Nanofibrous Poly(amino acid ester) Dressing for Promoting Diabetic Wound Healing via Spatiotemporal Coordination of Immunomodulation and Tissue Regeneration

Here, we developed an extracellular matrix-mimicking dressing, termed ANM, that modulates arginine utilization within the diabetic wound microenvironment to re-establish the spatiotemporal coordination of healing. ANM was <i>in situ</i> fabricated by hand-held electrospinning using a rationally designed arginine- and norvaline-based poly(ester amide), yielding a conformable and breathable nanofibrous dressing.

Its porous and hydrolyzable structure enabled moisture- and enzyme-responsive degradation, allowing sustained release of arginine- and norvaline-containing degradants. These bioactive degradants cooperatively modulated macrophage phenotypic transitions, initially promoting a timely proinflammatory response, followed by a spontaneous shift toward a pro-reparative state, thereby restoring the temporally sequenced inflammatory program in diabetic wounds.