Fabrication and Characterization of Electrospun DegraPol® Tubes Releasing TIMP-1 Protein to Modulate Tendon Healing

电纺 DegraPol® 管的制造和特性分析,释放 TIMP-1 蛋白来调节肌腱愈合

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作者:Julia Rieber, Roger Khalid Niederhauser, Pietro Giovanoli, Johanna Buschmann

Background

Tendon rupture repair can result from fibrotic scar formation through imbalanced ECM deposition during remodeling. The tissue inhibitors of matrix metalloprotease (TIMPs) not only decrease ECM degradation, regulated by matrix metalloproteases (MMPs), but also restrict TGF-β1 activation and thus diminish fibrosis.

Conclusions

TIMP-1/DP tubes may be used to modulate the fibrotic tissue reaction when applied around conventionally sutured tendon ruptures.

Methods

Rabbit tenocytes (rbTenocytes) and rabbit adipose-derived stem cells (rbASCs) were cultivated under different TIMP-1 concentrations. Proliferation and gene expression were assessed. TIMP-1 was incorporated into emulsion electrospun DegraPol® (DP) tubes that were characterized by SEM for fiber thickness, pore size, and wall thickness. Static and dynamic water contact angles, FTIR spectra, and TIMP-1 release kinetics were determined.

Results

While the proliferation of rbTenocytes and rbACS was not affected by TIMP-1 supplementation in vitro, the gene expression of Col1A1 was increased in rbTenocytes, the gene expression of ki67 was increased in both cell types, the gene expression of tenomodulin was increased in both cell types at 100 ng/mL TIMP-1, and alkaline phosphatase expression ALP rose significantly in rbASCs. Electrospun TIMP-1/DP fibers had a ~5 μm diameter, a ~10 μm pore size, and a mesh thickness of ~200 μm. TIMP-1/DP meshes were more hydrophilic than pure DP meshes. TIMP-1 was released from the meshes with a sustained release of up to 7 days. Conclusions: TIMP-1/DP tubes may be used to modulate the fibrotic tissue reaction when applied around conventionally sutured tendon ruptures.

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