Scaffolds Functionalized with Matrix from Induced Pluripotent Stem Cell Fibroblasts for Diabetic Wound Healing.,Advanced Healthcare Materials

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Scaffolds Functionalized with Matrix from Induced Pluripotent Stem Cell Fibroblasts for Diabetic Wound Healing.
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-06-29 , DOI: 10.1002/adhm.202000307
Francesco Santarella ₁ , Rukmani Sridharan ₁ , Milica Marinkovic ₁ , Ronaldo Jose Farias Correa Do Amaral _{1,

2} , Brenton Cavanagh ₁ , Avi Smith ₃ , Olga Kashpur ₃ , Behzad Gerami-Naini ₃ , Jonathan A Garlick ₃ , Fergal J O'Brien _{1,

4,

5} , Cathal J Kearney _{1,

4,

5,

6}

Affiliation

Diabetic foot ulcers (DFUs) are chronic wounds, with 20% of cases resulting in amputation, despite intervention. A recently approved tissue engineering product—a cell‐free collagen‐glycosaminoglycan (GAG) scaffold—demonstrates 50% success, motivating its functionalization with extracellular matrix (ECM). Induced pluripotent stem cell (iPSC) technology reprograms somatic cells into an embryonic‐like state. Recent findings describe how iPSCs‐derived fibroblasts (“post‐iPSF”) are proangiogenic, produce more ECM than their somatic precursors (“pre‐iPSF”), and their ECM has characteristics of foetal ECM (a wound regeneration advantage, as fetuses heal scar‐free). ECM production is 45% higher from post‐iPSF and has favorable components (e.g., Collagen I and III, and fibronectin). Herein, a freeze‐dried scaffold using ECM grown by post‐iPSF cells (Post‐iPSF Coll) is developed and tested vs precursors ECM‐activated scaffolds (Pre‐iPSF Coll). When seeded with healthy or DFU fibroblasts, both ECM‐derived scaffolds have more diverse ECM and more robust immune responses to cues. Post‐iPSF‐Coll had higher GAG, higher cell content, higher Vascular Endothelial Growth Factor (VEGF) in DFUs, and higher Interleukin‐1‐receptor antagonist (IL‐1ra) vs. pre‐iPSF Coll. This work constitutes the first step in exploiting ECM from iPSF for tissue engineering scaffolds.

中文翻译：

用来自诱导性多能干细胞成纤维细胞的基质功能化的支架进行糖尿病伤口愈合。

糖尿病足溃疡（DFU）是慢性伤口，尽管进行了干预，但仍有20％的病例导致截肢。最近批准的组织工程产品-一种无细胞的胶原-糖胺聚糖（GAG）支架-展示了50％的成功，并通过细胞外基质（ECM）促进了其功能化。诱导多能干细胞（iPSC）技术将体细胞重编程为胚胎样状态。最近的发现描述了iPSC衍生的成纤维细胞（“ iPSF后”）是促血管生成的，比其体细胞前体（“ iPSF前”）产生更多的ECM，并且它们的ECM具有胎儿ECM的特征（伤口再生优势，因为胎儿可以治愈）无疤痕）。与iPSF后相比，ECM的产量提高了45％，并且具有有利的成分（例如I型和III型胶原以及纤连蛋白）。在这里与前体ECM激活的支架（Pre-iPSF Coll）相比，使用iPSF后的细胞生长的ECM（Post-iPSF Coll）开发了冻干支架并进行了测试。当用健康或DFU成纤维细胞播种时，两种ECM衍生的支架均具有更多样化的ECM和对提示的更强健的免疫反应。iPSF后Coll与iPSF前Coll相比，DFU中具有更高的GAG，更高的细胞含量，更高的血管内皮生长因子（VEGF）和更高的白介素1受体拮抗剂（IL-1ra）。这项工作是将iPSF的ECM用于组织工程支架的第一步。与iPSF之前相比，DFU中的血管内皮生长因子（VEGF）更高，白介素1受体拮抗剂（IL-1ra）也更高。这项工作是将iPSF的ECM用于组织工程支架的第一步。与iPSF之前相比，DFU中的血管内皮生长因子（VEGF）更高，白介素1受体拮抗剂（IL-1ra）也更高。这项工作是将iPSF的ECM用于组织工程支架的第一步。

更新日期：2020-08-19

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