Department of Chemistry, Faculty of Science, National University of Singapore, S05-03-09, 3Science Drive 3, Singapore 117576, Singapore.
Biomaterials. 2010 Oct;31(29):7455-67. doi: 10.1016/j.biomaterials.2010.06.020.
Tissue constructs that mimic the in vivo cell-cell and cell-matrix interactions are especially useful for applications involving the cell- dense and matrix- poor internal organs. Rapid and precise arrangement of cells into functional tissue constructs remains a challenge in tissue engineering. We demonstrate rapid assembly of C3A cells into multi- cell structures using a dendrimeric intercellular linker. The linker is composed of oleyl- polyethylene glycol (PEG) derivatives conjugated to a 16 arms- polypropylenimine hexadecaamine (DAB) dendrimer. The positively charged multivalent dendrimer concentrates the linker onto the negatively charged cell surface to facilitate efficient insertion of the hydrophobic oleyl groups into the cellular membrane. Bringing linker- treated cells into close proximity to each other via mechanical means such as centrifugation and micromanipulation enables their rapid assembly into multi- cellular structures within minutes. The cells exhibit high levels of viability, proliferation, three- dimensional (3D) cell morphology and other functions in the constructs. We constructed defined multi- cellular structures such as rings, sheets or branching rods that can serve as potential tissue building blocks to be further assembled into complex 3D tissue constructs for biomedical applications.
组织构建体模拟体内细胞-细胞和细胞-基质相互作用，特别适用于涉及细胞密集和基质稀少的内部器官的应用。快速而精确地将细胞排列成功能性组织构建体仍然是组织工程中的一个挑战。我们使用树枝状细胞间连接子展示了 C3A 细胞的快速组装成多细胞结构。该连接子由连接到 16 臂聚丙稀亚胺十六胺（DAB）树枝状大分子的油酰聚乙二醇（PEG）衍生物组成。带正电荷的多价树枝状大分子将连接子浓缩到带负电荷的细胞膜上，以促进疏水性油酰基插入细胞膜。通过机械手段（如离心和微操作）使带连接子的细胞彼此接近，可在几分钟内快速组装成多细胞结构。细胞在构建体中表现出高存活率、增殖、三维（3D）细胞形态和其他功能。我们构建了定义明确的多细胞结构，如环、薄片或分支棒，它们可用作潜在的组织构建块，进一步组装成用于生物医学应用的复杂 3D 组织构建体。
