Data from: Engineering the microstructure and spatial bioactivity of MAP scaffolds instructs vasculogenesis in vitro and translates to vessel formation in vivo

This data was collected at Duke University in the Segura Lab. The goal of these studies was to explore the impact of microgel heterogeneity (microstructure, spatial bioactivity) on vasculogensis both in vitro and in vivo.
In tissues where the vasculature is either lacking or abnormal, biomaterials can be designed to promote vessel formation and enhance tissue repair. In this work, we independently tune the microstructure and bioactivity of microporous annealed particle (MAP) scaffolds to guide cell growth in 3D and promote de novo assembly of endothelial progenitor-like cells into vessels. We implement both in silico characterization and in vitro experimentation to elucidate an optimal scaffold formulation for vasculogenesis. We determine that MAP scaffolds with pore volumes on the same order of magnitude as cells facilitate cell growth and vacuole formation. We achieve spatial control over cell spreading by incorporating adhesive microgels in well-mixed, heterogeneous MAP scaffolds. While we demonstrate that integrin engagement is the primary driver of network formation in these materials, introducing adhesive microgels loaded with heparin nanoparticles leads to the formation of vascular tubes after 3 days in culture. We then show in vivo that this unique scaffold formulation enhances vessel maturation in a wound healing model and instructs differential vascular development in the tumor microenvironment. Taken together, this work determines the optimal microstructure and ligand presentation within MAP scaffolds that leads to vascular constructs in vitro and facilitates vessel formation in vivo.
The details of the motivation, methods, analysis, and results can be found in our publication (DOI 10.1002/adfm.202400567)

本数据集采集自杜克大学塞古拉实验室（Segura Lab）。本研究的核心目标为探究微凝胶异质性（microgel heterogeneity，即微观结构、空间生物活性）对体内外（in vitro/in vivo）血管生成（vasculogenesis）的影响。
在血管缺失或异常的组织中，可通过设计生物材料促进血管生成并改善组织修复效果。本研究通过独立调控微孔退火颗粒（microporous annealed particle, MAP）支架的微观结构与生物活性，实现三维环境下的细胞生长引导，并促进内皮祖细胞样细胞（endothelial progenitor-like cells）从头组装（de novo assembly）为血管结构。本研究结合计算机模拟表征（in silico characterization）与体外实验，阐明适用于血管生成的最优支架配方。研究发现，孔隙体积与细胞尺寸处于同一数量级的MAP支架可有效促进细胞生长与空泡形成（vacuole formation）。通过将粘附性微凝胶（adhesive microgels）引入混合均匀的异质性MAP支架，本研究实现了细胞铺展的空间精准调控。尽管本研究证实整合素结合（integrin engagement）是此类材料中血管网络形成的核心驱动因素，但引入负载肝素纳米颗粒（heparin nanoparticles）的粘附性微凝胶后，培养3天即可观察到血管管状结构（vascular tubes）的形成。后续体内实验表明，该独特的支架配方可在伤口愈合模型（wound healing model）中促进血管成熟，并在肿瘤微环境（tumor microenvironment）中诱导差异化的血管发育。综上，本研究明确了MAP支架内的最优微观结构与配体呈递（ligand presentation）策略，可在体外构建血管结构，并在体内促进血管生成。
本研究的研究动机、实验方法、数据分析与结果细节可参阅已发表论文（DOI: 10.1002/adfm.202400567）