Your browser doesn't support javascript.
loading
Biomaterial-mediated intracellular control of macrophages for cell therapy in pro-inflammatory and pro-fibrotic conditions.
Tylek, Tina; Wong, Joanna; Vaughan, Andrew E; Spiller, Kara L.
Afiliação
  • Tylek T; Drexel University, School of Biomedical Engineering, Science and Health Systems, Philadelphia, PA 19104, USA.
  • Wong J; Department of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA.
  • Vaughan AE; Department of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA.
  • Spiller KL; Drexel University, School of Biomedical Engineering, Science and Health Systems, Philadelphia, PA 19104, USA. Electronic address: kls35@drexel.edu.
Biomaterials ; 308: 122545, 2024 Jul.
Article em En | MEDLINE | ID: mdl-38547831
ABSTRACT
Macrophages are key modulators of all inflammatory diseases and essential for their resolution, making macrophage cell therapy a promising strategy for regenerative medicine. However, since macrophages change rapidly in response to microenvironmental cues, their phenotype must be controlled post-administration. We present a tunable biomaterial-based strategy to control macrophages intracellularly via small molecule-releasing microparticles. Poly(lactic-co-glycolic acid) microparticles encapsulating the anti-inflammatory and anti-fibrotic drug dexamethasone were administered to macrophages in vitro, with uptake rates controlled by different loading regimes. Microparticle dose and dexamethasone content directly affected macrophage phenotype and phagocytic capacity, independent of particle content per cell, leading to an overall pro-reparative, anti-inflammatory, anti-fibrotic phenotype with increased phagocytic and ECM degrading functionality. Intracellularly controlled macrophages partially maintained this phenotype in vivo in a murine pulmonary fibrosis model, with more prominent effects in a pro-fibrotic environment compared to pro-inflammatory. These results suggest that intracellular control using biomaterials has the potential to control macrophage phenotype post-administration, which is essential for successful macrophage cell therapy.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Materiais Biocompatíveis / Dexametasona / Copolímero de Ácido Poliláctico e Ácido Poliglicólico / Macrófagos Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Materiais Biocompatíveis / Dexametasona / Copolímero de Ácido Poliláctico e Ácido Poliglicólico / Macrófagos Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article