Center for Advanced Biomaterials for Health Care, Interdisciplinary Research Centre on Biomaterials, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci, 80125 Napoli, Italy.
Acta Biomater. 2012 Sep;8(9):3294-301. doi: 10.1016/j.actbio.2012.05.019. Epub 2012 May 27.
Angiogenesis occurs through a cascade of events controlled by complex multiple signals that are orchestrated according to specific spatial patterns and temporal sequences. Vascularization is a central issue in most tissue engineering applications. However, only a better insight into spatio-temporal signal presentation can help in controlling and guiding angiogenesis in vivo. To this end, versatile and accessible material platforms are required in order to study angiogenic events in a systematic way. In this work we report a three-dimensional porous polyethylene glycol (PEG) diacrylate hydrogel bioactivated with heparin that is able to deliver vascular endothelial growth factor (VEGF) in a sustained and controlled manner. The efficiency of the material has been tested both in vitro and in vivo. In particular, the VEGF released from the hydrogel induces cell proliferation when tested on HUVECs, retains its bioactivity up to 21days, as demonstrated by Matrigel assay, and, when implanted on a chorion allantoic membrane, the hydrogel shows superior angiogenic potential in stimulating new vessel formation compared with unfunctionalized hydrogels. Moreover, in the light of potential tissue regeneration studies, the proposed hydrogel has been modified with adhesion peptides (RGD) to enable cell colonization. The porous hydrogel reported here can be used as a valid tool to characterize angiogenesis, and, possibly, other biological processes, in different experimental set-ups.
血管生成是通过一系列受复杂多重信号控制的级联事件发生的，这些信号根据特定的空间模式和时间序列进行协调。血管生成是大多数组织工程应用中的一个核心问题。然而，只有更好地了解时空信号呈现方式，才能有助于控制和引导体内血管生成。为此，需要多功能且易于获取的材料平台，以便系统地研究血管生成事件。在这项工作中，我们报告了一种用肝素生物激活的三维多孔聚乙二醇（PEG）二丙烯酸酯水凝胶，能够以持续和可控的方式输送血管内皮生长因子（VEGF）。该材料的效率已经在体外和体内进行了测试。特别是，当在 HUVEC 上测试时，水凝胶中释放的 VEGF 会诱导细胞增殖，如 Matrigel 测定所示，其生物活性可保持 21 天，当植入绒毛尿囊膜时，与未功能化的水凝胶相比，水凝胶在刺激新血管形成方面具有更好的血管生成潜力。此外，鉴于潜在的组织再生研究，已经用粘附肽（RGD）对所提出的水凝胶进行了修饰，以实现细胞定植。这里报道的多孔水凝胶可用作不同实验设置中血管生成的有效工具，并可能用于其他生物过程。
