Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, Prince Consort Road, London, SW7 2AZ, United Kingdom.
H. H. Wills Physics Laboratory, University of Bristol, Tyndall Avenue, Bristol, BS8 1TL, United Kingdom.
Biomaterials. 2018 Sep;176:24-33. doi: 10.1016/j.biomaterials.2018.05.029. Epub 2018 May 21.
In developmental biology, gradients of bioactive signals direct the formation of structural transitions in tissue that are key to physiological function. Failure to reproduce these native features in an in vitro setting can severely limit the success of bioengineered tissue constructs. In this report, we introduce a facile and rapid platform that uses magnetic field alignment of glycosylated superparamagnetic iron oxide nanoparticles, pre-loaded with growth factors, to pattern biochemical gradients into a range of biomaterial systems. Gradients of bone morphogenetic protein 2 in agarose hydrogels were used to spatially direct the osteogenesis of human mesenchymal stem cells and generate robust osteochondral tissue constructs exhibiting a clear mineral transition from bone to cartilage. Interestingly, the smooth gradients in growth factor concentration gave rise to biologically-relevant, emergent structural features, including a tidemark transition demarcating mineralized and non-mineralized tissue and an osteochondral interface rich in hypertrophic chondrocytes. This platform technology offers great versatility and provides an exciting new opportunity for overcoming a range of interfacial tissue engineering challenges.
在发育生物学中，生物活性信号的梯度指导组织中结构转变的形成，这对生理功能至关重要。如果在体外环境中无法复制这些天然特征，生物工程组织构建的成功率将受到严重限制。在本报告中，我们介绍了一种简便、快速的平台，该平台使用带有生长因子的糖基超顺磁性氧化铁纳米粒子的磁场定向排列，将生物化学梯度图案化到一系列生物材料系统中。琼脂糖水凝胶中的骨形态发生蛋白 2 梯度用于空间引导人骨髓间充质干细胞的成骨作用，并生成具有明显从骨到软骨的矿物转变的强健的骨软骨组织构建体。有趣的是，生长因子浓度的平滑梯度产生了具有生物学相关性的新兴结构特征，包括分界矿化和非矿化组织的矿化前沿过渡以及富含肥大软骨细胞的骨软骨界面。该平台技术具有很大的通用性，并为克服一系列界面组织工程挑战提供了令人兴奋的新机会。
