Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science & Technology, Seoul, 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul, 02792, Republic of Korea.
Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science & Technology, Seoul, 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul, 02792, Republic of Korea.
Biomaterials. 2019 Oct;218:119338. doi: 10.1016/j.biomaterials.2019.119338. Epub 2019 Jul 6.
Host-guest interaction using β-cyclodextrin (β-CD) and adamantane (Ad) allows facile modulation of guest molecule concentration in 3D hydrogels. Based on this phenomenon, we prepared a thermosensitive poly(organophosphazene) bearing β-CD hydrogel (β-CD PPZ, as host) and Ad-Arg-Gly-Asp (Ad-RGD, as guest). The structures of synthesized thermosensitive β-CD PPZ and Ad-RGD were confirmed by H NMR and FT-IR. The β-CD PPZ/Ad-RGD mixture was prepared by simple mixing and elicited thermosensitive properties with the formation of gelation in all Ad-RGDs mixing proportions at the body temperature. Strong and controlled host-guest interactions between β-CD PPZ and Ad-RGD were observed in 2D-NOESY, DLS, and TEM. Regulated MSC behaviors were elicited based on the use of controlled Ad-RGD amounts at the level of in vitro and in vivo. As the amount of Ad-RGD was increased in the β-CD PPZ hydrogel, MSC survival rate was enhanced and was prone to express osteogenic factors. While Ad-RGD is absent or low in hydrogel, relatively poor MSC survival rate and adipogenesis were exhibited. Altogether, we verified that survival rate and differentiation of MSCs could be controlled by host-guest interaction system with thermosensitive 3D hydrogel. This proposed 3D hydrogel controlling system with host-guest interaction is expected to be a platform technology as changing guest molecules.
主体-客体相互作用利用β-环糊精（β-CD）和金刚烷（Ad）可以轻松调节 3D 水凝胶中客体分子的浓度。基于这一现象，我们制备了一种负载β-CD 的温敏聚膦腈水凝胶（β-CD PPZ，作为主体）和金刚烷-精氨酸-甘氨酸-天冬氨酸（Ad-RGD，作为客体）。通过 1H NMR 和 FT-IR 确认了合成的温敏β-CD PPZ 和 Ad-RGD 的结构。通过简单混合制备了β-CD PPZ/Ad-RGD 混合物，并在所有 Ad-RGD 混合比例下在体温下形成凝胶化，表现出温敏特性。在 2D-NOESY、DLS 和 TEM 中观察到β-CD PPZ 和 Ad-RGD 之间的强而受控的主体-客体相互作用。基于在体外和体内使用受控的 Ad-RGD 量，调节了 MSC 的行为。随着β-CD PPZ 水凝胶中 Ad-RGD 数量的增加，MSC 的存活率得到提高，并且易于表达成骨因子。而在水凝胶中缺乏或低含量的 Ad-RGD 时，MSC 的存活率相对较差，表现出脂肪生成。总之，我们验证了 MSC 的存活率和分化可以通过具有温敏 3D 水凝胶的主体-客体相互作用系统来控制。这种具有主体-客体相互作用的 3D 水凝胶控制体系有望成为一种平台技术，可通过改变客体分子来实现。
