Yabuuchi Kohei, Suzuki Mika, Liang Chen, Hashimoto Yoshihide, Kimura Tsuyoshi, Akiyoshi Kazunari, Kishida Akio
New Product Development Office, R&D Group, Healthcare Materials Division, Life Innovation SBU, Asahi Kasei Co., Chiyoda-ku, Tokyo 100-0006, Japan.
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
Gels. 2023 Oct 31;9(11):866. doi: 10.3390/gels9110866.
Nanogels are candidate biomaterials for tissue engineering and drug delivery. In the present study, a cholesterol-hyaluronic acid hydrogel was developed, and the pro-inflammatory response of macrophages to the hydrogel was investigated to determine its use in biomedical applications. Hyaluronic acid modified with cholesterol (modification rate: 0-15%) and maleimide (Chol-HA) was synthesized. The Chol-HA nanogel was formed through self-assembly via hydrophobic cholesterol interactions in aqueous solution. The Chol-HA hydrogel was formed through chemical crosslinking of the Chol-HA nanogel via a Michael addition reaction between the maleimide and thiol groups of 4arm-PEGSH. We found that the Chol-HA hydrogels with 5, 10, and 15% cholesterol inhibited the pro-inflammatory response of HiBiT-THP-1 cells, suggesting that the cholesterol contributed to the macrophage response. Furthermore, Interleukin 4 (IL-4) encapsulated in the hydrogel of the Chol-HA nanogel enhanced the inhibition of the inflammatory response in HiBiT-THP-1 cells. These results provide useful insights into the biomedical applications of hydrogels.
纳米凝胶是用于组织工程和药物递送的候选生物材料。在本研究中，开发了一种胆固醇 - 透明质酸水凝胶，并研究了巨噬细胞对该水凝胶的促炎反应，以确定其在生物医学应用中的用途。合成了用胆固醇（修饰率：0 - 15%）和马来酰亚胺修饰的透明质酸（Chol - HA）。Chol - HA纳米凝胶通过水溶液中疏水胆固醇相互作用的自组装形成。Chol - HA水凝胶通过4臂 - PEGSH的马来酰亚胺基团和硫醇基团之间的迈克尔加成反应对Chol - HA纳米凝胶进行化学交联而形成。我们发现含5%、10%和15%胆固醇的Chol - HA水凝胶抑制了HiBiT - THP - 1细胞的促炎反应，表明胆固醇对巨噬细胞反应有影响。此外，包裹在Chol - HA纳米凝胶水凝胶中的白细胞介素4（IL - 4）增强了对HiBiT - THP - 1细胞炎症反应的抑制。这些结果为水凝胶的生物医学应用提供了有用的见解。
