Nitric oxide-releasing photocrosslinked chitosan cryogels

• Published in: Nitric oxide 2024-05, Vol.146, p.48-57
• Main Authors: Vieira de Almeida, Herllan, Escobar da Silva, Laura Caetano, Ganzarolli de Oliveira, Marcelo
• Format: Article
• Language: English
• Subjects: Chitosan; Cryogel; Photocrosslinking; S-nitrosomercaptosuccinic acid; S-nitrosothioglycolic acid; S-nitrosothiols
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2024.03.006

The highly porous morphology of chitosan cryogels, with submicrometric-sized pore cell walls, provides a large surface area which leads to fast water absorption and elevated swelling degrees. These characteristics are crucial for the applications of nitric oxide (NO) releasing biomaterials, in which the release of NO is triggered by the hydration of the material. In the present study, we report the development of chitosan cryogels (CS) with a porous structure of interconnected cells, with wall thicknesses in the range of 340–881 nm, capable of releasing NO triggered by the rapid hydration process. This property was obtained using an innovative strategy based on the functionalization of CS with two previously synthesized S-nitrosothiols: S-nitrosothioglycolic acid (TGA(SNO)) and S-nitrosomercaptosuccinic acid (MSA(SNO)). For this purpose, CS was previously methacrylated with glycidyl methacrylate and subsequently submitted to photocrosslinking and freeze-drying processes. The photocrosslinked hydrogels thus obtained were then functionalized with TGA(SNO) and MSA(SNO) in reactions mediated by carbodiimide. After functionalization, the hydrogels were frozen and freeze-dried to obtain porous S-nitrosated chitosan cryogels with high swelling capacities. Through chemiluminescence measurements, we demonstrated that CS-TGA(SNO) and CS-MSA(SNO) cryogels spontaneously release NO upon water absorption at rates of 3.34 × 10−2 nmol mg−1 min−1 and 1.27 × 10−1 nmol mg−1 min−1, respectively, opening new perspectives for the use of CS as a platform for localized NO delivery in biomedical applications. [Display omitted] •Chitosan cryogels feature sub-micrometric sized pore cell walls for fast water absorption.•Innovative functionalization with S-nitrosothiol groups enables controlled nitric oxide release.•Chemiluminescence measurements confirm spontaneous NO release from S-nitrosated chitosan cryogels.•Potential applications include localized NO release from bodily fluid absorption.