Citric acid modification of a polymer exhibits antioxidant and anti-inflammatory properties in stem cells and tissues

J Biomed Mater Res A. 2019 Nov;107(11):2414-2424. doi: 10.1002/jbm.a.36748. Epub 2019 Jun 20.


Biomaterials can be used as carriers of antioxidant or drug to the oxidative injury site of tissue and decrease intracellular oxidative stress levels, however, low dosage delivery or unstable molecular structure of antioxidant or drug limited the long-term sustained release. A chemically stable antioxidant molecule is essential to serve as antioxidant structure components of biomaterials that may provide the relatively high antioxidant content and persisting local antioxidant release with the degradation of materials. In this study, we used citric acid modified polyvinyl alcohol (PVA-C) as a model biomaterial to investigate the role of citric acid on the material stimulated antioxidant and anti-inflammatory effects. In cellular-based assays, PVA-C extracts showed a protective effects on bone marrow mesenchymal stem cells (BMSCs) under oxidative stress. It could enhance the antiapoptotic ability of stem cells by inhibiting reactive oxygen species. Further studies revealed that PVA-C extracts upregulated the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) and superoxide dismutase [Mn] (SOD2). in vivo animal assays, PVA-C extracts showed significant inhibitory effects on the oxidative stress and inflammatory reaction which were induced by lipopolysaccharide (LPS). These findings suggest that the citric acid modified polymer can regulate the redox signaling of stem cells and tissues by the release of citric acid from materials, leading to enhanced oxidative stress-induced degenerative diseases and inflammatory diseases therapy.

Keywords: anti-inflammatory; antioxidant; citric acid; oxidative stress; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents* / chemistry
  • Anti-Inflammatory Agents* / pharmacology
  • Antioxidants* / chemistry
  • Antioxidants* / pharmacology
  • Bone Marrow Cells / metabolism*
  • Citric Acid* / chemistry
  • Citric Acid* / pharmacology
  • Inflammation / metabolism
  • Mesenchymal Stem Cells / metabolism*
  • Oxidative Stress / drug effects
  • Polyvinyl Alcohol* / chemistry
  • Polyvinyl Alcohol* / pharmacology
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism


  • Anti-Inflammatory Agents
  • Antioxidants
  • Reactive Oxygen Species
  • Citric Acid
  • Polyvinyl Alcohol