Choi, Youngjin Park, Su Jeong Cho, Bo Kyung Lee, Jongmin Sung, Yejin Zeng, Yang C. Choi, Nakwon Shih, William M. Kim, Soo Hyun Kim, Dong-Hwee Cho, Seung-Woo Jung, Youngmee Ryu, Ju Hee 2025-11-17T02:37:34Z 2025-11-17T02:37:34Z 2025-11-11 2025-10 1530-6984 https://pubs.kist.re.kr/handle/201004/153500 Severe peripheral nerve injuries cause significant functional impairments due to limited regenerative capacity. Growth factors such as brain-derived neurotrophic factor (BDNF) and nerve growth factor promote neuronal differentiation and regeneration, but their controlled and efficient delivery remains challenging. Here, we present square block DNA nanostructures (SQBs) as a modular platform for the spatially controlled presentation of growth-factor-mimicking peptides. SQBs displaying 38 BDNF-mimicking peptides at 5 nm intervals enhanced the neuronal differentiation of human mesenchymal stem cells. Dual-ligand presentation was validated using fluorescein isothiocyanate and cyanine5.5, demonstrating ratio-controlled conjugation and colocalized delivery within single cells. In a sciatic nerve injury model, BDNF-functionalized SQBs modestly improved functional recovery, reduced muscle atrophy, and enhanced remyelination compared to the untreated crush group. Histological analysis revealed increased myelin sheath thickness and improved axonal integrity. These findings underscore potential SQBs as programmable and spatially precise delivery systems for neuroregenerative therapies and broader tissue repair strategies. English American Chemical Society DNA Nanostructures for Modular Growth Factor Delivery and Peripheral Nerve Repair Article 10.1021/acs.nanolett.5c03151 1 Nano Letters, v.25, no.41, pp.14859 - 14871 Nano Letters 25 41 14859 14871 N scie scopus 001585991300001 2-s2.0-105018712966 Chemistry, Multidisciplinary Chemistry, Physical Nanoscience & Nanotechnology Materials Science, Multidisciplinary Physics, Applied Physics, Condensed Matter Chemistry Science & Technology - Other Topics Materials Science Physics Article MESENCHYMAL STEM-CELLS NEUROTROPHIC FACTOR STROMAL CELLS NEUROGENESIS DIFFERENTIATION TRANSPLANTATION MIGRATION DNA nanostructures growth-factor-mimicking peptide modular platform peripheral nerve repair dual-ligand codelivery