Down-regulating ERK1/2 and SMAD2/3 phosphorylation by physical barrier of celecoxib-loaded electrospun fibrous membranes prevents tendon adhesions

Shichao Jiang, Xin Zhao, Shuai Chen, Guoqing Pan, Jialin Song, Ning He, Fengfeng Li, Wenguo Cui, Cunyi Fan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

50 Citations (Scopus)

Abstract

Peritendinous adhesions, as a major problem in hand surgery, may be due to the proliferation of fibroblasts and excessive collagen synthesis, in which ERK1/2 and SMAD2/3 plays crucial roles. In this study, we hypothesized that the complication progression could be inhibited by down-regulating ERK1/2 and SMAD2/3 phosphorylation of exogenous fibroblasts with celecoxib. Celecoxib was incorporated in poly(l-lactic acid)-polyethylene glycol (PELA) diblock copolymer fibrous membranes via electrospinning. Results of an invitro drug release study showed celecoxib-loaded membrane had excellent continuous drug release capability. It was found that celecoxib-loaded PELA membranes were not favorable for the rabbit fibroblast and tenocyte adhesion and proliferation. In a rabbit tendon repair model, we first identified ERK1/2 and SMAD2/3 phosphorylation as a critical driver of early adhesion formation progression. Celecoxib released from PELA membrane was found to down-regulate ERK1/2 and SMAD2/3 phosphorylation, leading to reduced collagen I and collagen III expression, inflammation reaction, and fibroblast proliferation. Importantly, the celecoxib-loaded PELA membranes successfully prevented tissue adhesion compared with control treatment and unloaded membranes treatment. This approach offers a novel barrier strategy to block tendon adhesion through targeted down-regulating of ERK1/2 and SMAD2/3 phosphorylation directly within peritendinous adhesion tissue.

Original languageEnglish
Pages (from-to)9920-9929
Number of pages10
JournalBiomaterials
Volume35
Issue number37
DOIs
Publication statusPublished - 1 Dec 2014
Externally publishedYes

Keywords

  • Celecoxib
  • Electrospun fiber
  • ERK
  • Phosphorylation
  • SMAD
  • Tendon adhesions

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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