Injectable Magnetic-Responsive Short-Peptide Supramolecular Hydrogels: Ex Vivo and In Vivo Evaluation Mañas Torres, María del Carmen Gila Vilchez, Cristina Vázquez Pérez, Francisco Jesús Blanco Elices, Cristina Rodríguez, Ismael Ángel Alaminos Mingorance, Miguel Álvarez Cienfuegos Rodríguez, Luis López López, Modesto Torcuato Peptides Hybrid hydrogels Biomaterials Magnetic nanoparticles Self-assembly Tissue engineering Regenerative medicine This study was supported by project FIS2017-85954-R funded by MCIN/AEI/10.13039/501100011033/FEDER "Una manera de hacer Europa", Spain, grants FIS PI20/0317 and ICI19/00024 (BIOCLEFT) (MINECO, Instituto de Salud Carlos III, Spain, cofinanced by FEDER funds, European Union), grant PE-0395-2019 (Consejeri ' a de Salud y Familias, Junta de Andalucia ', Spain), and project PPJIB2020.07 (Universidad de Granada, Spain). M.C.M.-T. acknowledges grant PRE2018-083773 funded by MCIN/AEI/10.13039/501100011033 and FSE "El FSE invierte en tu futuro", Spain. C.G.-V. acknowledges grant FPU17/00491 funded by MCIN/AEI/10.13039/501100011033 and FSE "El FSE invierte en tu futuro", Spain. P.K., D.M., and J.-C.S. acknowledge the French Agence Nationale de la Recherche, Project Future Investments UCA JEDI no. ANR-15-IDEX-01 (project RheoGels) for financial support. Funding for open access charge: Universidad de Granada/CBUA. The inclusion of magnetic nanoparticles (MNP) in a hydrogel matrix to produce magnetic hydrogels has broadened the scope of these materials in biomedical research. Embedded MNP offer the possibility to modulate the physical properties of the hydrogel remotely and on demand by applying an external magnetic field. Moreover, they enable permanent changes in the mechanical properties of the hydrogel, as well as alterations in the micro- and macroporosity of its threedimensional (3D) structure, with the associated potential to induce anisotropy. In this work, the behavior of biocompatible and biodegradable hydrogels made with Fmoc-diphenylalanine (Fmoc-FF) (Fmoc = fluorenylmethoxycarbonyl) and Fmoc−arginine−glycine− aspartic acid (Fmoc-RGD) short peptides to which MNP were incorporated was studied in detail with physicochemical, mechanical, and biological methods. The resulting hybrid hydrogels showed enhance mechanical properties and withstood injection without phase disruption. In mice, the hydrogels showed faster and improved self-healing properties compared to their nonmagnetic counterparts. Thanks to these superior physical properties and stability during culture, they can be used as 3D scaffolds for cell growth. Additionally, magnetic short-peptide hydrogels showed good biocompatibility and the absence of toxicity, which together with their enhanced mechanical stability and excellent injectability make them ideal biomaterials for in vivo biomedical applications with minimally invasive surgery. This study presents a new approach to improving the physical and mechanical properties of supramolecular hydrogels by incorporating MNP, which confer structural reinforcement and stability, remote actuation by magnetic fields, and better injectability. Our approach is a potential catalyst for expanding the biomedical applications of supramolecular short-peptide hydrogels. 2021-11-29T07:56:47Z 2021-11-29T07:56:47Z 2021-10-14 info:eu-repo/semantics/article ACS Appl. Mater. Interfaces 2021, 13, 49692−49704. [https://doi.org/10.1021/acsami.1c13972] http://hdl.handle.net/10481/71798 10.1021/acsami.1c13972 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España American Chemical Society