Panarello Andrew Philip, Seavey Corey Edward, Doshi Mona, Dickerson Andrew K, Kean Thomas J, Willenberg Bradley Jay
Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.
Department of Mechanical, Aerospace, and Biomedical Engineering, Tickle College of Engineering, University of Tennessee, Knoxville, TN 37996, USA.
Gels. 2022 Jun 14;8(6):376. doi: 10.3390/gels8060376.
Three-dimensional (3D) printing has great potential for creating tissues and organs to meet shortfalls in transplant supply, and biomaterial inks are key components of many such approaches. There is a need for biomaterial inks that facilitate integration, infiltration, and vascularization of targeted 3D-printed structures. This study is therefore focused on creating new biomaterial inks from self-assembled capillary alginate gel (Capgel), which possesses a unique microstructure of uniform tubular channels with tunable diameters and densities. First, extrusions of Capgel through needles (0.1-0.8 mm inner diameter) were investigated. It was found that Capgel ink extrudes as slurries of fractured and entangled particles, each retaining capillary microstructures, and that extruded line widths and particle sizes were both functions of needle inner diameter , specifically power-law relationships of ~ and ~, respectively. Next, various structures were successfully 3D-printed with Capgel ink, thus demonstrating that this biomaterial ink is stackable and self-supporting. To increase ink self-adherence, Capgel was coated with poly-L-lysine (PLL) to create a cationic "skin" prior to extrusion. It was hypothesized that, during extrusion of Capgel-PLL, the sheared particles fracture and thereby expose cryptic sites of negatively-charged biomaterial capable of forming new polyelectrolyte bonds with areas of the positively-charged PLL skin on neighboring entangled particles. This novel approach resulted in continuous, self-adherent extrusions that remained intact in solution. Human lung fibroblasts (HLFs) were then cultured on this ink to investigate biocompatibility. HLFs readily colonized Capgel-PLL ink and were strongly oriented by the capillary microstructures. This is the first description of successful 3D-printing with Capgel biomaterial ink as well as the first demonstration of the concept and formulation of a self-adherent Capgel-PLL biomaterial ink.
三维（3D）打印在制造组织和器官以满足移植供应短缺方面具有巨大潜力，生物材料墨水是许多此类方法的关键组成部分。需要能够促进目标3D打印结构的整合、渗透和血管化的生物材料墨水。因此，本研究专注于从自组装毛细管藻酸盐凝胶（Capgel）制备新型生物材料墨水，Capgel具有独特的微观结构，其均匀的管状通道直径和密度可调。首先，研究了Capgel通过针（内径0.1 - 0.8毫米）的挤出情况。发现Capgel墨水以破碎和缠结颗粒的浆料形式挤出，每个颗粒都保留了毛细管微观结构，并且挤出的线宽和颗粒尺寸都是针内径的函数，具体分别为和的幂律关系。接下来，使用Capgel墨水成功3D打印了各种结构，从而证明这种生物材料墨水是可堆叠且自支撑的。为了增加墨水的自粘性，在挤出之前，Capgel用聚-L-赖氨酸（PLL）进行了涂层处理，以形成阳离子“表皮”。据推测，在Capgel-PLL挤出过程中，剪切的颗粒会断裂，从而暴露出带负电荷的生物材料的隐蔽位点，这些位点能够与相邻缠结颗粒上带正电荷的PLL表皮区域形成新的聚电解质键。这种新方法产生了连续的、自粘性的挤出物，在溶液中保持完整。然后将人肺成纤维细胞（HLF）培养在这种墨水上以研究生物相容性。HLF很容易在Capgel-PLL墨水上定植，并被毛细管微观结构强烈定向。这是首次成功使用Capgel生物材料墨水进行3D打印的描述，也是首次展示自粘性Capgel-PLL生物材料墨水的概念和配方。
