Camci-Unal Gulden, Aubin Hug, Ahari Amirhossein Farajzadeh, Bae Hojae, Nichol Jason William, Khademhosseini Ali
Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA.
Soft Matter. 2010 Oct 21;6(20):5120-5126. doi: 10.1039/c0sm00508h.
A major challenge to the effective treatment of injured cardiovascular tissues is the promotion of endothelialization of damaged tissues and implanted devices. For this reason, there is a need for new biomaterials that promote endothelialization to enhance vascular repair. The goal of this work was to develop antibody-modified polysaccharide-based hydrogels that could selectively capture endothelial progenitor cells (EPCs). We showed that CD34 antibody immobilization on hyaluronic acid (HA) hydrogels provides a suitable surface to capture EPCs. The effect of CD34 antibody immobilization on EPC adhesion was found to be dependent on antibody concentration. The highest level of EPC attachment was found to be 52.2 cells per mm(2) on 1% HA gels modified with 25 μg mL(-1) antibody concentration. Macrophages did not exhibit significant attachment on these modified hydrogel surfaces compared to the EPCs, demonstrating the selectivity of the system. Hydrogels containing only HA, with or without immobilized CD34, did not allow for spreading of EPCs 48 h after cell seeding, even though the cells were adhered to the hydrogel surface. To promote spreading of EPCs, 2% (w/v) gelatin methacrylate (GelMA) containing HA hydrogels were synthesized and shown to improve cell spreading and elongation. This strategy could potentially be useful to enhance the biocompatibility of implants such as artificial heart valves or in other tissue engineering applications where formation of vascular structures is required.
有效治疗受损心血管组织面临的一个主要挑战是促进受损组织和植入装置的内皮化。因此，需要新型生物材料来促进内皮化以增强血管修复。这项工作的目标是开发能够选择性捕获内皮祖细胞（EPCs）的抗体修饰的多糖基水凝胶。我们发现，将CD34抗体固定在透明质酸（HA）水凝胶上可提供一个捕获EPCs的合适表面。发现CD34抗体固定对EPCs黏附的影响取决于抗体浓度。在抗体浓度为25μg/mL修饰的1%HA凝胶上，EPCs附着的最高水平为每平方毫米52.2个细胞。与EPCs相比，巨噬细胞在这些修饰的水凝胶表面上没有显著附着，这证明了该系统的选择性。即使细胞黏附在水凝胶表面，仅含HA的水凝胶（无论有无固定化CD34）在细胞接种48小时后都不允许EPCs铺展。为了促进EPCs铺展，合成了含HA的2%（w/v）甲基丙烯酸明胶（GelMA）水凝胶，并证明其可改善细胞铺展和伸长。这种策略可能有助于提高人工心脏瓣膜等植入物的生物相容性，或在其他需要形成血管结构的组织工程应用中发挥作用。
