Alarçin Emine, İzbudak Burçin, Yüce Erarslan Elif, Domingo Sherif, Tutar Rumeysa, Titi Kariman, Kocaaga Banu, Guner F Seniha, Bal-Öztürk Ayça
Department of Pharmaceutical Technology, Faculty of Pharmacy, Marmara University, Istanbul, Turkey.
Department of Stem Cell and Tissue Engineering, Institute of Health Sciences, Istinye University, Istanbul, Turkey.
J Biomed Mater Res A. 2023 Feb;111(2):209-223. doi: 10.1002/jbm.a.37450. Epub 2022 Oct 10.
Layered double hydroxides (LDHs) offer unique source of inspiration for design of bone mimetic biomaterials due to their superior mechanical properties, drug delivery capability and regulation cellular behaviors, particularly by divalent metal cations in their structure. Three-dimensional (3D) bioprinting of LDHs holds great promise as a novel strategy thanks to highly tunable physiochemical properties and shear-thinning ability of LDHs, which allow shape fidelity after deposition. Herein, we introduce a straightforward strategy for extrusion bioprinting of cell laden nanocomposite hydrogel bioink of gelatin methacryloyl (GelMA) biopolymer and LDHs nanoparticles. First, we synthesized LDHs by co-precipitation process and systematically examined the effect of LDHs addition on printing parameters such as printing pressure, extrusion rate, printing speed, and finally bioink printability in creating grid-like constructs. The developed hydrogel bioinks provided precise control over extrudability, extrusion uniformity, and structural integrity after deposition. Based on the printability and rheological analysis, the printability could be altered by controlling the concentration of LDHs, and printability was found to be ideal with the addition of 3 wt % LDHs. The addition of LDHs resulted in remarkably enhanced compressive strength from 652 kPa (G-LDH0) to 1168 kPa (G-LDH3). It was shown that the printed nanocomposite hydrogel scaffolds were able to support encapsulated osteoblast survival, spreading, and proliferation in the absence of any osteoinductive factors taking advantage of LDHs. In addition, cells encapsulated in G-LDH3 had a larger cell spreading area and higher cell aspect ratio than those encapsulated in G-LDH0. Altogether, the results demonstrated that the developed GelMA/LDHs nanocomposite hydrogel bioink revealed a high potential for extrusion bioprinting with high structural fidelity to fabricate implantable 3D hydrogel constructs for repair of bone defects.
层状双氢氧化物（LDHs）因其优异的机械性能、药物递送能力和调节细胞行为的能力，特别是其结构中的二价金属阳离子，为骨模拟生物材料的设计提供了独特的灵感来源。由于LDHs具有高度可调的物理化学性质和剪切变稀能力，能够在沉积后保持形状保真度，因此LDHs的三维（3D）生物打印作为一种新策略具有巨大潜力。在此，我们介绍一种直接的策略，用于挤出生物打印负载细胞的明胶甲基丙烯酰基（GelMA）生物聚合物和LDHs纳米颗粒的纳米复合水凝胶生物墨水。首先，我们通过共沉淀法合成了LDHs，并系统地研究了添加LDHs对打印参数的影响，如打印压力、挤出速率、打印速度，以及最终生物墨水在创建网格状结构时的可打印性。所开发的水凝胶生物墨水在沉积后能够精确控制挤出性、挤出均匀性和结构完整性。基于可打印性和流变学分析，可通过控制LDHs的浓度来改变可打印性，发现添加3 wt%的LDHs时可打印性理想。添加LDHs使抗压强度从652 kPa（G-LDH0）显著提高到1168 kPa（G-LDH3）。结果表明，利用LDHs，打印的纳米复合水凝胶支架能够在不存在任何骨诱导因子的情况下支持封装的成骨细胞存活、铺展和增殖。此外，封装在G-LDH3中的细胞比封装在G-LDH0中的细胞具有更大的细胞铺展面积和更高的细胞长宽比。总之，结果表明所开发的GelMA/LDHs纳米复合水凝胶生物墨水在挤出生物打印方面具有很高的潜力，能够以高结构保真度制造用于修复骨缺损的可植入3D水凝胶结构。
