| Autor: |
Catori DM; Institute of Chemistry, University of Campinas, UNICAMP, Campinas 13083-970, São Paulo, Brazil., da Silva LCE; Institute of Chemistry, University of Campinas, UNICAMP, Campinas 13083-970, São Paulo, Brazil., de Oliveira MF; Institute of Chemistry, University of Campinas, UNICAMP, Campinas 13083-970, São Paulo, Brazil., Nguyen GH; School of Chemical, Materials and Biomedical Engineering, College of Engineering, University of Georgia, Athens 30602, Georgia, United States., Moses JC; School of Chemical, Materials and Biomedical Engineering, College of Engineering, University of Georgia, Athens 30602, Georgia, United States., Brisbois EJ; School of Chemical, Materials and Biomedical Engineering, College of Engineering, University of Georgia, Athens 30602, Georgia, United States., Handa H; School of Chemical, Materials and Biomedical Engineering, College of Engineering, University of Georgia, Athens 30602, Georgia, United States.; Pharmaceutical and Biomedical Sciences Department, College of Pharmacy, University of Georgia, Athens 30602, Georgia, United States., de Oliveira MG; Institute of Chemistry, University of Campinas, UNICAMP, Campinas 13083-970, São Paulo, Brazil. |
| Abstrakt: |
An increasing number of studies have shown that the local release of nitric oxide (NO) from hydrogels stimulates tissue regeneration by modulating cell proliferation, angiogenesis, and inflammation. The potential biomedical uses of NO-releasing hydrogels can be expanded by enabling their application in a fluid state, followed by controlled gelation triggered by an external factor. In this study, we engineered a hydrogel composed of methacrylated hyaluronic acid (HAGMA) and thiolated gelatin (GELSH) with the capacity for in situ photo-cross-linking, coupled with localized NO release. To ensure a gradual and sustained NO release, we charged the hydrogels with poly(l-lactic- co -glycolic acid) (PLGA) nanoparticles functionalized with S -nitrosoglutathione (GSNO), safeguarding SNO group integrity during photo-cross-linking. The formation of thiol-ene bonds via the reaction between GELSH's thiol groups and HAGMA's vinyl groups substantially accelerated gelation (by a factor of 6) and increased the elastic modulus of hydrated hydrogels (by 1.9-2.4 times). HAGMA/GELSH hydrogels consistently released NO over a 14 day duration, with the release of NO depending on the hydrogels' equilibrium swelling degree, determined by the GELSH-to-HAGMA ratio. Biocompatibility assessments confirmed the suitability of these hydrogels for biological applications as they display low cytotoxicity and stimulated fibroblast adhesion and proliferation. In conclusion, in situ photo-cross-linkable HAGMA/GELSH hydrogels, loaded with PLGA-GSNO nanoparticles, present a promising avenue for achieving localized and sustained NO delivery in tissue regeneration applications. |
