CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
Biomacromolecules. 2023 Jul 10;24(7):3380-3396. doi: 10.1021/acs.biomac.3c00433. Epub 2023 Jun 19.
Dynamic G-quadruplex supramolecular hydrogels have aroused great interest in a broad range of bioapplications. However, neither the development of native extracellular matrix (ECM)-derived natural biopolymer-functionalized G-quadruplex hydrogels nor their use to create perfusable self-supporting hydrogels has been explored to date, despite their intrinsic potential as carrier vehicles of therapeutic agents, or even living cells in advanced regenerative therapies, or as platforms to enable the diffusion of nutrients and oxygen to sustain long-term cell survival. Herein, we developed a dynamic co-assembling multicomponent system that integrates guanosine (G), 3-aminophenylboronic acid functionalized hyaluronic acid (HA-PBA), and potassium chloride to bioengineer strong, homogeneous, and transparent HA-functionalized G-quadruplex hydrogels with injectable, thermo-reversible, conductive, and self-healing properties. The supramolecular polymeric hydrogels were developed by hydrogen bonding and stacking interactions between G coupled dynamic covalent boronate ester bonds to HA-PBA and stabilized by K ions, as demonstrated by a combination of experiments and molecular dynamics simulations. The intrinsic instability of the self-assembled G-quadruplex structures was used to bioengineer self-supporting perfusable multicomponent hydrogels with interconnected size and shape-tunable hollow microchannels when embedded in 3D methacrylated gelatin supporting matrices. The microchannel-embedded 3D constructs have shown enhanced cell viability when compared to the bulk hydrogels, holding great promise for being use as artificial vessels for enabling the diffusion of nutrients and oxygen essential for cell survival. The proposed approach opens new avenues on the use of ECM-derived natural biopolymer-functionalized dynamic G-quadruplex hydrogels to design next-generation smart systems for being used in tissue regeneration, drug screening, or organ-on-a-chip.
动态 G-四链体超分子水凝胶在广泛的生物应用中引起了极大的兴趣。然而，迄今为止，既没有开发天然细胞外基质（ECM）衍生的天然生物聚合物功能化 G-四链体水凝胶，也没有将其用于创建可灌注的自支撑水凝胶，尽管它们具有作为治疗剂载体，甚至是在高级再生治疗中作为活细胞，或作为允许营养物质和氧气扩散以维持长期细胞存活的平台的内在潜力。在这里，我们开发了一种动态共组装多组分系统，该系统集成了鸟嘌呤（G）、3-氨基苯硼酸功能化透明质酸（HA-PBA）和氯化钾，以生物工程制造具有可注射、热可逆、导电和自修复特性的强、均匀和透明的 HA 功能化 G-四链体水凝胶。超分子聚合物水凝胶通过 G 与 HA-PBA 之间的氢键和π堆积相互作用以及动态硼酸酯键形成，由 K 离子稳定，这一点通过实验和分子动力学模拟的结合得到了证明。自组装 G-四链体结构的固有不稳定性被用于生物工程制造自支撑可灌注的多组分水凝胶，当嵌入 3D 甲基丙烯酰化明胶支撑基质中时，这些水凝胶具有相互连接的尺寸和形状可调的中空微通道。与块状水凝胶相比，嵌入微通道的 3D 构建体显示出更高的细胞活力，为用作人工血管以允许营养物质和氧气扩散提供了巨大的潜力，这些物质对于细胞存活至关重要。所提出的方法为使用 ECM 衍生的天然生物聚合物功能化动态 G-四链体水凝胶设计用于组织再生、药物筛选或芯片上器官的下一代智能系统开辟了新途径。
