Stem Cell and Exosome Therapy in Wound Healing: Traps, Paradoxes, and Tricks Transforming Paradigms.

Apstrakt

Cell therapies hold great promise for advancing wound healing; however, translating this promise into consistent clinical benefit has proven elusive. Numerous trials have failed to reproduce the robust outcomes suggested by preclinical studies, reflecting a landscape marked by hidden traps. These include the hostile wound microenvironment, the cytotoxicity of antimicrobial dressings, poor retention and engraftment, immune clearance, and the paradoxical risk of fibrosis and scarring. Across these challenges emerge paradoxes that redefine how traps are understood. The Scarring Paradox reveals that MSCs and EVs may either suppress or reinforce fibrosis, depending on the niche context. The Immune Double-Edged Sword captures the duality of clearance and regenerative modulation. These paradoxes illustrate that traps are not static obstacles but dynamic inflection points. Recognition of these paradoxes has inspired tricks: protective biomaterial carriers, preconditioning strategies, engineered exosomes, and combinatorial therapies with anti-fibrotic, neuromodulatory, or microbiome-targeted adjuncts. Case studies illustrate how classical traps manifest in clinical practice and how paradoxes guide innovation. Emerging adjuncts, ranging from herbal bioactives and bioelectric modulation to circadian synchronization and digital twins, point toward more unconventional but increasingly plausible frameworks for niche control. This perspective review demonstrates that the future of regenerative wound therapy depends not on avoiding traps but on reframing them through paradoxes and converting them into tricks. Stem cell and exosome therapy is thus moving beyond a linear "promise versus failure" narrative toward a systemic, context-aware, programmable approach in which paradoxes drive conceptual renewal and transformative paradigms in wound care.

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