Direct-write 3D printing and characterization of a GelMA-based biomaterial for intracorporeal tissue
Direct-write 3D printing and characterization of a GelMA-based biomaterial for intracorporeal tissue
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DOI：
10.1088/1758-5090/ab97a1
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发表时间：
2020-10-01
期刊：
影响因子：
9
通讯作者：
Hoelzle, D. J.
中科院分区：
文献类型：
--
作者：
Adib, A. Asghari;Sheikhi, A.;Hoelzle, D. J.
我们开发和表征了一种生物材料配方和机器人方法，通过直写（DW）3D打印为脑内组织工程（TE）量身定制。颅内TE被定义为以微创方式在活体患者体内植入3D TE支架的生物制品。用于颅内移植的生物材料需要通过对天然组织安全且在生理温度（37摄氏度）下可行的机制进行3D打印和交联。载有细胞的生物材料（生物墨水）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的空间精确的颅内3D递送，并且生物材料必须粘附或整合到天然组织中。目前的生物材料配方不符合所有假定的颅内DW TE要求。我们证明了明胶甲基丙烯酰（GelMA）/Laponite（R）/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。报道了71%-77%的细胞活力和超过21天的一致的机械性能。流变改性剂Laponite（R）和甲基纤维素延长了支架的降解时间。DW模态能够刺穿软组织并将生物材料过度挤出到组织中，从而与柔软的水合天然组织模拟物和动物肌肉形成新型互锁机制，与在组织顶部印刷相比，生物材料/组织粘附强度增加3.5-4倍。开发的GLM生物材料和机器人互锁机制为Intracereblete铺平了道路。
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 degrees 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(R)/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(R)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.