Park, Il-Soo Cho, Younghak Lee, Yen Jea Daniela Gutierrez Zuckermann, Ronald N. Seong, Hyejeong Kim, Jae Hong 2026-02-20T07:00:28Z 2026-02-20T07:00:28Z 2026-02-11 2026-02 1936-0851 https://pubs.kist.re.kr/handle/201004/154345 Supramolecular hydrogels that mimic the extracellular matrix (ECM) represent promising materials for tissue engineering and drug delivery. However, conventional hydrogels formed via the self-assembly of natural or synthetic building blocks often face a trade-off between biological functionality and biochemical stability, limiting their utility in long-term or protease-rich environments. Peptoids, a class of peptide-inspired, sequence-defined polymers, offer a compelling alternative due to their exceptional proteolytic resistance and bioactivity. Despite this potential, the development of supramolecular peptoid hydrogels has been hindered by the absence of backbone hydrogen bond donors, which limits long-range ordering necessary for efficient hydrogel formation. This work describes a short peptoid functionalized at the N-terminus with an octyl chain that readily self-assembles into hydrogels. Hydrophobic interactions among pendant octyl groups promote directional peptoid packing into highly ordered nanosheets, which interconnect to form a porous hydrogel network. These hydrogels exhibit tunable viscoelasticity, shear-thinning, and self-healing properties, enabling their use as inks for extrusion-based 3D printing. They support NIH-3T3 fibroblast adhesion, spreading, and proliferation, maintaining greater than 95% cell viability over 4 days. Moreover, the hydrogels retain their macroscopic integrity under protease-rich conditions, enabling sustained cargo release and uniform cellular uptake. Together, this study demonstrates a class of supramolecular peptoid hydrogelators that integrate biocompatibility, 3D printability, and proteolytic stability, providing a versatile platform for ECM-mimetic scaffolds in regenerative medicine and long-term therapeutic delivery. English American Chemical Society N-Terminal Octylated Peptoid Hydrogels as 3D-Printable Cell Scaffolds and Proteolytically Robust Cargo Depots Article 10.1021/acsnano.5c16998 1 ACS Nano, v.20, no.7, pp.5650 - 5661 ACS Nano 20 7 5650 5661 N scie scopus 001685286300001 Chemistry, Multidisciplinary Chemistry, Physical Nanoscience & Nanotechnology Materials Science, Multidisciplinary Chemistry Science & Technology - Other Topics Materials Science Article; Early Access EXTRACELLULAR-MATRIX PEPTIDE AGGREGATION POLYMERS peptoid hydrogels self-assembly cell scaffolds protease-resistant materials cargodelivery