Department of Mechanical Engineering and Mechanics, Drexel University, Philadelphia, PA 19104, United States of America.
School of Biomedical Engineering and Health Science Systems, Drexel University, Philadelphia, PA 19104, United States of America.
Biofabrication. 2024 Mar 28;16(2). doi: 10.1088/1758-5090/ad30c3.
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-basedmodel 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 anmodel simulating oxidative stress.
由于其温敏和光交联特性，明胶甲基丙烯酰（GelMA）基生物材料已广泛用作新型有前途的三维生物打印生物墨水，用于各种生物医学应用。然而，GelMA 在溶胶-凝胶转变过程中的流动行为取决于时间和温度，这在打印厚支架时带来了巨大的挑战，因为需要保持高的打印性和细胞活力。此外，GelMA 的可调特性和光交联能力突出了其在局部药物输送应用中的潜力。先前的研究已经证明，米诺环素（MH）成功地掺入 GelMA 支架中用于治疗应用。然而，实现 MH 的长时间和持续释放仍然是一个挑战，主要是由于其小分子尺寸。本研究的主要目的是研究 GelMA 生物墨水在挤出生物打印中的最佳挤出打印方法，强调其受时间和温度影响的流动行为。此外，本研究还旨在探索 GelMA 生物墨水作为 MH 持续释放载体的潜力，特别是针对细胞对抗氧化应激的保护。评估了 GelMA 的材料特性，并进一步优化了打印工艺，同时考虑了打印性和细胞存活率。为了在 GelMA 内实现药物的持续释放，研究采用了一种机制，利用金属离子介导促进 MH、葡聚糖硫酸盐（DS）和镁之间的相互作用，形成纳米颗粒复合物（MH-DS）。此外，还开发了一种基于 GelMA 的模型，以研究 MH 对氧化应激的细胞保护特性。实验结果表明，GelMA 的打印性和细胞活力受到打印持续时间、喷嘴温度和 GelMA 浓度的显著影响。基于对打印性和细胞活力的全面评估，确定了最佳打印条件。在这些最佳条件下打印的支架表现出出色的打印性和持续的高细胞活力。值得注意的是，发现较低的 GelMA 浓度降低了 MH 从 MH-葡聚糖硫酸盐（MH-DS）复合物中的初始突释，从而有利于更可控、持续的释放曲线。此外，在模拟氧化应激的模型中，这些条件下释放的 MH 显著提高了成纤维细胞的活力。
