A biomaterials roadmap from retinoic acid biology to kidney regenerative therapy

The mammalian kidney cannot generate new nephrons after birth, a key driver of chronic kidney disease progression toward end-stage renal disease. Retinoic acid (RA) is an evolutionarily conserved morphogen essential for kidney development, and its signaling is reactivated after injury to coordinate repair-yet this endogenous repair program is transient and insufficient to guide the kidney along the regenerative continuum toward de novo nephron formation. Despite its regenerative potential, RA's clinical translation is limited by systemic toxicity, a narrow therapeutic window, and poor pharmacokinetics. Here, we synthesize evidence from developmental biology and injury models showing that RA can activate endogenous renal progenitor programs. We then analyze its pharmacological and toxicity barriers and introduce a developmental bioinspiration framework using renal-targeted nanocarriers and multifunctional scaffolds to overcome these obstacles. By recapitulating native RA signaling dynamics, these platforms aim to steer the adult kidney away from maladaptive fibrosis and toward functional restoration.