title: Electrospun Microfiber Scaffolds with Anti-Inflammatory Tributanoylated N-Acetyl-d-Glucosamine Promote Cartilage Regeneration.
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.
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Chaekyu
authors.initials: C
authors.lastname: Kim
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Lucas
authors.initials: L
authors.lastname: Shores
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Qiongyu
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Aly
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Ok Hee
authors.initials: OH
authors.lastname: Jeon
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Do Hun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bernstein
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Rahul
authors.initials: R
authors.lastname: Bhattacharya
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Jemin Jeremy
authors.initials: JJ
authors.lastname: Chae
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Yarema
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Elisseeff
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002073:Butanes / Q000737:chemistry*; D002356:Cartilage / Q000187:drug effects*; D019902:Chondrocytes / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D002073:Butanes; D053583:Interleukin-1beta; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C046888:butane; D000117:Acetylglucosamine