Incorporation of the Amniotic Membrane as an Immunomodulatory Design Element in Collagen Scaffolds for Tendon Repair
Incorporation of the Amniotic Membrane as an Immunomodulatory Design Element in Collagen Scaffolds for Tendon Repair
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DOI：
10.1021/acsbiomaterials.8b01154
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发表时间：
2018-12-01
影响因子：
5.8
通讯作者：
Harley, Brendan A. C.
中科院分区：
文献类型：
--
作者：
Hortensius, Rebecca A.;Ebens, Jill H.;Harley, Brendan A. C.
肌腱损伤通常需要手术干预，即使这样，由于疤痕形成和反复失败，结果也很差。生物材料植入物提供了解决多种潜在问题的潜力，这些问题阻碍了肌腱修复的改善。在这里，我们描述了对各向异性胶原糖胺聚糖（CG）支架生物材料组成的修改，加入羊膜（AM）衍生的基质来改变炎症反应，并为改善再生修复建立条件。我们探索了两种AM基质结合的方法来解决与肌腱修复相关的多个问题。在制造过程中，羊膜衍生基质直接掺入支架微观结构中，形成C/AM复合材料。另一种方法是将脱细胞羊膜基质包裹在传统的胶原硫酸软骨素（C/CS）支架上，形成核壳复合材料（C/CS + AM包裹），类似于目前肩袖和跟腱手术中使用的胶原膜包裹，以提高修复的机械强度。在这些材料中培养的人间充质干细胞（MSCs）在应对白细胞介素1 β和肿瘤坏死因子a的炎症介质挑战时的代谢健康和免疫调节基因表达进行了评估。在7天的培养过程中，支架能够在所有培养基条件下保持MSC的代谢活性。在含有AM的支架中，编码促炎性细胞因子的基因表达下调，这表明AM修饰的CG支架有潜力用于肌腱修复应用。
Tendon injuries often require surgical intervention and even then result in poor outcomes due to scar formation and repeated failure. Biomaterial implants offer the potential to address multiple underlying concerns preventing improved tendon repair. Here, we describe modifications to the composition of an anisotropic collagen glycosaminoglycan (CG) scaffold biomaterial, incorporating amniotic membrane (AM)-derived matrix to alter the inflammatory response and establish conditions for improved regenerative repair. We explored two methods of AM matrix incorporation to address multiple concerns associated with tendon repair. Amniotic membrane -derived matrix was incorporated directly into the scaffold microstructure during fabrication to form a C/AM composite. Alternatively, decellularized amniotic matrix was wrapped around the traditional collagen chondroitin sulfate (C/CS) scaffold to form a core shell composite (C/CS plus AM wrap) in a manner similar to current collagen membrane wraps used in rotator cuff and Achilles tendon surgeries to improve the mechanical strength of the repair. Human mesenchymal stem cells (MSCs) cultured within these materials were evaluated for metabolic health and immunomodulatory gene expression in response to inflammatory media challenge of interleukin 1 beta and tumor necrosis factor a. The scaffolds were able to maintain MSC metabolic activity in all media conditions over the course of a 7 day culture. Expression of genes encoding for pro -inflammatory cytokines were down -regulated in AM containing scaffolds, suggesting the potential to employ AM -modified CG scaffolds for tendon-repair applications.