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交联策略对基于透明质酸和 ε-聚赖氨酸水凝胶的生物学、抗菌和物理化学性能的影响。

Effect of crosslinking strategy on the biological, antibacterial and physicochemical performance of hyaluronic acid and ɛ-polylysine based hydrogels.

机构信息

Rudolfs Cimdins Riga Biomaterials Innovations and Development Centre of RTU, Institute of General Chemical Engineering, Faculty of Materials Science and Applied Chemistry, Riga Technical University, Pulka St. 3/3, Riga LV-1007, Latvia; Baltic Biomaterials Centre of Excellence, Headquarters at Riga Technical University, Riga, Latvia.

AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland.

出版信息

Int J Biol Macromol. 2022 May 31;208:995-1008. doi: 10.1016/j.ijbiomac.2022.03.207. Epub 2022 Apr 1.

DOI:10.1016/j.ijbiomac.2022.03.207
PMID:35378161
Abstract

The design of multifunctional hydrogels based on bioactive hyaluronic acid (HA) and antibacterial cationic polymer ɛ-poly-l-lysine (ε-PL) is a promising tool in tissue engineering applications. In the current study, we have designed hyaluronic acid and ɛ-polylysine composite hydrogel systems with antibacterial and cell attractive properties. Two distinct crosslinking approaches were used: the physical crosslinking based on electrostatic attractions and the chemical crosslinking of charged functional groups (-NH and -COOH). The impact of the crosslinking strategy on fabricated hydrogel molecular structure, swelling behavior, gel fraction, morphology, porosity, viscoelastic properties, antibacterial activity, and in vitro biocompatibility was evaluated. Both chemically and physically crosslinked HA/ԑ-PL hydrogels demonstrated fast swelling behavior and long-term stability for at least 28 days, as well as similar order of stiffness (10-30 kPa). We demonstrated that physically crosslinked hydrogels inhibited over 99.999% of Gram-negative E. coli, while chemically crosslinking strategy led to the antibacterial efficiency decrease. However, cell viability was significantly improved, confirming the importance of the applied crosslinking approach to the antibacterial activity and in vitro biocompatibility. The distinct differences in the physicochemical and biological properties of the developed materials provide new opportunities to design next-generation functional composite hydrogel systems.

摘要

基于生物活性透明质酸(HA)和抗菌阳离子聚合物 ε-聚-L-赖氨酸(ε-PL)的多功能水凝胶的设计是组织工程应用中的一种很有前途的工具。在目前的研究中,我们设计了具有抗菌和细胞吸引力的透明质酸和 ε-聚赖氨酸复合水凝胶系统。使用了两种不同的交联方法:基于静电吸引力的物理交联和带电荷官能团(-NH 和 -COOH)的化学交联。交联策略对制备的水凝胶分子结构、溶胀行为、凝胶分数、形态、孔隙率、粘弹性、抗菌活性和体外生物相容性的影响进行了评估。化学交联和物理交联的 HA/ԑ-PL 水凝胶均表现出快速溶胀行为和至少 28 天的长期稳定性,以及相似的硬度顺序(10-30kPa)。我们证明了物理交联水凝胶抑制了超过 99.999%的革兰氏阴性大肠杆菌,而化学交联策略导致抗菌效率降低。然而,细胞活力显著提高,这证实了所应用的交联方法对抗菌活性和体外生物相容性的重要性。所开发材料的物理化学和生物学性质的明显差异为设计下一代功能性复合水凝胶系统提供了新的机会。

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