Rieber Julia, Niederhauser Roger Khalid, Giovanoli Pietro, Buschmann Johanna
Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Sternwartstrasse 14, 8091 Zurich, Switzerland.
Materials (Basel). 2025 Feb 3;18(3):665. doi: 10.3390/ma18030665.
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.
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.
While the proliferation of rbTenocytes and rbACS was not affected by TIMP-1 supplementation in vitro, the gene expression of was increased in rbTenocytes, the gene expression of was increased in both cell types, the gene expression of was increased in both cell types at 100 ng/mL TIMP-1, and alkaline phosphatase expression 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.
TIMP-1/DP tubes may be used to modulate the fibrotic tissue reaction when applied around conventionally sutured tendon ruptures.
肌腱断裂修复可能是由于重塑过程中细胞外基质(ECM)沉积失衡导致纤维化瘢痕形成。基质金属蛋白酶组织抑制剂(TIMPs)不仅会减少由基质金属蛋白酶(MMPs)调节的ECM降解,还会限制转化生长因子-β1(TGF-β1)的激活,从而减轻纤维化。
在不同浓度的TIMP-1条件下培养兔肌腱细胞(rbTenocytes)和兔脂肪来源干细胞(rbASCs)。评估细胞增殖和基因表达。将TIMP-1掺入乳液静电纺丝的DegraPol(DP)管中,通过扫描电子显微镜(SEM)对其纤维厚度、孔径和壁厚进行表征。测定静态和动态水接触角、傅里叶变换红外光谱(FTIR)以及TIMP-1释放动力学。
虽然在体外添加TIMP-1不影响rbTenocytes和rbACS的增殖,但在rbTenocytes中 的基因表达增加,在两种细胞类型中 的基因表达均增加,在100 ng/mL TIMP-1时两种细胞类型中 的基因表达均增加,并且在rbASCs中碱性磷酸酶表达显著升高。静电纺丝的TIMP-1/DP纤维直径约为5μm,孔径约为10μm,网眼厚度约为200μm。TIMP-1/DP网比纯DP网更具亲水性。TIMP-1从网中持续释放长达7天。
当应用于传统缝合的肌腱断裂周围时,TIMP-1/DP管可用于调节纤维化组织反应。