Institute for Biomechanics, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
Biomacromolecules. 2021 Jun 14;22(6):2460-2471. doi: 10.1021/acs.biomac.1c00241. Epub 2021 May 10.
Bone regeneration is a highly complex physiological process regulated by several factors. In particular, bone-mimicking extracellular matrix and available osteogenic growth factors such as bone morphogenetic protein (BMP) have been regarded as key contributors for bone regeneration. In this study, we developed a biomimetic hybrid scaffold (CEGH) with sustained release of BMP-2 that would result in enhanced bone formation. This hybrid scaffold, composed of BMP-2-loaded cryoelectrospun poly(ε-caprolactone) (PCL) (CE) surrounded by a macroporous gelatin/heparin cryogel (GH), is designed to overcome the drawbacks of the relatively weak mechanical properties of cryogels and poor biocompatibility and hydrophobicity of electrospun PCL. The GH component of the hybrid scaffold provides a hydrophilic surface to improve the biological response of the cells, while the CE component increases the mechanical strength of the scaffold to provide enhanced mechanical support for the defect area and a stable environment for osteogenic differentiation. After analyzing characteristics of the hybrid scaffold such as hydrophilicity, pore difference, mechanical properties, and surface charge, we confirmed that the hybrid scaffold shows enhanced cell proliferation rate and apatite formation in simulated body fluid. Then, we evaluated drug release kinetics of CEGH and confirmed the sustained release of BMP-2. Finally, the enhanced osteogenic differentiation of CEGH with sustained release of BMP-2 was confirmed by Alizarin Red S staining and real-time PCR analysis.
骨再生是一个高度复杂的生理过程，受多种因素调控。特别是，骨模拟细胞外基质和可用的成骨生长因子，如骨形态发生蛋白（BMP），被认为是骨再生的关键因素。在这项研究中，我们开发了一种具有 BMP-2 持续释放功能的仿生混合支架（CEGH），以增强骨形成。该混合支架由负载 BMP-2 的冷冻纺丝聚己内酯（PCL）（CE）和多孔明胶/肝素冷冻凝胶（GH）组成，旨在克服冷冻凝胶相对较弱的机械性能、较差的生物相容性和静电纺丝 PCL 的疏水性等缺点。混合支架的 GH 部分提供了一个亲水表面，以改善细胞的生物反应，而 CE 部分增加了支架的机械强度，为缺损区域提供了增强的机械支撑和稳定的成骨分化环境。在分析了混合支架的特性，如亲水性、孔径差异、机械性能和表面电荷后，我们证实了混合支架在模拟体液中表现出更高的细胞增殖率和磷灰石形成。然后，我们评估了 CEGH 的药物释放动力学，并证实了 BMP-2 的持续释放。最后，通过茜素红 S 染色和实时 PCR 分析证实了 CEGH 具有持续释放 BMP-2 的增强成骨分化作用。
