Human nail bed extracellular matrix facilitates bone regeneration via macrophage polarization mediated by the JAK2/STAT3 pathway.,Journal of Materials Chemistry B

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Human nail bed extracellular matrix facilitates bone regeneration via macrophage polarization mediated by the JAK2/STAT3 pathway.
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2020-04-03 , DOI: 10.1039/c9tb02910a
Yaling Yu ₁ , Haomin Cui , Cheng Zhang , Demin Zhang , Jun Yin , Gen Wen , Yimin Chai

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Critical-sized bone defects caused by trauma, tumor resection or serious infection represent one of the most challenging problems faced by orthopedic surgeons. However, the construction of bone grafts with good osteointegration and osteoinductivity is a clinical challenge. It has been elaborated that the nail bed tissue is an essential element for digit tip regeneration, suggesting that the nail bed may serve as a new material to manipulate bone regeneration. Herein, it was found that human nail bed extracellular matrix derived from amputated patients stimulates macrophage polarization toward a pro-healing phenotype and the expression of BMP2, to facilitate the osteogenic differentiation of bone marrow stromal cells (BMSCs) in vitro. The in vivo osteogenic capacity of decellularized nail bed scaffolds was then confirmed using a rat model of critical-sized calvarial defects. The in-depth analysis of immune responses to implanted scaffolds revealed that macrophage polarization toward the pro-regenerative M2 phenotype directs osteogenesis, as confirmed by macrophage depletion. A combination of proteomics analysis and RNA interference verified that the JAK2/STAT3 pathway is the positive regulator of macrophage polarization initiated by the decellularized nail bed during the promoted osteogenesis process. Thus, the decellularized human nail bed scaffold developed in this work is a promising biomaterial for bone regeneration.

中文翻译：

人甲床细胞外基质通过由JAK2 / STAT3途径介导的巨噬细胞极化促进骨再生。

由创伤，肿瘤切除或严重感染引起的临界骨缺损是整形外科医生面临的最具挑战性的问题之一。然而，具有良好的骨整合性和骨诱导性的骨移植物的构造是临床挑战。已经详细阐述了指甲床组织是指趾骨再生的必要元素，这表明指甲床可以用作操纵骨再生的新材料。在本文中，发现截肢患者衍生的人指甲床细胞外基质刺激巨噬细胞朝着愈合表型极化和BMP2的表达，以促进体外骨髓基质细胞（BMSCs）的成骨分化。然后使用临界大小的颅骨缺损的大鼠模型确认了脱细胞指甲床支架的体内成骨能力。对植入的支架的免疫反应的深入分析表明，巨噬细胞向着再生前M2型的极化可引导成骨，这已被巨噬细胞耗竭所证实。蛋白质组学分析和RNA干扰的结合证明，JAK2 / STAT3途径是促进成骨过程中脱细胞指甲床引发的巨噬细胞极化的正调节剂。因此，在这项工作中开发的脱细胞的人类指甲床支架是用于骨再生的有前途的生物材料。对植入的支架的免疫反应的深入分析表明，巨噬细胞向着再生型M2表型的极化可引导成骨，这已被巨噬细胞耗竭所证实。蛋白质组学分析和RNA干扰相结合，证明JAK2 / STAT3途径是在促进成骨过程中由脱细胞指甲床引发的巨噬细胞极化的正向调节剂。因此，在这项工作中开发的脱细胞的人类指甲床支架是用于骨再生的有前途的生物材料。对植入的支架的免疫反应的深入分析表明，巨噬细胞向着再生型M2表型的极化可引导成骨，这已被巨噬细胞耗竭所证实。蛋白质组学分析和RNA干扰相结合，证明JAK2 / STAT3途径是在促进成骨过程中由脱细胞指甲床引发的巨噬细胞极化的正向调节剂。因此，在这项工作中开发的脱细胞的人类指甲床支架是用于骨再生的有前途的生物材料。

更新日期：2020-03-19

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