Thermoresponsive Brush Coatings for Cell Sheet Engineering with Low Protein Adsorption above the Polymers' Phase Transition Temperature.

IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-11-18 Epub Date: 2024-11-05 DOI:10.1021/acsabm.4c01127
Alexander Schweigerdt, Daniel D Stöbener, Johanna Scholz, Andreas Schäfer, Marie Weinhart
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引用次数: 0

Abstract

Thermoresponsive polymer coatings on cell culture substrates enable noninvasive cell detachment and cell sheet fabrication for biomedical applications. Optimized coatings should support controlled culture and detachment of various cell types and allow chemical modifications, e.g., to introduce specific growth factors for enhanced gene expression. Furthermore, the sterilization and storage stability of the coatings must be assessed for translational attempts. Poly(glycidyl ether) (PGE) brush coatings with short alkoxy side chains provide a versatile platform for cell culture and detachment, but their polyether backbones are susceptible to oxidation and degradation. Thus, we rationally designed potential alternatives with thermoresponsive glycerol-based block copolymers comprising a stable polyacrylate or polymethacrylate backbone and an oligomeric benzophenone (BP)-based anchor. The resulting poly(ethoxy hydroxypropyl acrylate-b-benzophenone acrylate) (pEHPA-b-BP) and poly(ethoxy hydroxypropyl methacrylate-b-benzophenone methacrylate) (pEHPMA-b-BP) block copolymers preserve the short alkoxy-terminated side chains of the PGE derived structure on a stable, but hydrophobic, aliphatic backbone. The amphiphilicity balance is maintained through incorporated hydroxyl groups, which simultaneously can be used for chemical modification. The polymers were tailored into brush coatings on polystyrene surfaces via directed adsorption using the BP oligomer anchor. The resulting coatings with thickness values up to ∼3 nm supported efficient adhesion and proliferation of human fibroblasts despite minimal protein adsorption. The conditions for cell sheet fabrication on pEHPA-b-BP were gentler and more reliable than on pEHPMA-b-BP, which required additional cooling. Hence, the stability of pEHPA-b-BP and PGE coatings was evaluated post gamma and formaldehyde (FO) gas sterilization. Gamma sterilization partially degraded PGE coatings and hindered cell detachment on pEHPA-b-BP. In contrast, FO sterilization only slowed detachment on PGE coatings and had no adverse effects on pEHPA-b-BP, maintaining their efficient performance in cell sheet fabrication.

用于细胞片工程的热致伸缩刷涂层,在聚合物相变温度以上具有较低的蛋白质吸附性。
细胞培养基质上的热致伸缩性聚合物涂层可实现非侵入式细胞分离和细胞薄片制造,用于生物医学应用。经过优化的涂层应支持各种类型细胞的可控培养和分离,并允许进行化学修饰,例如引入特定生长因子以增强基因表达。此外,还必须评估涂层的灭菌和储存稳定性,以便进行转化尝试。具有短烷氧基侧链的聚缩水甘油醚(PGE)刷涂层为细胞培养和分离提供了一个多功能平台,但其聚醚骨架容易氧化和降解。因此,我们合理地设计了具有热致伸缩性的甘油基嵌段共聚物作为潜在的替代品,这种嵌段共聚物由稳定的聚丙烯酸酯或聚甲基丙烯酸酯骨架和低聚二苯甲酮(BP)基锚组成。由此产生的聚(乙氧基羟丙基丙烯酸酯-二苯甲酮丙烯酸酯)(pEHPA-b-BP)和聚(乙氧基羟丙基甲基丙烯酸酯-二苯甲酮甲基丙烯酸酯)(pEHPMA-b-BP)嵌段共聚物在稳定但疏水的脂肪族骨架上保留了 PGE 衍生结构的短烷氧基端侧链。两亲性平衡是通过加入羟基来维持的,羟基同时可用于化学修饰。通过使用 BP 低聚物锚进行定向吸附,聚合物被定制为聚苯乙烯表面的刷状涂层。尽管蛋白质吸附量极少,但所产生的涂层厚度可达 3 纳米,可支持人类成纤维细胞的有效粘附和增殖。与需要额外冷却的 pEHPMA-b-BP 相比,在 pEHPA-b-BP 上制造细胞片的条件更温和、更可靠。因此,对 pEHPA-b-BP 和 PGE 涂层在伽马射线和甲醛(FO)气体灭菌后的稳定性进行了评估。伽马射线灭菌部分降解了 PGE 涂层,阻碍了 pEHPA-b-BP 上的细胞脱落。相比之下,FO 灭菌只减缓了 PGE 涂层的脱落速度,对 pEHPA-b-BP 没有不利影响,从而保持了它们在细胞片制造中的高效性能。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
期刊介绍: ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.
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