Abstract

To overcome the limitations of repeated GH injection therapy, gelatin methacryloyl (GelMA)/hyaluronic acid (HA) composite hydrogel microneedles were fabricated for potential non-invasive transdermal delivery of recombinant human growth hormone (rhGH) and long-acting human growth hormone Fc fusion protein (hGH-Fc). All-atom molecular dynamics simulations combined with morphological, mechanical, and scanning electron microscopy (SEM) characterization were applied to screen optimal microneedle formulations, with Fourier transform infrared spectroscopy (FTIR) analysis and Parafilm M penetration tests verifying physicochemical compatibility and insertion capability. MD simulations revealed that rhGH stabilized the matrix via hydrogen bonds and electrostatic interactions, while hGH-Fc bound mainly through van der Waals forces. Through orthogonal screening of GelMA (5%, 10%, 15%) and HA (0.5%, 1%, 2%, 5%), the 10% GelMA with 0.5–2% HA was identified as the optimal range; the representative 10% GelMA/1% HA formulation exhibited a single-tip force exceeding 1.40 N and ~500 μm penetration in Parafilm M. This study offers a theoretical and technical basis for the design and optimization of hydrogel microneedle carriers for short- and long-acting GH delivery.

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