From Biomaterials to Biological State Engineering: Reframing Advanced Wound Dressings as Adaptive Therapeutic...

Chronic wounds remain a major global health challenge despite substantial advances in biomaterials, regenerative medicine, and wound-care technologies. Current therapeutic strategies are largely based on the assumption that chronic wounds represent impaired or incomplete healing responses and therefore require augmentation of regenerative processes. This paradigm has driven the development of increasingly sophisticated wound dressings incorporating extracellular matrix analogs, growth factors, stem cells, extracellular vesicles, biosensors, and bioelectronic components. However, the clinical impact of these innovations has often fallen short of expectations. In this review, we propose a conceptual framework intended to generate experimentally testable hypotheses rather than provide a definitive mechanistic model. Persistent alterations in immune, stromal, vascular, extracellular matrix, metabolic, mechanical, and microbial networks create interconnected feedback systems that resist transition toward regeneration. From this perspective, successful therapy requires not only stimulation of repair mechanisms but also disruption of the processes that stabilize chronicity. We discuss how advances in systems biology, immunomodulatory biomaterials, bioelectronics, artificial intelligence, and precision medicine support the emergence of adaptive therapeutic interfaces capable of sensing, interpreting, and reprogramming pathological tissue behavior. Unlike previous reviews that primarily summarize emerging wound dressings or regenerative biomaterials, this Review proposes a systems-level conceptual framework in which chronic wounds are interpreted as stable pathological tissue states maintained by multiscale biological memory. This perspective integrates biomaterials, systems biology, artificial intelligence, and tissue-state dynamics into a unified translational model that has not previously been presented in the wound-healing literature. Previous reviews have predominantly focused on the design, biological activity, or clinical performance of individual biomaterials. In contrast, the present Review proposes a systems-level framework that integrates wound biology, biological memory, tissue-state dynamics, artificial intelligence, and adaptive biomaterials into a unified conceptual model for precision wound medicine. This state-based model reframes advanced wound dressings as tools for biological state engineering and provides a translational framework for the future of chronic wound management.