Cunniffe G M, Díaz-Payno P J, Ramey J S, Mahon O R, Dunne A, Thompson E M, O'Brien F J, Kelly D J
Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Dublin 2,
Eur Cell Mater. 2017 Feb 14;33:130-142. doi: 10.22203/eCM.v033a10.
Limitations associated with demineralised bone matrix and other grafting materials have motivated the development of alternative strategies to enhance the repair of large bone defects. The growth plate (GP) of developing limbs contain a plethora of growth factors and matrix cues which contribute to long bone growth, suggesting that biomaterials derived from its extracellular matrix (ECM) may be uniquely suited to promoting bone regeneration. The goal of this study was to generate porous scaffolds from decellularised GP ECM and to evaluate their ability to enhance host mediated bone regeneration following their implantation into critically-sized rat cranial defects. The scaffolds were first assessed by culturing with primary human macrophages, which demonstrated that decellularisation resulted in reduced IL-1β and IL-8 production. In vitro, GP derived scaffolds were found capable of supporting osteogenesis of mesenchymal stem cells via either an intramembranous or an endochondral pathway, demonstrating the intrinsic osteoinductivity of the biomaterial. Furthermore, upon implantation into cranial defects, GP derived scaffolds were observed to accelerate vessel in-growth, mineralisation and de novo bone formation. These results support the use of decellularised GP ECM as a scaffold for large bone defect regeneration.
与脱矿骨基质及其他移植材料相关的局限性促使人们开发替代策略，以增强大骨缺损的修复。发育中肢体的生长板（GP）含有大量有助于长骨生长的生长因子和基质信号，这表明源自其细胞外基质（ECM）的生物材料可能特别适合促进骨再生。本研究的目的是从脱细胞的GP ECM生成多孔支架，并评估其植入到临界尺寸大鼠颅骨缺损后增强宿主介导的骨再生的能力。首先通过与原代人巨噬细胞共培养来评估支架，结果表明脱细胞处理导致IL-1β和IL-8的产生减少。在体外，发现源自GP的支架能够通过膜内或软骨内途径支持间充质干细胞的成骨作用，证明了该生物材料固有的骨诱导性。此外，将其植入颅骨缺损后，观察到源自GP的支架能加速血管长入、矿化和新骨形成。这些结果支持将脱细胞的GP ECM用作大骨缺损再生的支架。
