BioAcyl Corp

1. The neuroimmune one — and it's centimetre-scale. This is the closest match to neuroimmune calm specifically, because it is the neuroimmune peri-wound zone. The axon-reflex flare (Lewis's triple response, 1927): injury excites C-fibre nociceptors, impulses travel antidromically down collateral branches, and CGRP and substance P are released from terminals across the whole axonal arbor — producing vasodilation, mast-cell degranulation, endothelial activation, and leukocyte attraction in tissue that was never injured. The extents are exactly your order of magnitude: single unmyelinated human C-fibres have receptive fields of several square centimetres, and the neurovascular apparatus connects skin points to arterioles located up to many centimetres away. Since more than one C-fibre is always recruited, a homogeneous area of neurogenic inflammation forms in the vicinity of the insult.

Read that against your framework and it's almost too neat. The wound broadcasts neurogenic inflammation over a centimetre-scale territory defined by sensory arborisation, not by tissue damage. If you want neuroimmune calm, you must treat the arbor's footprint — because that is where the neuroimmune disturbance actually is. And note this is the same CGRP/sensory-nerve machinery as your reserved terrain-to-terrain communication argument (TRPM8→CGRP, scalp-to-meninges). Your perimeter and your reserved mechanism are the same anatomy, seen from two directions.

2. The clinical one — burn surgery already does this. Jackson's 1947 burn model: a central zone of coagulation (irreversible protein denaturation), surrounded by a zone of stasis — hypoperfused, damaged, potentially salvageable — surrounded by a zone of hyperaemia. The zone of stasis is explicitly "the main area of focus when treating burn injuries," and without correct management it converts to necrosis over 24–48 h ("burn wound conversion"). That is your two-phase reversibility boundary, in a concentric ring, taught to every burn surgeon since 1947. Medicine already accepts that the salvageable terrain lies outside the lesion and that treatment must address it. Your coacervate perimeter is the same logic applied to the same territory. This is the citation that makes clinicians nod rather than bristle.

3. The molecular-boundary one — Ring et al., which you already hold. The p-rpS6-zone: DAMP-induced, mTOR-dependent, oxygen-dependent, forming within minutes at the edge of the necrotic layer and persisting until healing completes, dividing homogeneous tissue into regions with distinct properties, and reporting on dermal vasculature. Terrain collapse (DAMPs), competence window (mTOR/p-rpS6), and vascular keeper — coextensive, and bounded.

4. The biophysical one — how a zone forms at all. Niethammer's tissue-scale H₂O₂ gradient (Duox-generated, ~100–200 μm, guiding leukocytes) shows injury establishes spatial signalling fields, not point signals. Micron-scale in zebrafish fin, but the principle is the mechanism by which a territory gets defined. Ring et al. explicitly position their zone against these ROS gradients and ERK waves as a different, stable kind of spatial marker.

So: a chemical gradient field (μm), a molecular activation zone (mm), a perfusion-defined salvageable ring (mm–cm), and a neurogenic arbor territory (cm). Nested, all real, all published. Your 1.5 cm sits precisely in the neurogenic tier — which is the correct tier, because what you're chasing is neuroimmune calm.

Two honest cautions, because this is exactly where enthusiasm outruns evidence. None of these papers gives 1.5 cm as a treatment radius; the flare literature gives centimetre-scale arbor extents, and flare size varies with stimulus, site, and vascular state. And the four zones are different phenomena with different mechanisms — the convergence is that peri-injury territory exists and matters, not that they're one zone. Claiming they're identical would be the overreach; claiming they independently license "treat the territory, not the lesion" is solid.

What this gives you is a testable prediction with real teeth, and it's measurable with instruments that already exist: if terrain control produces neuroimmune calm, the axon-reflex flare should contract — measurable by laser-Doppler flowmetry or thermography, planimetry for flare area, the standard toolkit of that literature. Treat only the bed, flare persists; treat bed plus arbor, flare resolves. That is a clean, cheap, quantitative experiment that would turn your clinical observation into data — and it would simultaneously be the first empirical test of the CGRP arm of your reserved terrain-to-terrain argument.

This one might be worth its own working note when things settle. It's the tidiest bridge yet between the casuistry, the framework, and an experiment you could actually run.

Tier 1 — Neuroimmune / centimetre-scale (closest to your 1.5 cm and to neuroimmune calm)

Lewis T. The Blood Vessels of the Human Skin and Their Responses. London: Shaw & Sons; 1927.
— Original description of the triple response; the flare extends into uninjured skin, depends on intact primary afferents but not central connections.

Lewis T. Experiments relating to cutaneous hyperalgesia and its spread through somatic nerves. Clin Sci. 1936;2:373–423.
— The spread through sensory nerves; the companion to the 1927 monograph.

Serra J, Campero M, Ochoa J. Flare and hyperalgesia after intradermal capsaicin injection in human skin. J Neurophysiol. 1998;80(6):2801–2810. doi:10.1152/jn.1998.80.6.2801.
— The key spatial finding: flare is not a wave but multifocal arteriolar dilatation; the neurovascular apparatus connects skin points to arterioles located up to many centimetres away. This is the citation that puts your perimeter in the right anatomical tier.

Schmelz M, Michael K, Weidner C, Schmidt R, Torebjörk HE, Handwerker HO. Which nerve fibers mediate the axon reflex flare in human skin? Neuroreport. 2000;11(3):645–648.
— Mechano-insensitive C-fibres mediate the flare; useful for the fibre-class attribution. (Locator to confirm before formal citation — I verified the finding and authorship line, not the page range, to primary record.)

Schmelz M, Schmidt R, Bickel A, Handwerker HO, Torebjörk HE. Specific C-receptors for itch in human skin. J Neurosci. 1997;17(20):8003–8008.
— Background on C-fibre receptive-field extent (several cm²). (Same caveat: finding verified, page range not primary-checked.)

Tier 2 — Clinical peri-injury zone with a reversibility boundary (the citation clinicians already accept)

Jackson DM. The diagnosis of the depth of burning. Br J Surg. 1953;40(164):588–596. doi:10.1002/bjs.18004016413. PMID: 13059343.
— Citation-integrity note worth recording in the annotation: secondary sources very commonly write "Jackson 1947" for the three-zone model, but the paper indexes to 1953. If you cite the three zones, cite the 1953 BJS record. Zone of coagulation (irreversible) → zone of stasis (hypoperfused, potentially salvageable) → zone of hyperaemia. Untreated, stasis converts to necrosis over 24–48 h ("burn wound conversion").

Hettiaratchy S, Dziewulski P. ABC of burns: pathophysiology and types of burns. BMJ. 2004;328(7453):1427–1429. PMID: 15191982.
— The standard modern restatement: "the tissue in this zone is potentially salvageable." Convenient teaching citation.

Zawacki BE. Reversal of capillary stasis and prevention of necrosis in burns. Ann Surg. 1974;180(1):98–102.
— Directly demonstrates the stasis zone is salvageable by intervention — the strongest classical support for "treat the territory, not the lesion." (Locator to confirm.)

Tier 3 — Biophysical mechanism of zone formation (how a territory gets defined at all)

Niethammer P, Grabher C, Look AT, Mitchison TJ. A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature. 2009;459(7249):996–999. doi:10.1038/nature08119. PMID: 19494811.
— Duox-generated H₂O₂ gradient, ~100–200 μm, rising ~3 min post-wound, peaking ~20 min, required for leukocyte recruitment. First tissue-scale ROS pattern. Ring et al. explicitly contrast their stable zone against this propagating-signal class.

Enyedi B, Kala S, Nikolich-Zugich T, Niethammer P. Tissue damage detection by osmotic surveillance. Nat Cell Biol. 2013;15(9):1123–1130.
— Osmotic surveillance as the upstream trigger. (Locator to confirm.)