Microglia encapsulation in nanozyme-loaded hydrogels: response to oxidative stress and inflammation

Aim: To investigate the role of hydrogel composition and nanozymes incorporation on the inflammatory response of encapsulated murine microglia. Methods: Sodium alginate (SA) hydrogels containing i) hyaluronic acid (HA) of low-100 kDa or high-1 MDa molecular weight and ii) Mn3O4 nanoparticles (Mn3O4-...

ver descrição completa

Detalhes bibliográficos
Autores: Martín Colomo, Sara, Ontoria Jimenez, Aitor, Tapeinos, Christos, Beloqui Elizazu, Ana, Pineda Martí, José Ramón, Larrañaga Espartero, Aitor
Formato: artículo
Fecha de publicación:2026
País:España
Recursos:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:dnet:addi________::41ee210b68ecf909415ac97b408b768a
Acesso em linha:http://hdl.handle.net/10810/79779
Access Level:acceso abierto
Palavra-chave:Neuroinflammation
microglia
oxidative stress
hydrogels
nanozymes
Descrição
Resumo:Aim: To investigate the role of hydrogel composition and nanozymes incorporation on the inflammatory response of encapsulated murine microglia. Methods: Sodium alginate (SA) hydrogels containing i) hyaluronic acid (HA) of low-100 kDa or high-1 MDa molecular weight and ii) Mn3O4 nanoparticles (Mn3O4-NPs) were prepared and characterized. The inflammatory response of encapsulated microglia was assessed. Results: HA enhanced cell-biomaterial interactions and reduced cell aggregation. Under normal culture conditions, HA induced a pro-inflammatory response, particularly with high-MW HA, with a 7-fold increase in IL-6 expression and a 2.2-fold increase in TNF-α secretion. Under prolonged LPS stimulation, HA promoted an anti-inflammatory shift, with a 2-fold decrease in IL-1β expression and restored IL-4 expression to basal levels. Mn3O4‑NP-loaded hydrogels showed strong H2O2 scavenging capability, protecting cells from oxidative stress. This effect may be partially counterbalanced by •OH generation at high Mn3O4‑NP concentrations. Under short-term LPS stimulation, Mn3O4 promoted a slight pro-inflammatory response, with a 1.3-fold and 1.2-fold increase in IL-1β and TNF-α expression. However, prolonged LPS exposure reflected an anti-inflammatory scenario, with increased IL-4 and a 2.4-fold increase in Arg-1 expression. Conclusion: SA hydrogels are promising carriers for antioxidant nanozymes and microglia, modulating cell response under prolonged inflammation while protecting cells from oxidative stress.