Carboxylated gelatin-based instant dissolvable microneedles with robust mechanical properties and biomolecule stabilization for biomedical applications

Gelatin dissolvable microneedle (DMN) patches offer a promising, painless, and rapid transdermal delivery platform. However, conventional DMNs with <5% w/v gelatin exhibit poor mechanical strength and storage stability of biomolecules, while higher concentrations (>5% w/v) hinder dissolvability due to gelation. To address this, we introduced a tailored number of carboxylic groups into the gelatin backbone, generating Modified Gelatin (MG) with improved solubility and reduced viscosity by limiting intra- and intermolecular interactions. MG-DMNs fabricated from MG at a concentration of 10%-20% w/v and ≥5% w/v stabilizing molecules (<i>e.g.</i>, trehalose) exhibited rapid dissolution (5 minutes), high mechanical strength (>95 N per patch), and excellent storage stability. Notably, MG-DMNs retained >80% of platelet-rich plasma (PRP) activity after one month of storage at 4 °C and 25 °C, and ∼60% at 40 °C under 75% relative humidity, as confirmed through an <i>in vitro</i> bioassay, an <i>in ovo</i> CAM assay, and <i>in vivo</i> diabetic wound healing studies. MG-DMNs enable the cold-chain-free and stable delivery of biomolecules for biomedical applications.