Department of Biomedical Engineering, SKKU Institute for Convergence, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Republic of Korea.
Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Republic of Korea.
Tissue Eng Regen Med. 2022 Apr;19(2):281-287. doi: 10.1007/s13770-021-00388-3. Epub 2021 Sep 26.
Hyaluronic acid (HA) is a widely used polysaccharide in biomedical field because of its excellent biocompatibility. Its chemical structure can be modified with various functional groups. Recently, dopamine has been tethered onto the polymeric backbone to ensure long-term stability and tissue adhesiveness of HA hydrogel. However, the radical scavenging effect of dopamine on typical photo-induced crosslinking for hydrogels has not been specifically studied.
Photo-crosslinkable norbornene-modified HA (NorHA) was synthesized and crosslinked by dithiothreitol containing dopamine at different concentrations. During in situ ultraviolet light-triggered crosslinking, storage moduli were monitored using an oscillatory rheometer. Additionally, the amount of thiol utilized for HA crosslinking was investigated under the presence and absence of dopamine. Finally, doxorubicin was encapsulated in the hydrogels, and the drug loading efficiency and release kinetics were measured.
Adding dopamine into the NorHA pre-gel solution delayed the gelation time, yet the final storage modulus of the hydrogel remained constant. That is, dopamine might partially consume the energy required for thiol-ene reaction to generate semiquinone radicals. Furthermore, the residual thiols which were not involved in the crosslinking decreased when the hydrogel was formed at a high concentration of dopamine, indicating the formation of Michael adducts of semiquinone and thiols. Interestingly, the presence of dopamine in the hydrogel increased the loading efficiency of the hydrophobic drugs due to π-π stacking and hydrogen bonding between dopamine and drugs.
The presence of free catecholamines in a photo-crosslinkable polymer can delay the gelation time but improve the drug loading efficiency.
透明质酸（HA）由于其出色的生物相容性，在生物医学领域被广泛用作多糖。其化学结构可以用各种官能团进行修饰。最近，多巴胺被键合到聚合物主链上，以确保 HA 水凝胶的长期稳定性和组织粘附性。然而，多巴胺对水凝胶典型光交联的自由基清除作用尚未得到专门研究。
合成了含叠氮基团的可光交联透明质酸（NorHA），并在不同浓度的含多巴胺的二硫苏糖醇存在下交联。在原位紫外光引发交联过程中，使用振荡流变仪监测储能模量。此外，研究了多巴胺存在和不存在时用于 HA 交联的巯基的量。最后，将阿霉素包封在水凝胶中，并测量了药物的载药效率和释放动力学。
向 NorHA 预凝胶溶液中添加多巴胺会延迟凝胶时间，但水凝胶的最终储能模量保持不变。也就是说，多巴胺可能部分消耗了用于硫醇-烯反应生成半醌自由基所需的能量。此外，当多巴胺浓度较高时形成水凝胶，未参与交联的残留巯基减少，表明半醌和巯基形成迈克尔加成物。有趣的是，水凝胶中存在多巴胺会由于多巴胺和药物之间的π-π堆积和氢键作用而增加疏水性药物的载药效率。
光交联聚合物中游离儿茶酚胺的存在可以延迟凝胶时间，但可以提高药物载药效率。
