Abstract:
Biomedical applications such as drug delivery, tissue engineering, and functional surface coating rely on switchable adsorption and desorption of specialized guest molecules. Poly(dehydroalanine), a polyzwitterion containing pH-dependent positive and negative charges, shows promise for such reversible loading, especially when integrated into a gel network. Herein, we present the fabrication of poly(dehydroalanine)-derived gels of different size scales and evaluate them with respect to their practical use in biomedicine. Already existing protocols for bulk gelation were remodeled to derive suitable reaction conditions for droplet-based microfluidic synthesis. Depending on the layout of the microfluidic chip, microgels with a size of approximately 30 μm or 200 μm were obtained, whose crosslinking density can be increased by implementing a multi-arm crosslinker. We analyzed the effects of the crosslinker species on composition, permeability, and softness and show that the microgels exhibit advantageous properties inherent to zwitterionic polymer systems, including high hydrophilicity as well as pH- and ionic strength-sensitivity. We demonstrate pH-regulated uptake and release of fluorescent model dyes before testing the adsorption of a small antimicrobial peptide, LL-37. Quantification of the peptide accommodated within the microgels reveals the impact of size and crosslinking density of the microgels. Biocompatibility of the microgels was validated by cell tests.
摘要:
生物医学应用,如药物输送,组织工程,和功能性表面涂层依赖于特殊客体分子的可转换吸附和解吸。聚(脱氢丙氨酸),含有pH依赖性正电荷和负电荷的多两性离子,显示出这种可逆加载的希望,特别是当整合到凝胶网络中时。在这里,我们介绍了不同尺寸的聚(脱氢丙氨酸)衍生凝胶的制造,并评估了它们在生物医学中的实际应用。对已经存在的用于本体凝胶化的方案进行改造,以得出用于基于液滴的微流体合成的合适的反应条件。根据微流控芯片的布局,获得尺寸约为30μm或200μm的微凝胶,其交联密度可以通过实施多臂交联剂来增加。我们分析了交联剂种类对组成的影响,渗透性,和柔软性,并表明微凝胶表现出两性离子聚合物体系固有的有利性质,包括高亲水性以及pH和离子强度敏感性。在测试小的抗菌肽的吸附之前,我们证明了pH调节的荧光模型染料的吸收和释放,LL-37.微凝胶内容纳的肽的定量揭示了微凝胶的大小和交联密度的影响。通过细胞测试验证了微凝胶的生物相容性。