Department of Chemistry and Chemical Biology, McMaster University , 1280 Main Street West, Hamilton, Ontario L8S 4M1, Canada.
Department of Chemical and Biological Engineering and the BioFrontiers Institute, University of Colorado Boulder , Jennie Smoly Caruthers Biotechnology Building, 3415 Colorado Avenue, Boulder, Colorado 80303, United States.
Biomacromolecules. 2017 Dec 11;18(12):4054-4059. doi: 10.1021/acs.biomac.7b01115. Epub 2017 Oct 26.
A common issue with hydrogel formulations is batch-to-batch irreproducibility originating from poorly defined polymer precursors. Here, we report the use of dendritic polymer end-groups to address this issue and maintain reproducibility between batches of poly(ethylene glycol) (PEG) hydrogels. Specifically, we synthesized two end-functionalized PEG chains: one with azide-terminated first- and second-generation dendrons and the other with strained cyclooctynes. The two complementary azide and alkyne polymers react via strain-promoted alkyne-azide cycloaddition (SPAAC) to produce hydrogels quickly in the absence of additional reagents or catalyst at low polymer concentrations. Hydrogels made with first-generation dendrons gelled in minutes and exhibited a small degree of swelling when incubated in PBS buffer at 37 °C, whereas hydrogels made from second-generation dendrons gelled in seconds with almost no swelling upon incubation at 37 °C. In both cases, the hydrogels proved reproducible, resulting in identical Young's modulus values from different batches. The hydrogels prepared with second-generation dendrons were seeded with human mesenchymal stem cells and showed high cell viability as well as cell spreading over a two-week time frame. These studies show that the SPAAC hydrogels are noncytotoxic and are capable of supporting cell growth.
水凝胶制剂的一个常见问题是，由于聚合物前体定义不明确，导致批间重复性差。在这里，我们报告使用树枝状聚合物端基来解决这个问题，并保持聚乙二醇（PEG）水凝胶批次间的重现性。具体来说，我们合成了两种端基官能化的 PEG 链：一种带有叠氮端基的第一代和第二代树枝状大分子，另一种带有张力环辛炔。这两种互补的叠氮和炔聚合物通过应变促进的炔-叠氮环加成（SPAAC）反应，在没有额外试剂或催化剂的情况下，在低聚合物浓度下快速生成水凝胶。用第一代树枝状大分子制成的水凝胶在几分钟内凝胶化，并在 37°C 的 PBS 缓冲液中孵育时表现出较小的溶胀程度，而用第二代树枝状大分子制成的水凝胶在几秒钟内凝胶化，在 37°C 下孵育时几乎没有溶胀。在这两种情况下，水凝胶都具有重现性，导致不同批次的杨氏模量值相同。用第二代树枝状大分子制备的水凝胶接种了人骨髓间充质干细胞，显示出高细胞活力和细胞在两周时间内的扩展。这些研究表明，SPAAC 水凝胶无细胞毒性，并能够支持细胞生长。
