Zhao Chenjia, Ji Jingyuan, Yin Tianjun, Yang Jing, Pang Yuan, Sun Wei
Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China.
Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing 100084, China.
Biomedicines. 2021 Sep 23;9(10):1298. doi: 10.3390/biomedicines9101298.
Hydrogels have recently received attention as delivery carriers owing to their good biocompatibility and structural similarity to natural extracellular matrices. However, the utilization of traditional single-network (SN) hydrogels is limited by poor mechanical properties and burst drug release. Therefore, we developed a novel double-network (DN) hydrogel, which employs an alginate (ALG)/polyethylene glycol diacrylate (PEGDA) network to adjust the mechanical strength and a positively charged monomer AETAC (2-(acryloyloxy)ethyl]trimethyl-ammonium chloride) to regulate the release curve of the electronegative anti-human papillomavirus (HPV) protein (bovine β-lactoglobulin modified with 3-hydroxyphthalic anhydride) based on an affinity-controlled delivery mechanism. The results show that the double-network hydrogel strongly inhibits the burst release, and the burst release amount is about one-third of that of the single-network hydrogel. By changing the concentration of the photoinitiator, the mechanical strength of the DN hydrogels can be adjusted to meet the stiffness requirements for various tissues within the range of 0.71 kPa to 10.30 kPa. Compared with the SN hydrogels, the DN hydrogels exhibit almost twice the mechanical strength and have smaller micropores. Cytotoxicity tests indicated that these SN and DN hydrogels were not cytotoxic with the result of over 100% relative proliferation rate of the HUVECs. Furthermore, DN hydrogels can significantly alleviate the burst release of antiviral proteins and prolong the release time to more than 14 days. Finally, we utilized digital light processing (DLP) technology to verify the printability of the DN hydrogel. Our study indicates that ALG/PEGDA-AETAC DN hydrogels could serve as platforms for delivering proteins and show promise for diverse tissue engineering applications.
由于水凝胶具有良好的生物相容性以及与天然细胞外基质相似的结构，近年来它们作为药物递送载体受到了关注。然而，传统单网络（SN）水凝胶的应用受到其较差的机械性能和药物突释的限制。因此，我们开发了一种新型双网络（DN）水凝胶，它采用藻酸盐（ALG）/聚乙二醇二丙烯酸酯（PEGDA）网络来调节机械强度，并使用带正电荷的单体AETAC（2-(丙烯酰氧基)乙基]三甲基氯化铵）基于亲和控制的递送机制来调节带负电荷的抗人乳头瘤病毒（HPV）蛋白（用3-羟基邻苯二甲酸酐修饰的牛β-乳球蛋白）的释放曲线。结果表明，双网络水凝胶强烈抑制突释，突释量约为单网络水凝胶的三分之一。通过改变光引发剂的浓度，DN水凝胶的机械强度可在0.71 kPa至10.30 kPa范围内进行调节，以满足不同组织的硬度要求。与SN水凝胶相比，DN水凝胶的机械强度几乎提高了一倍，且微孔更小。细胞毒性测试表明，这些SN和DN水凝胶无细胞毒性，人脐静脉内皮细胞（HUVECs）的相对增殖率超过100%。此外，DN水凝胶可显著减轻抗病毒蛋白的突释，并将释放时间延长至14天以上。最后，我们利用数字光处理（DLP）技术验证了DN水凝胶的可打印性。我们的研究表明，ALG/PEGDA-AETAC DN水凝胶可作为蛋白质递送平台，并在多种组织工程应用中显示出前景。
