3D打印行业is currently seeking feedback on resin 3D printing. Send your insights now and take theSpotlight on Resin 3D Printing Survey.
Researchers atHarvard Medical Schooland四川大学have developed a novel means of 3D bioprinting live human muscle-tendon tissues.
As opposed to normal extrusion bioprinting, which involves depositing cells along X and Y axes, the team’s ‘cryo-bioprinting’ process sees them frozen and stacked vertically, in a way that allows for the creation of freestanding, mixed-cell tissues.
According to the scientists, their technique also yields tissues that are more robust and versatile than those produced via conventional bioprinting, particularly when it comes to those anisotropic in nature, thus they say it could now find regenerative medicine, drug discovery, or personalized therapeutic applications.
An extrusion bioprinting alternative?
Few 3D bioprinting technologies have so far made it to market, and the field remains at a relatively early stage of development in this respect. However, of those used at an experimental level, the scientists say that many still rely on extrusion-based approaches, which are often functional, but when it comes to printing tissues that rely heavily on alignment, like muscle and nerve fibers, they tend to come up short.
To overcome these tissue-stacking issues, the researchers have therefore turned to ‘ice-templating,’ a freezing process that causes microchannels to form within cell-laden hydrogel-based structures once they thaw. Naturally, doing so would ordinarily damage the viability of such cells, so to prevent this, the team loaded theirs with the cryoprotective agents (CPAs) melezitose and dimethyl sulfoxide.
一旦冻结，研究人员随后使用紫外线（UV）光垂直交叉这种新型的Bio-Ink，并将其挤入由高分辨率的蜂窝样微通道网络组成的组织中，能够支持各种不同类型的细胞，无论它们是骨骼肌肌细胞或人脐静脉内皮细胞。
“Our results indicate that [our] bio-ink, consisting of gelatin methacryloyl and CPAs, could be effectively used in vertical 3D cryo-bioprinting to enable cell encapsulation at high viability,” explained the team in their paper. “With the help of the interconnected, anisotropic, gradient microchannels formed by directional freezing during the process, the desired cellular alignments were also realized.”
‘Cryo-bioprinting’ a human tendon
在证明了方法的生存力之后，科学家继续评估其在创建更复杂的多个细胞类型组织结构中的功效。为了实现这一目标，该团队最初使用带有同轴喷嘴的3D BioProinter将细胞沉积到垂直的核心壳结构中，这一过程使他们能够精确控制材料沉积，同时最多使用八个不同的油墨。
至关重要的是，在这些组织中，研究人员还发现，他们的方法使他们能够创建可定制的各向异性微通道，从而促进细胞生长，尽管成功水平有所不同。经过几次试验印刷后，将梅糖糖和DMSO分别为8％和10％的生物企业被证明是最有效的，产生的组织，从60-80％的细胞生存能力波动。
However, despite these mixed results, which the scientists attributed to potential variations in their experimental processes, they went on to take their approach a step further, by applying it in the creation of a tendon ‘junction,’ a tissue mass that in its organic form, transmits the force of a muscle’s contraction through the tendon to the human skeletal system.
During this process, cryo-bioprinting was said to prove ideal, as it enabled the creation of a junction in which its lower cells were highly aligned, with its fibroblasts less so, mimicking the structure of its natural counterpart. Once printed, the resulting tendon was cultured for seven days, in which its muscular and vascular bio-inks demonstrably interfaced, growing into a dense microvascular network.
结果，即使团队承认他们的方法目前具有打印高度的限制，可以阻止其在某些体内应用中使用，但他们坚持认为，它仍可以在创建肌肉骨骼模型中部署，从而有可能帮助发展患者 -具体的治疗并提高我们对人体的理解。
“It is rationally anticipated that our vertical 3D cryo-bioprinting strategy may find broad usage in engineering a variety of tissues that feature-oriented internal cellular and extracellular matrix arrangements,” concluded the team in their paper. “Another possible utility of the method lies in the creation of in vitro musculoskeletal models for biological studies, drug discovery and personalized medicine.”
新颖的生物打印方法
鉴于3D Bioprinting是一项新兴技术，因此其格式不断发生变化并不令人惊讶，研究人员不断将创新的新想法带入了现场。就在上个月，英国的科学家University of BirminghamandUniversity of Huddersfield，揭示他们已经开发了novel skin 3D bioprinting technique这样可以治疗慢性伤口。
在其他地方，在更商业层面，Inventia Life Scienceraised $25 million towards the development of itsRASTRUM 3D bioprinting technologyin December 2021. In effect, the firm’s approach is designed to enable the layering of cell-loaded droplets onto one another at pace, in a way that allows them to join on contact and doesn’t affect their overall viability.
Looking even further back, researchers at伦敦帝国学院还尝试了细胞冻结作为一种手段bioprinting viable human implants. In a paper, now published four years ago, a team there sought to combine 3D printing and cryogenics as a means of replicating the texture of soft tissues in the body, and fooling the brain and lungs into accepting grafts as if they were organic.
The researchers’ findings are detailed in their paper titled “Vertical Extrusion Cryo(bio)printing for Anisotropic Tissue Manufacturing.”
The study was co-authored by Zeyu Luo, Guosheng Tang, Hossein Ravanbakhsh, Wanlu Li, Mian Wang, Xiao Kuang, Carlos Ezio Garcia mendez-Mijares, Liming Lian, Sili Yi, Junlong Liao, Maobin Xie, Jie Guo, Zongke Zhou andYu Shrike Zhang。
要了解最新的3D印刷新闻，请不要忘记订阅3D打印行业newsletter或跟随我们推特或喜欢我们的页面Facebook.
For a deeper dive into additive manufacturing, you can now subscribe to ourYouTube频道，包括讨论，汇报和3D打印进程的镜头。
Are you looking for a job in the additive manufacturing industry? Visit3D Printing Jobsfor a selection of roles in the industry.
Featured image shows a diagram of the team’s 3D bioprinted muscle-tendon structure. Image via Harvard Medical School/Sichuan University.
