Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
J Mater Chem B. 2020 May 14;8(18):4067-4079. doi: 10.1039/c9tb02910a. Epub 2020 Apr 3.
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.
创伤、肿瘤切除或严重感染导致的临界尺寸骨缺损是骨科医生面临的最具挑战性的问题之一。然而，构建具有良好骨整合性和骨诱导性的骨移植物是临床面临的挑战。有研究详细阐述了钉床组织是指尖再生的重要元素，这表明钉床可能成为操纵骨再生的新材料。在这里，发现从截肢患者中获得的人钉床细胞外基质可刺激巨噬细胞向促进愈合的表型极化，并表达 BMP2，从而促进体外骨髓基质细胞（BMSCs）的成骨分化。然后使用大鼠临界尺寸颅骨缺损模型证实了脱细胞钉床支架的体内成骨能力。对植入支架的免疫反应的深入分析表明，巨噬细胞向促进再生的 M2 表型的极化方向指导成骨，这可以通过巨噬细胞耗竭来证实。蛋白质组学分析和 RNA 干扰的组合验证了在促进成骨过程中，脱细胞钉床启动的 JAK2/STAT3 通路是巨噬细胞极化的正向调节剂。因此，本研究开发的脱细胞人钉床支架是一种有前途的骨再生生物材料。
