White paper on a permissive-signalling framework for possible human limb regeneration studies. This paper argues that the dominant paradigm of instructive signalling — micromanaging each molecular step — is not only unnecessary but potentially counterproductive. We propose a permissive-signalling framework in which a minimal set of environmental conditions is established in the stump, enabling the system's endogenous logic to self-organise. The synthesis integrates twelve biological mechanisms (published between 2013 and 2026) under four permissive pillars — chromatin, metabolic, bioelectric, mechanical — with a thirteenth entry providing an ex vivo validation platform (limb-bud organoids) as a gating step before animal work. We describe a hypothetical convergence protocol that extends the Murugan/Levin 2022 adult Xenopus protocol into a mammalian context, and identify the specific experimental gap — a large-mammal (porcine) bridge experiment — that would translate this framework into a testable clinical pathway. Author: Alejandro García Ruiz. Independent researcher, Toledo, Spain.
Alejandro García Ruiz (Sat,) studied this question.