In this work, a novel enzymatically crosslinked injectable hydrogel comprising hyaluronic acid (HyA), dopamine (DA), and 3-(4-hydroxyphenyl) propionic acid (HPA) conjugates was successfully developed. To the best of our knowledge, it is the first time that HPA is conjugated to a HyA-based backbone. In situ hydrogelation of HyA-DA-HPA occurred in the presence of hydrogen peroxide (H₂O₂) as an oxidant and horseradish peroxidase (HRP) as a catalyst. Proton nuclear magnetic resonance and Fourier transform infrared spectroscopy were used to characterize the chemical reactions between HyA, DA, and HPA. Gel formation completed between 3 s to 5 min depending on the concentrations of polymer, HRP, and H₂O₂. Crosslinked HyA-DA-HPA gels acquired storage moduli ranging from ∼100 Pa to ∼20 000 Pa (at f = 2000 rad s⁻¹). Biocompatibility of the hydrogels was examined with human mesenchymal stem cells (hMSCs) and human induced pluripotent stem cell-derived neural stem cells. The hydrogels made of 2.0 w/v% HyA-DA-HPA hydrogels, 0.24 U ml⁻¹ HRP and ≤ 0.5 mol ml⁻¹ H₂O₂ were found biocompatible with hMSCs cultured on and encapsulated within the hydrogels. Since HyA serves as a backbone of the extracellular matrix in the central nervous system (CNS) and DA acquires the ability to restore dopaminergic neurons, use of this injectable HyA-DA-HPA hydrogel for stem cell transplantation is a potential treatment strategy for CNS repair and regeneration.

在这项工作中，成功开发了一种新型酶交联可注射水凝胶，包括透明质酸 (HyA)、多巴胺 (DA) 和 3-(4-羟基苯基) 丙酸 (HPA) 偶联物​​。据我们所知，这是 HPA 第一次与基于 HyA 的主干结合。HyA-DA-HPA 的原位水凝胶化发生在过氧化氢 (H ₂ O ₂ ) 作为氧化剂和辣根过氧化物酶 (HRP) 作为催化剂的存在下。质子核磁共振和傅里叶变换红外光谱用于表征 HyA、DA 和 HPA 之间的化学反应。凝胶形成在 3 秒到 5 分钟之间完成，具体取决于聚合物、HRP 和 H ₂ O _2的浓度. 交联的 HyA-DA-HPA 凝胶获得的储能模量范围为 ∼100 Pa 至 ∼20 000 Pa（在 f = 2000 rad s ^-1时）。用人间充质干细胞 (hMSCs) 和人诱导的多能干细胞衍生的神经干细胞检查水凝胶的生物相容性。由 2.0 w/v% HyA-DA-HPA 水凝胶、0.24 U ml ^-1 HRP 和 ≤ 0.5制成的水凝胶发现mol ml ^-1 H ₂ O ₂与在水凝胶上培养并封装在水凝胶内的hMSC具有生物相容性。由于 HyA 是中枢神经系统 (CNS) 中细胞外基质的骨架，并且 DA 具有恢复多巴胺能神经元的能力，因此使用这种可注射的 HyA-DA-HPA 水凝胶进行干细胞移植是 CNS 修复的潜在治疗策略和再生。