Electrospun Microfiber Scaffolds with Anti-Inflammatory Tributanoylated N-Acetyl-d-Glucosamine Promote Cartilage Regeneration

Chaekyu Kim, Lucas Shores, Qiongyu Guo, Ahmed Aly, Ok Hee Jeon, Do Hun Kim, Nicholas Bernstein, Rahul Bhattacharya, Jemin Jeremy Chae, Kevin J. Yarema, Jennifer H. Elisseeff

Research output: Contribution to journalArticlepeer-review

Abstract

Tissue-engineering strategies offer promising tools for repairing cartilage damage; however, these strategies suffer from limitations under pathological conditions. As a model disease for these types of nonideal systems, the inflammatory environment in an osteoarthritic (OA) joint limits the efficacy of engineered therapeutics by disrupting joint homeostasis and reducing its capacity for regeneration. In this work, we investigated a sugar-based drug candidate, a tributanoylated N-acetyl-d-glucosamine analogue, called 3,4,6-O-Bu3GlcNAc, that is known to reduce nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in osteoarthritis. 3,4,6-O-Bu3GlcNAc not only inhibited NFκB signaling but also exerted chondrogenic and anti-inflammatory effects on chondrocytes isolated from patients with osteoarthritis. 3,4,6-O-Bu3GlcNAc also increased the expression of extracellular matrix proteins and induced cartilage tissue production in three-dimensional in vitro hydrogel culture systems. To translate these chondrogenic and anti-inflammatory properties to tissue regeneration in osteoarthritis, we implanted 3,4,6-O-Bu3GlcNAc-loaded poly(lactic-co-glycolic acid) microfiber scaffolds into rats. The drug-laden scaffolds were biocompatible, and when seeded with human OA chondrocytes, similarly promoted cartilage tissue formation. 3,4,6-O-Bu3GlcNAc combined with the appropriate structural environment could be a promising therapeutic approach for osteoarthritis.

Original languageEnglish (US)
Pages (from-to)689-697
Number of pages9
JournalTissue Engineering - Part A
Volume22
Issue number7-8
DOIs
StatePublished - Apr 1 2016

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Fingerprint Dive into the research topics of 'Electrospun Microfiber Scaffolds with Anti-Inflammatory Tributanoylated N-Acetyl-d-Glucosamine Promote Cartilage Regeneration'. Together they form a unique fingerprint.

Cite this