Department of Biomedical Engineering, Purdue School of Engineering and Technology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, United States of America.
Biomed Mater. 2021 May 28;16(4). doi: 10.1088/1748-605X/ac01b0.
Hydrogels with tunable properties are highly desirable in tissue engineering applications as they can serve as artificial extracellular matrix to control cellular fate processes, including adhesion, migration, differentiation, and other phenotypic changes via matrix induced mechanotransduction. Poly(-glutamic acid) (PGA) is an natural anionic polypeptide that has excellent biocompatibility, biodegradability, and water solubility. Moreover, the abundant carboxylic acids on PGA can be readily modified to introduce additional functionality or facilitate chemical crosslinking. PGA and its derivatives have been widely used in tissue engineering applications. However, no prior work has explored orthogonal crosslinking of PGA hydrogels by thiol-norbornene (NB) chemistry. In this study, we report the synthesis and orthogonal crosslinking of PGA-norbornene (PGANB) hydrogels. PGANB was synthesized by standard carbodiimide chemistry and crosslinked into hydrogels via either photopolymerization or enzymatic reaction. Moduli of PGA hydrogels were readily tuned by controlling thiol-NB crosslinking conditions or stoichiometric ratio of functional groups. Orthogonally crosslinked PGA hydrogels were used to evaluate the influence of mechanical cues of hydrogel substrate on the phenotype of naïve human monocytes and M0 macrophages in 3D culture.
具有可调特性的水凝胶在组织工程应用中非常理想，因为它们可以作为人工细胞外基质，通过基质诱导的机械转导来控制细胞命运过程，包括黏附、迁移、分化和其他表型变化。聚（谷氨酸）（PGA）是一种天然阴离子多肽，具有极好的生物相容性、可生物降解性和水溶性。此外，PGA 上丰富的羧酸可以很容易地进行修饰，以引入额外的功能或促进化学交联。PGA 及其衍生物已广泛应用于组织工程应用。然而，以前没有人探索过通过硫醇-降冰片烯（NB）化学对 PGA 水凝胶进行正交交联。在这项研究中，我们报告了 PGA-降冰片烯（PGANB）水凝胶的合成和正交交联。PGANB 通过标准碳二亚胺化学合成，并通过光聚合或酶反应交联成水凝胶。通过控制硫醇-NB 交联条件或官能团的化学计量比，很容易调节 PGA 水凝胶的模量。正交交联的 PGA 水凝胶用于评估水凝胶基质的机械线索对 3D 培养中幼稚人单核细胞和 M0 巨噬细胞表型的影响。
