Institute for Complex Molecular Systems , Eindhoven University of Technology , P.O. Box 513 , 5600 MB Eindhoven , The Netherlands.
Biomacromolecules. 2018 Jul 9;19(7):2610-2617. doi: 10.1021/acs.biomac.8b00219. Epub 2018 May 2.
High concentrations of supplemented growth factors can cause oversaturation and adverse effects in in vitro and in vivo studies, though these supraphysiological concentrations are often required due to the low stability of growth factors. Here we demonstrate the stabilization of TGF-β1 and BMP4 using supramolecular polymers. Inspired by heparan sulfate, sulfonated peptides were presented on a supramolecular polymer to allow for noncovalent binding to growth factors in solution. After mixing with excipient molecules, both TGF-β1 and BMP4 were shown to have a prolonged half-life compared to the growth factors free in solution. Moreover, high cellular response was measured by a luciferase assay, indicating that TGF-β1 remained highly active upon binding to the supramolecular assembly. The results demonstrate that significant lower concentrations of growth factors can be used when supramolecular polymers bearing growth factor binding moieties are implemented. This approach can also be exploited in hydrogel systems to control growth factor release.
高浓度的补充生长因子会在体外和体内研究中导致过饱和和不良反应，尽管由于生长因子的低稳定性，通常需要这些超生理浓度。在这里，我们使用超分子聚合物来稳定 TGF-β1 和 BMP4。受肝素硫酸盐的启发，在超分子聚合物上呈现磺化肽，以允许在溶液中非共价结合生长因子。与赋形剂分子混合后，与游离在溶液中的生长因子相比，TGF-β1 和 BMP4 的半衰期都明显延长。此外，通过荧光素酶测定法测量了高细胞反应，表明 TGF-β1 在与超分子组装结合后仍保持高度活性。结果表明，当使用带有生长因子结合部分的超分子聚合物时，可以使用显著更低浓度的生长因子。这种方法也可以在水凝胶系统中用于控制生长因子的释放。
