由于其热响应和光交联性能,基于明胶甲基丙烯酰基(GelMA)的生物材料已被广泛用作3D生物打印和各种生物医学应用的新型且有前途的生物墨水。然而,时间和温度依赖性流动行为的GelMA在溶胶-凝胶过渡态提出了巨大的挑战,当打印厚支架,也维持高细胞活力。此外,GelMA水凝胶的可转性和原位光交联能力使其成为局部药物递送应用的有希望的候选物。先前的研究已经报道了在用于治疗应用的GelMA支架中直接包封米诺环素(MH)。然而,由于其分子尺寸小,实现高浓度MH的延长和持续释放是具有挑战性的。这项研究的目的是探索GelMA生物墨水在挤出生物打印中的最佳挤出打印策略,考虑其时间和温度依赖性流动行为,然后研究其作为药物负载载体的应用,用于持续MH释放以在氧化应激下进行细胞保护。对GelMA的材料性能进行了表征,然后进行了考虑印刷适性和细胞生存性的印刷优化。金属离子介导的MH,硫酸葡聚糖(DS),采用镁形成纳米颗粒复合物(MH-DS)在GelMA中持续释放药物。此外,用GelMA打印体外模型,研究MH对氧化应激的细胞保护作用。我们的结果表明,印刷时间对GelMA的适印性和细胞存活率有显著影响,喷嘴温度,和GelMA浓度。基于可印刷性和细胞活力窗口确定最佳印刷区。使用来自最佳区域的参数打印的支架表现出优异的可印刷性和细胞活力。我们观察到,较低浓度的GelMA导致第一天MH从MH-DS的突释减少,导致与直接混合相比更持续的释放曲线。此外,在体外氧化应激模型中,释放的MH显着增加成纤维细胞的存活率。
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Owing to its thermoresponsive and photocrosslinking characteristics, gelatin methacryloyl (GelMA)-based biomaterials have gained widespread usage as a novel and promising
bioink for three-dimensional bioprinting and diverse biomedical applications. However, the flow behaviors of GelMA during the sol-gel transition, which are dependent on time and temperature, present significant challenges in printing thick scaffolds while maintaining high printability and cell viability. Moreover, the tunable properties and photocrosslinking capabilities of GelMA underscore its potential for localized drug delivery applications. Previous research has demonstrated the successful incorporation of minocycline (MH) into GelMA scaffolds for therapeutic applications. However, achieving a prolonged and sustained release of concentrated MH remains a challenge, primarily due to its small molecular size. The primary aim of this
study is to investigate an optimal extrusion printing method for GelMA
bioink in extrusion bioprinting, emphasizing its flow behaviors that are influenced by time and temperature. Additionally, this research seeks to explore the potential of GelMA
bioink as a carrier for the sustained release of MH, specifically targeting cellular protection against oxidative stress. The material properties of GelMA were assessed and further optimization of the printing process was conducted considering both printability and cell survival. To achieve sustained drug release within GelMA, the
study employed a mechanism using metal ion mediation to facilitate the interaction between MH, dextran sulfate (DS), and magnesium, leading to the formation of nanoparticle complexes (MH-DS). Furthermore, a GelMA-basedin vitromodel was developed in order to investigate the cellular protective properties of MH against oxidative stress. The experimental results revealed that the printability and cell viability of GelMA are significantly influenced by the printing duration, nozzle temperature, and GelMA concentrations. Optimal printing conditions were identified based on a thorough assessment of both printability and cell viability. Scaffolds printed under these optimal conditions exhibited exceptional printability and sustained high cell viability. Notably, it was found that lower GelMA concentrations reduced the initial burst release of MH from the MH-dextran sulfate (MH-DS) complexes, thus favoring more controlled, sustained release profiles. Additionally, MH released under these conditions significantly enhanced fibroblast viability in anin vitromodel simulating oxidative stress.