Department of Biotechnology, Yonsei University , Seoul 120-749, Republic of Korea.
Biomacromolecules. 2013 Jun 10;14(6):2004-13. doi: 10.1021/bm400352d. Epub 2013 May 15.
Alginate hydrogels are for various biomedical applications including tissue engineering, cell therapy, and drug delivery. However, it is not easy to control swelling or viscoelastic and biophysical properties of alginate hydrogels prepared by conventional cross-linking methods (ionic interaction using divalent cations). In this study, we describe a bioinspired approach for preparing divalent ion-free alginate hydrogels that exhibit tunable physical and mechanical properties and improved biocompatibility due to the absence of cations in the gel matrices. We conjugated dopamine, a minimalized adhesive motif found in the holdfast pads of mussels, to alginate backbones (alginate-catechol) and the tethered catechols underwent oxidative cross-linking. This resulted in divalent cation-free alginate hydrogels. The swelling ratios and moduli of the alginate-catechol hydrogels are readily tunable, which is difficult to achieve in ionic bond-based alginate hydrogels. Furthermore, alginate-catechol hydrogels enhanced the survival of various human primary cells including stem cells in the three-dimensional gel matrix, indicating that intrinsic cytotoxicity caused by divalent cations becomes negligible when employing catechol oxidation for alginate cross-linking. The inflammatory response in vivo was also significantly attenuated compared to conventional alginate hydrogels with calcium cross-linking. This biomimetic approach for the preparation of alginate hydrogels may provide a novel platform technology to develop tunable, functional, biocompatible, three-dimensional scaffolds for tissue engineering and cell therapy.
海藻酸盐水凝胶在各种生物医学应用中都有使用，包括组织工程、细胞治疗和药物输送。然而，通过传统的交联方法（使用二价阳离子的离子相互作用）制备的海藻酸盐水凝胶，其溶胀或粘弹性和生物物理性质不易控制。在本研究中，我们描述了一种仿生方法，用于制备无二价离子的海藻酸盐水凝胶，由于凝胶基质中没有阳离子，因此具有可调节的物理和机械性能以及提高的生物相容性。我们将最小化的黏附基序多巴胺（贻贝固着垫中的一种）与海藻酸盐主链偶联（海藻酸盐-儿茶酚），并使连接的儿茶酚发生氧化交联。这导致形成无二价离子的海藻酸盐水凝胶。海藻酸盐-儿茶酚水凝胶的溶胀率和模量很容易调节，这在基于离子键的海藻酸盐水凝胶中很难实现。此外，海藻酸盐-儿茶酚水凝胶增强了各种人类原代细胞（包括干细胞）在三维凝胶基质中的存活，这表明当使用儿茶酚氧化交联海藻酸盐时，二价阳离子引起的固有细胞毒性变得可以忽略不计。与具有钙离子交联的传统海藻酸盐水凝胶相比，体内的炎症反应也明显减弱。这种仿生方法制备海藻酸盐水凝胶可能为组织工程和细胞治疗提供一种新型的可调、功能、生物相容的三维支架平台技术。
