Department of Biologic and Material Sciences, Department of Biomedical Engineering, University of Michigan, 1011 N. University Ave, Room 2213, Ann Arbor, MI, 48109-1078, USA.
Adv Healthc Mater. 2019 May;8(9):e1801356. doi: 10.1002/adhm.201801356. Epub 2019 Mar 5.
Biomimetically designed materials matching the chemical and mechanical properties of tissue support higher mesenchymal stem cell (MSC) adhesion. However, directing cell-specific attachment and ensuring uniform cell distribution within the interior of 3D biomaterials remain key challenges in healing critical sized defects. Previously, a phage display derived MSC-specific peptide (DPIYALSWSGMA, DPI) was combined with a mineral binding sequence (VTKHLNQISQSY, VTK) to increase the magnitude and specificity of MSC attachment to calcium-phosphate biomaterials in 2D. This study investigates how DPI-VTK influences quantity and uniformity of iPS-MSC mediated bone and vasculature formation in vivo. There is greater bone formation in vivo when iPS-MSCs are transplanted on bone-like mineral (BLM) constructs coated with DPI-VTK compared to VTK (p < 0.002), uncoated BLM (p < 0.037), acellular BLM/DPI-VTK (p < 0.003), and acellular BLM controls (p < 0.01). This study demonstrates, for the first time, the ability of non-native phage-display designed peptides to spatially control uniform cell distribution on 3D scaffolds and increase the magnitude and uniformity of bone and vasculature formation in vivo. Taken together, the study validates phage display as a novel technology platform to engineer non-native peptides with the ability to drive cell specific attachment on biomaterials, direct bone regeneration, and engineer uniform vasculature in vivo.
仿生设计的材料与组织的化学和机械性能相匹配，支持更高的间充质干细胞（MSC）黏附。然而，在 3D 生物材料的内部引导细胞特异性附着并确保均匀的细胞分布仍然是修复临界尺寸缺陷的关键挑战。先前，一种噬菌体展示衍生的 MSC 特异性肽（DPIYALSWSGMA，DPI）与一个矿物结合序列（VTKHLNQISQSY，VTK）结合，以增加 MSC 对钙磷生物材料在 2D 中的附着的幅度和特异性。本研究调查了 DPI-VTK 如何影响 iPS-MSC 在体内介导的骨和血管形成的数量和均匀性。当 iPS-MSCs 移植到涂有 DPI-VTK 的类骨矿物质（BLM）构建体上时，体内的骨形成量大于涂有 VTK（p < 0.002）、未涂覆的 BLM（p < 0.037）、无细胞 BLM/DPI-VTK（p < 0.003）和无细胞 BLM 对照（p < 0.01）。本研究首次证明了非天然噬菌体展示设计的肽能够在 3D 支架上空间控制均匀的细胞分布，并增加体内骨和血管形成的幅度和均匀性。总之，该研究验证了噬菌体展示作为一种新型的技术平台，可以工程化具有在生物材料上驱动细胞特异性附着、引导骨再生和工程化体内均匀血管生成能力的非天然肽。
