Diels–Alder “Clickable” Biodegradable Nanofibers: Benign Tailoring of Scaffolds for Biomolecular Immobilization and Cell Growth,Bioconjugate Chemistry

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Diels–Alder “Clickable” Biodegradable Nanofibers: Benign Tailoring of Scaffolds for Biomolecular Immobilization and Cell Growth
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2017-09-05 00:00:00 , DOI: 10.1021/acs.bioconjchem.7b00411
Ozlem Ipek Kalaoglu-Altan ₁ , Azize Kirac-Aydin ₁ , Burcu Sumer Bolu ₁ , Rana Sanyal ₁ , Amitav Sanyal ₁

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Biodegradable polymeric nanofibers have emerged as promising candidates for several biomedical applications such as tissue engineering and regenerative medicine. Many of these applications require modification of these nanofibers with small ligands or biomolecules such as peptides and other growth factors, which necessitates functionalization of these materials in mild and benign fashion. This study reports the design, synthesis, and functionalization of such nanofibers and evaluates their application as a cell culture scaffold. Polylactide based copolymers containing furan groups and triethylene glycol (TEG) units as side chains were synthesized using organocatalyzed ring opening polymerization. The furan moiety, an electron rich diene, provides “clickable” handles required for modification of nanofibers since they undergo facile cycloaddition reactions with maleimide-containing small molecules and ligands. The TEG units provide these fibers with hydrophilicity, enhanced biodegradability, and antibiofouling characteristics to minimize nonspecific adsorption. A series of copolymers with varying amounts of TEG units in their side chains were evaluated for fiber formation and antibiofouling characteristics to reveal that an incorporation of 7.5 mol % TEG-based monomer was optimal for nanofibers containing 20 mol % furan units. Facile functionalization of these nanofibers in a selective manner was demonstrated through attachment of a dienophile containing fluorophore, namely, fluorescein maleimide. To show efficient ligand-mediated bioconjugation, nanofibers were functionalized with a maleimide appended biotin, which enabled efficient attachment of the protein, Streptavidin. Importantly, the crucial role played by the TEG-based side chains was evident due to lack of any nonspecific attachment of protein to these nanofibers in the absence of biotin ligand. Furthermore, these nanofibers were conjugated with a cell adhesive cyclic peptide, cRGDfK-maleimide, at room temperature without the need of any additional catalyst. Importantly, comparison of the cell attachment onto nanofibers with and without the peptide demonstrated that fibers appended with the peptides promoted cells to spread nicely and protrude actin filaments for enhanced attachment to the support, whereas the cells on nonfunctionalized nanofibers showed a rounded up morphology with limited cellular spreading.

中文翻译：

Diels–Alder“可点击”的可生物降解纳米纤维：生物分子固定化和细胞生长的支架的良性剪裁。

可生物降解的聚合物纳米纤维已成为多种生物医学应用（如组织工程和再生医学）的有前途的候选者。这些应用中的许多要求使用小的配体或生物分子（如肽和其他生长因子）对这些纳米纤维进行修饰，这需要以温和而良性的方式对这些材料进行功能化。这项研究报告了这种纳米纤维的设计，合成和功能化，并评估了它们作为细胞培养支架的应用。使用有机催化的开环聚合反应合成了含有呋喃基和三甘醇（TEG）单元作为侧链的基于聚丙交酯的共聚物。呋喃部分，一种富电子的二烯，提供了纳米纤维改性所需的“可点击”的手柄，因为它们会与含马来酰亚胺的小分子和配体进行便捷的环加成反应。TEG单元可为这些纤维提供亲水性，增强的生物降解性和抗生物结垢特性，以最大程度地减少非特异性吸附。评价了在其侧链中具有不同量TEG单元的一系列共聚物的纤维形成和抗生物结垢特性，发现掺入7.5 mol％TEG基单体对于含有20 mol％呋喃单元的纳米纤维是最佳的。通过含有荧光团的亲二烯体，即荧光素马来酰亚胺的附着，证明了这些纳米纤维以选择性方式的容易的功能化。为了显示有效的配体介导的生物缀合，纳米纤维被附加了马来酰亚胺的生物素功能化，从而使蛋白质链霉亲和素能够有效附着。重要的是，由于在没有生物素配体的情况下蛋白质与这些纳米纤维之间没有任何非特异性结合，因此基于TEG的侧链发挥了至关重要的作用。此外，这些纳米纤维在室温下与细胞粘附环肽cRGDfK-马来酰亚胺偶联，而无需任何其他催化剂。重要的是，在有和没有肽的情况下，细胞附着在纳米纤维上的比较表明，附着有肽的纤维会促进细胞很好地扩散并突出肌动蛋白丝，以增强与支持物的附着，而在未官能化的纳米纤维上的细胞则表现出四舍五入的形态。细胞扩散。

更新日期：2017-09-05

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