Electrospun Microfiber Scaffolds with Anti-Inflammatory Tributanoylated N-Acetyl-D-Glucosamine Promote Cartilage Regeneration
Electrospun Microfiber Scaffolds with Anti-Inflammatory Tributanoylated N-Acetyl-D-Glucosamine Promote Cartilage Regeneration
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DOI：
10.1089/ten.tea.2015.0469
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发表时间：
2016-04-01
影响因子：
4.1
通讯作者：
Elisseeff, Jennifer H.
中科院分区：
文献类型：
--
作者：
Kim, Chaekyu;Shores, Lucas;Elisseeff, Jennifer H.
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-Bu(3)GlcNAc, that is known to reduce nuclear factor kappa-light-chain-enhancer of activated B cells (NF kappa B) signaling in osteoarthritis. 3,4,6-O-Bu(3)GlcNAc not only inhibited NF kappa B signaling but also exerted chondrogenic and anti-inflammatory effects on chondrocytes isolated from patients with osteoarthritis. 3,4,6-O-Bu(3)GlcNAc 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-Bu(3)GlcNAc-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-Bu(3)GlcNAc combined with the appropriate structural environment could be a promising therapeutic approach for osteoarthritis.
