents, morphogen-based differentiation triggers, and adhesion-stabilizing glycans. We formalize the biomechanical constraints with a poroelastic pressure model and the guidance dynamics with a stochastic reaction-diffusion/Langevin framework, characterized in silico using a fully reproducible one-dimensional stochastic simulation. Dimensional analysis of the guidance equations shows that reliable chemotaxis requires a physically dimensioned chemotactic-mobility coefficient, χ_eff, coupling the concentration gradient to a guidance velocity; an unscaled sensitivity parameter instead yields dynamics indistinguishable from undirected diffusion. Sweeping χ_eff by direct simulation identifies the calibration threshold (χ_eff ≈ 1000 μm²·L·s⁻¹·μmol⁻¹) at which guided transport reliably dominates stochastic noise: at this value, 99.0% of simulated growth cones reach within 60 μm of the target source, and 91.3% show net displacement exceeding half the scar-to-target distance, compared to chance-level performance (approximately 50%) without calibration. We present this not as evidence that SURP's guidance mechanism functions in tissue, since no such claim is warranted from a reduced-order simulation, but as a specific, falsifiable, and actionable engineering specification: M3's sulfation-dependent signal amplification must achieve a chemotactic mobility of this order for the proposed guidance mechanism to succeed, a quantity directly measurable in vitro using established growth-cone turning assays. We present this calibration alongside an independent risk assessment and an explicit falsifiability and experimental-validation roadmap that positions the calibrated threshold as the primary near-term falsifiable prediction of the model.