关于将促炎和抗炎细胞因子束缚到水凝胶中对人间充质干细胞迁移、降解和形态学影响的流变学研究。
A Rheological Study on the Effect of Tethering Pro- and Anti-Inflammatory Cytokines into Hydrogels on Human Mesenchymal Stem Cell Migration, Degradation, and Morphology.
发表日期:2024 Jul 03
作者:
Thomas C O'Shea, Kiera J Croland, Ahmad Salem, Rylie Urbanski, Kelly M Schultz
来源:
BIOMACROMOLECULES
摘要:
聚合物肽水凝胶被设计为可植入材料,可输送人间充质干细胞(hMSC)来治疗伤口。大多数伤口无需干预即可自行愈合。在正常的愈合过程中,细胞因子从伤口释放,形成浓度梯度,导致细胞从天然生态位定向迁移到伤口部位。我们的工作从这个过程中获得灵感,并将细胞因子均匀地束缚到支架中,以测量细胞介导的降解和运动的变化。这是在材料中设计细胞因子浓度梯度以指导细胞迁移的第一步。我们测量了具有共价束缚细胞因子(肿瘤坏死因子-α (TNF-α) 或转化生长因子-β (TGF-β))的水凝胶支架中流变特性、封装细胞介导的细胞周降解和迁移的变化。 TNF-α 在伤口愈合的早期阶段表达,引起炎症反应。 TGF-β 在伤口愈合的后期释放,引起周围组织的抗炎反应。两种细胞因子都会引起定向细胞迁移。当将任一细胞因子束缚在没有封装 hMSC 的聚合物网络中时,我们测量到模量或临界松弛指数没有统计学上的显着差异。这表明添加束缚细胞因子后支架结构和流变学没有改变。结合多粒子追踪微流变学 (MPT) 和带有束缚细胞因子的水凝胶中的活细胞成像,测量 hMSC 运动性、形态和细胞介导的降解的增加。我们测量到,将 TNF-α 束缚到水凝胶中会增加封装后早期的细胞重塑,而将 TGF-β 束缚到支架中会增加后期的细胞重塑。我们测量了 TGF-β 或 TNF-α 的束缚增强了细胞拉伸以及随后的迁移。这项工作提供了流变学表征,可用于设计在细胞周区域呈现化学线索以指导细胞迁移的新材料。
Polymer-peptide hydrogels are being designed as implantable materials that deliver human mesenchymal stem cells (hMSCs) to treat wounds. Most wounds can progress through the healing process without intervention. During the normal healing process, cytokines are released from the wound to create a concentration gradient, which causes directed cell migration from the native niche to the wound site. Our work takes inspiration from this process and uniformly tethers cytokines into the scaffold to measure changes in cell-mediated degradation and motility. This is the first step in designing cytokine concentration gradients into the material to direct cell migration. We measure changes in rheological properties, encapsulated cell-mediated pericellular degradation and migration in a hydrogel scaffold with covalently tethered cytokines, either tumor necrosis factor-α (TNF-α) or transforming growth factor-β (TGF-β). TNF-α is expressed in early stages of wound healing causing an inflammatory response. TGF-β is released in later stages of wound healing causing an anti-inflammatory response in the surrounding tissue. Both cytokines cause directed cell migration. We measure no statistically significant difference in modulus or the critical relaxation exponent when tethering either cytokine in the polymeric network without encapsulated hMSCs. This indicates that the scaffold structure and rheology is unchanged by the addition of tethered cytokines. Increases in hMSC motility, morphology and cell-mediated degradation are measured using a combination of multiple particle tracking microrheology (MPT) and live-cell imaging in hydrogels with tethered cytokines. We measure that tethering TNF-α into the hydrogel increases cellular remodeling on earlier days postencapsulation and tethering TGF-β into the scaffold increases cellular remodeling on later days. We measure tethering either TGF-β or TNF-α enhances cell stretching and, subsequently, migration. This work provides rheological characterization that can be used to design new materials that present chemical cues in the pericellular region to direct cell migration.