Background <p>While homeostasis has been defined to date and a common understanding exists of its context and how it responds to stress, there is still a need for a better understanding of how homeostasis is regained and for the boundaries defining the physiological and pathological responses of tissue/microenvironment under stress. A modern adaptability view should improve our understanding of how the prior status (host health) or resilience is reinstated. The living entity, regarded as a superorganism that coexists with a microbiota and participates in the process, not neglecting the role of constitutive innate immunity in providing formidable defenses and access to superior healing with regenerative probabilities ‒if properly elicited, should corroborate its remote origins and early description dating back to 1900, by Adami ^{(cited below)}.</p> Method <p>The method is an integrative collation of the basic science underpinning the new principle of tissue/microenvironmental control, that exploits the opportunities within the cell autonomous response as preference to an adaptive outcome. Both in-depth Literature search and the historical proprietary preclinical and clinical research that led to its establishment are taken into account and explain how over 25 years the improved outcomes of healing were discovered. Finally, how efficacy and safety of the methodology validated prior statistical expectations, allowing its characterization as a standard method for wound healing that gained sanitary registration and translated into a standard intervention for wound healing.</p> Results <p>This new knowledge has translated into forms of inter-polyelectrolyte, hydro, and liposoluble forms of interventions with superior safety, efficacy, much lessened pain awareness, abatement of inflammation, absence of infection, and tissue regeneration when used immediately after injury, and unusual practicality at a very reasonable cost. Furthermore, the evidence compiled in humans from the standard practice of this validated “as-safe” new methodology is concordant with the existence of healing within innate immunity.</p> Conclusion <p>The practicality and efficacy of microenvironment control by inter-polyelectrolyte layers embodying an autacoid, is more inclusive to convey the necessary cues to the interactome (tissue/microenvironment) with the capability of interacting with the constitutive innate immunity frame, rescuing deviations of homeostasis back into the correct path towards thorough resolution, adaptation, and reinstatement of host health by regeneration. Not only a contrasting concept to the universally accepted healing ending in fibrosis, but it is also exemplary of what it takes to intervene disease.</p> Graphical abstract <p></p>