Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH, United States of America.
Biofabrication. 2020 Jul 21;12(4):045006. doi: 10.1088/1758-5090/ab97a1.
We develop and characterize a biomaterial formulation and robotic methods tailored for intracorporeal tissue engineering (TE) via direct-write (DW) 3D printing. Intracorporeal TE is defined as the biofabrication of 3D TE scaffolds inside of a living patient, in a minimally invasive manner. A biomaterial for intracorporeal TE requires to be 3D printable and crosslinkable via mechanisms that are safe to native tissues and feasible at physiological temperature (37 °C). The cell-laden biomaterial (bioink) preparation and bioprinting methods must support cell viability. Additionally, the biomaterial and bioprinting method must enable the spatially accurate intracorporeal 3D delivery of the biomaterial, and the biomaterial must adhere to or integrate into the native tissue. Current biomaterial formulations do not meet all the presumed intracorporeal DW TE requirements. We demonstrate that a specific formulation of gelatin methacryloyl (GelMA)/Laponite/methylcellulose (GLM) biomaterial system can be 3D printed at physiological temperature and crosslinked using visible light to construct 3D TE scaffolds with clinically relevant dimensions and consistent structures. Cell viability of 71%-77% and consistent mechanical properties over 21 d are reported. Rheological modifiers, Laponite and methylcellulose, extend the degradation time of the scaffolds. The DW modality enables the piercing of the soft tissue and over-extrusion of the biomaterial into the tissue, creating a novel interlocking mechanism with soft, hydrated native tissue mimics and animal muscle with a 3.5-4 fold increase in the biomaterial/tissue adhesion strength compared to printing on top of the tissue. The developed GLM biomaterial and robotic interlocking mechanism pave the way towards intracorporeal TE.
我们开发并表征了一种生物材料配方和机器人方法，这些方法专门用于通过直接写入（DW）3D 打印进行腔内组织工程（TE）。腔内 TE 被定义为在活体内患者体内以微创方式生物制造 3D TE 支架。用于腔内 TE 的生物材料需要能够通过对天然组织安全且在生理温度（37°C）下可行的机制进行 3D 打印和交联。载细胞的生物材料（生物墨水）的制备和生物打印方法必须支持细胞活力。此外，生物材料和生物打印方法必须能够实现生物材料在体内的空间精确 3D 输送，并且生物材料必须附着在或整合到天然组织上。目前的生物材料配方并不能满足所有假定的腔内 DW TE 要求。我们证明了明胶甲基丙烯酰（GelMA）/Laponite/甲基纤维素（GLM）生物材料系统的特定配方可以在生理温度下进行 3D 打印，并使用可见光交联，以构建具有临床相关尺寸和一致结构的 3D TE 支架。报告了 71％-77％的细胞活力和 21 天内一致的机械性能。流变改性剂 Laponite 和甲基纤维素延长了支架的降解时间。DW 方式能够刺穿软组织并将生物材料过度挤出到组织中，与在组织顶部打印相比，与柔软、水合的天然组织模拟物和动物肌肉形成新颖的互锁机制，使生物材料/组织的粘附强度增加 3.5-4 倍。开发的 GLM 生物材料和机器人互锁机制为腔内 TE 铺平了道路。
