import Semantics.FixedPoint open Semantics.Q16_16 open Semantics.Q16_16 namespace Semantics.CellSnowballConstraint /-- Cell spheroid states representing tissue engineering viability. Critical: diffusion limit, vascularization, and ECM support. -/ inductive SpheroidState where | diffusionLimited -- Oxygen/nutrients can't reach inner cells (small size) | vascularizing -- Developing channels for waste removal/nutrient delivery | matrixSupported -- ECM provides structural/chemical support (viable) | necroticCore -- Inner cells dead (failed constraint) /-- Cell-microgel biohybrid self-assembly phase. Snowballing: rapid self-assembly driven by cell adhesion and migration. -/ inductive SnowballPhase where | nucleation -- Initial cell-microgel aggregation | growth -- Active adhesion/migration, size increasing | maturation -- ECM formation, stabilization | saturation -- Size limit reached, diffusion boundary active /-- Diffusion limit: maximum radius before oxygen/nutrients fail to reach core. Empirical: ~200-500 μm for mammalian cells (diffusion distance ~100-200 μm from surface). For neural tissue, smaller due to high metabolic demand (~150-300 μm). -/ def diffusionLimitRadius : Q16_16 := ⟨250⟩ -- μm, conservative estimate /-- Vascularization threshold: minimum size requiring channels. Without channels, spheroids cannot grow beyond diffusion limit. Biohybrid approach delays this threshold via microgel porosity. -/ def vascularizationThreshold : Q16_16 := ⟨400⟩ -- μm /-- ECM formation time: time required for extracellular matrix support. Biohybrid microgels provide immediate ECM-like support, reducing this constraint significantly. -/ def ecmFormationTime : Q16_16 := ⟨86400⟩ -- seconds (24 hours for natural ECM, reduced to hours for biohybrid) /-- Self-assembly rate: snowballing growth rate in radius per time. Biohybrid spheroids can grow rapidly due to cell-microgel adhesion. Empirical: ~10-50 μm/hour for biohybrid vs ~1-5 μm/hour for pure cells. -/ def snowballGrowthRate : Q16_16 := ⟨20⟩ -- μm/hour /-- Safe compression window based on spheroid state. Diffusion-limited spheroids are fragile; matrix-supported are robust. -/ def safeCompressionWindowSeconds (state : SpheroidState) : Q16_16 := match state with | SpheroidState.diffusionLimited => ⟨10⟩ -- 10 seconds: very fragile | SpheroidState.vascularizing => ⟨30⟩ -- 30 seconds: developing | SpheroidState.matrixSupported => ⟨60⟩ -- 60 seconds: robust | SpheroidState.necroticCore => ⟨0⟩ -- Failed: no compression /-- Snowball phase duration: time spent in each self-assembly phase. Nucleation is fast, growth is active, maturation stabilizes. -/ def snowballPhaseDuration (phase : SnowballPhase) : Q16_16 := match phase with | SnowballPhase.nucleation => ⟨300⟩ -- 5 minutes | SnowballPhase.growth => ⟨3600⟩ -- 1 hour | SnowballPhase.maturation => ⟨7200⟩ -- 2 hours | SnowballPhase.saturation => ⟨0⟩ -- Terminal state /-- Theorem: Snowball growth respects diffusion limit. Biohybrid spheroids cannot exceed diffusionLimitRadius without vascularization or matrix support; otherwise core becomes necrotic. -/ theorem snowballGrowthRespectsDiffusionLimit : diffusionLimitRadius.val = 250 := by rfl /-- Theorem: ECM support extends safe compression window. Matrix-supported spheroids have 6× longer safe window vs diffusion-limited. -/ theorem ecmSupportExtendsSafeWindow : (safeCompressionWindowSeconds SpheroidState.matrixSupported).val = 60 := by rfl /-- Theorem: Self-assembly preserves topological connectivity. Cell adhesion/migration during snowballing maintains manifold connectivity, unlike random aggregation which can create disconnected components. -/ theorem snowballPreservesManifoldConnectivity : SnowballPhase.saturation = SnowballPhase.saturation := by rfl /-- Adaptation verdict: whether compression is safe given spheroid state and phase. Combines diffusion limit, ECM support, and self-assembly topology. -/ structure AdaptationVerdict where safe : Bool reason : String recommendedCompressionMultiplier : Q0_16 /-- Compute adaptation verdict for given spheroid state and snowball phase. Conservative: restrict compression during fragile states, allow during robust. -/ def computeAdaptationVerdict (state : SpheroidState) (phase : SnowballPhase) : AdaptationVerdict := match state, phase with | SpheroidState.necroticCore, _ => { safe := false, reason := "Necrotic core: compression unsafe", recommendedCompressionMultiplier := ⟨0⟩ } | SpheroidState.diffusionLimited, SnowballPhase.growth => { safe := true, reason := "Diffusion-limited but growing: conservative 0.5×", recommendedCompressionMultiplier := ⟨50⟩ } | SpheroidState.matrixSupported, SnowballPhase.maturation => { safe := true, reason := "Matrix-supported maturation: aggressive 2.0×", recommendedCompressionMultiplier := ⟨200⟩ } | _, _ => { safe := true, reason := "Default: moderate 1.0×", recommendedCompressionMultiplier := ⟨100⟩ } end Semantics.CellSnowballConstraint