In Situ functionalization of Poly(hydroxyethyl methacrylate) Cryogels with Oligopeptides via β-Cyclodextrin–Adamantane Complexation for Studying Cell-Instructive Peptide Environment,ACS Applied Bio Materials

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In Situ functionalization of Poly(hydroxyethyl methacrylate) Cryogels with Oligopeptides via β-Cyclodextrin–Adamantane Complexation for Studying Cell-Instructive Peptide Environment
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-01-13 , DOI: 10.1021/acsabm.9b01059
Thai Duong Luong ₁ , Mohamed Zoughaib ₁ , Ruslan Garifullin _{1,

2} , Svetlana Kuznetsova ₁ , Mustafa O Guler ₃ , Timur I Abdullin ₁

Affiliation

Oligopeptides are versatile cell modulators resembling pleiotropic activities of ECM proteins and growth factors. Studying the role of cell-instructive peptide signals within 3D scaffolds, yet poorly known, requires effective approaches to introducing bioactive sequences into appropriate materials. We synthesized RGD and GHK motif based peptides 1 and 2 linked to the terminal adamantyl group (Ad) and their fluorescent derivatives 3 and 4. Poly(hydroxyethyl methacrylate) (pHEMA) cryogels with additional PEG/β-cyclodextrin (CD) units were prepared as an inert macroporous scaffold capable to bind the adamantylated peptides via affinity CD-Ad complexation. According to toluidine blue staining, the CD moieties were effectively and stably incorporated in the pHEMA cryogels at nanomolar amounts per milligram of material. The CD component gradually increased the thickness and swelling ability of the polymer walls of cryogels, resulting in a noticeable decrease in macropore size and modulation of viscoelastic properties. The labeled peptides exhibited fast kinetics of specific binding to the CD-modified cryogels and were simultaneously immobilized by coincubation. The peptide loading approached ca. 0.31 mg per cm² of cryogel sheet. A well-defined mitogenic effect of the immobilized peptides (2 < 1≪ 1 + 2) was revealed toward 3T3 and PC-12 cells. The synergistic action of RGD and GHK peptides induced a profound change in cell behavior/morphology attributed to a growth-factor-like activity of the composition. Altogether, our results provide an effective procedure for the preparation of CD-modified pHEMA cryogels and their uniform in situ functionalization with bioactive peptide(s) of interest and an informative study of cellular responses in the functionalized scaffolds.

中文翻译：

聚（甲基丙烯酸羟乙酯）冷冻凝胶与寡肽通过β-环糊精-金刚烷络合的原位功能化研究细胞指导性肽环境

寡肽是类似于 ECM 蛋白和生长因子的多效活性的多功能细胞调节剂。研究细胞指导肽信号在 3D 支架中的作用，但鲜为人知，需要有效的方法将生物活性序列引入适当的材料。我们合成了基于 RGD 和 GHK 基序的肽1和2 ，连接到末端金刚烷基 (Ad) 及其荧光衍生物3和4. 制备具有额外 PEG/β-环糊精 (CD) 单元的聚 (甲基丙烯酸羟乙酯) (pHEMA) 冷冻凝胶作为惰性大孔支架，能够通过亲和 CD-Ad 络合结合金刚烷基化肽。根据甲苯胺蓝染色，CD 部分以每毫克材料的纳摩尔量有效且稳定地掺入 pHEMA 冷冻凝胶中。CD 组分逐渐增加冷冻凝胶聚合物壁的厚度和溶胀能力，导致大孔径显着减小和粘弹性调节。标记的肽表现出与 CD 修饰的冷冻凝胶特异性结合的快速动力学，并同时通过共孵育进行固定。肽加载量接近约。0.31 毫克每平方厘米²冷冻凝胶片。固定化肽 ( 2 < 1 ≪ 1 + 2 ) 对 3T3 和 PC-12 细胞具有明确的促有丝分裂作用。RGD 和 GHK 肽的协同作用导致细胞行为/形态发生深刻变化，这归因于组合物的生长因子样活性。总而言之，我们的结果为制备 CD 修饰的 pHEMA 冷冻凝胶及其与感兴趣的生物活性肽的均匀原位功能化以及功能化支架中细胞反应的信息研究提供了有效的程序。

更新日期：2020-01-14

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