Department of Materials Science and Engineering, Drexel University, Philadelphia, PA 19104, USA.
Department of Materials Science and Engineering, Drexel University, Philadelphia, PA 19104, USA; School of Biomedical Engineering, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325011, China; Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Sciences, Wenzhou, Zhejiang 325000, China.
Biomaterials. 2019 Mar;197:244-254. doi: 10.1016/j.biomaterials.2019.01.020. Epub 2019 Jan 11.
Biological materials are superior to synthetic biomaterials in biocompatibility and active interactions with cells. Here, a new class of biological materials, cell membrane-derived hydrogel scaffolds are reported for harnessing these advantages. To form macroporous scaffolds, vesicles derived from red blood cell membranes (RBCMs) are chemically crosslinked via cryogelation. The RBCM scaffolds with a pore size of around 70 μm are soft and injectable. Highly biocompatible scaffolds are typically made of superhydrophilic polymers and lack the ability to encapsulate and release hydrophobic drugs in a controlled manner. However, hydrophobic molecules can be efficiently encapsulated inside RBCM scaffolds and be sustainedly released. RBCM scaffolds show low neutrophil infiltration after subcutaneous injection in mice, and a significantly higher number of infiltrated macrophages than methacrylate alginate (MA-alginate) scaffolds. According to gene expression and surface markers, these macrophages have an M2-like phenotype, which is anti-inflammatory and immune suppressive. There are also higher percentages of macrophages presenting immunosuppressive PD-L1 in RBCM-scaffolds than in MA-alginate scaffolds. Interestingly, the concentrations of anti-inflammatory cytokine, IL-10 in both types of scaffolds are higher than those in normal organ tissues. This study sheds light on cell membrane-derived hydrogels, which can actively modulate cells in unique ways unavailable to existing hydrogel scaffolds.
生物材料在生物相容性和与细胞的积极相互作用方面优于合成生物材料。在这里，我们报道了一类新型的生物材料，即细胞膜衍生的水凝胶支架，用于利用这些优势。为了形成大孔支架，通过冷冻凝胶化将源自红细胞膜 (RBCM) 的囊泡化学交联。孔径约为 70 μm 的 RBCM 支架柔软且可注射。高度生物相容的支架通常由超亲水聚合物制成，缺乏以可控方式封装和释放疏水性药物的能力。然而，疏水分子可以有效地封装在 RBCM 支架内，并持续释放。RBCM 支架在小鼠皮下注射后，中性粒细胞浸润程度较低，浸润的巨噬细胞数量明显高于甲基丙烯酰化藻酸盐 (MA-alginate) 支架。根据基因表达和表面标志物，这些巨噬细胞具有 M2 样表型，具有抗炎和免疫抑制作用。与 MA-alginate 支架相比，RBCM 支架中呈现免疫抑制 PD-L1 的巨噬细胞比例也更高。有趣的是，两种支架中抗炎细胞因子 IL-10 的浓度均高于正常器官组织中的浓度。这项研究揭示了细胞膜衍生的水凝胶，它可以以现有水凝胶支架无法实现的独特方式主动调节细胞。
