来自威特沃特斯兰大学have assessed the challenges of using hydrogel-based bio-inks for 3D printing tissues, and made recommendations to enhance the applications of the technology.
科学家发现，尽管它对3D印刷组织具有安全性和有效性，但生物打印基于该过程中使用的生物材料的成本，完整性和强度的局限性。根据研究团队的说法，只有新颖的生物INK的发展才能使多细胞和多材料生物打印的大规模生产和采用。
The increasing adoption of 3D bioprinting
3D生物打印通常被应用于解决供体短缺和器官短缺的发生率。3D打印过程降低了免疫原性，因为基于水凝胶的生物INK是患者特异性的，这会导致器官排斥的减少和根据需求增强的供应。更重要的是，用于创建此类组织的生物企业基于诸如藻酸盐等水凝胶框架，藻酸盐具有较低的毒性和成本，并显示出更高的生物相容性。
While bioprinting encompasses a variety of methods such as Selective Laser Sintering (SLS), extrusion, and inkjet bioprinting, each method has several advantages over conventional tissue seeding for tissue engineering. 3D bioprinting for instance, can be used to create biomimetic structures based on a 3D scan from a patient’s damaged or injured body organ, allowing for the production of a patient-specific structure.
同时，在传统方法中，细胞的放置涉及将它们植入化学生长激素的支架中，这是组织工程细胞生长和开发所必需的。随后是由于其热塑性和生物降解性，使用聚合物（PGA）等聚合物（PGA）进行体内植入。这种方法有许多缺点，包括冗长的时间表，无法产生血管结构以及所使用的PGA材料的局限性。
3D bioprinting overcomes many of these issues, by using a CAD model to develop a 3D organization of living cells within a temporary biodegradable scaffold. This allows for the simultaneous dispensing of biomaterials and cells, resulting in seeding efficiency and the prevention of non-homogenous cell distribution because of postfabrication seeding. The researchers aimed to assess the advantages and limitations of different 3D tissue engineering techniques, and recommend areas where they can be improved upon.
研究人员对3D生物打印的评估
Assessing the hydrogels that are commonly used to create cell-laden structures within the 3D bioprinting process, the researchers praised their flexibility. The soft materials can be engineered to mimic the extracellular tissue microenvironment, enabling their medical application as biosensors, scaffolds for tissue regeneration, and drug delivery technology. Nonetheless, the researchers also highlighted limitations to certain hydrogels that can induce various side effects stimulated by polymerization residues. The erosion and degradation of the polymer network over time, can result in cellular death, central nervous system damage, and skin or ocular irritation.
The researchers suggest that using a reversible-deactivation radical polymerization technique, which periodically attaches and detaches active molecules or residues, could prevent the undesirable outcomes produced during polymerization. Moreover, according to the research team, during the extraction procedure, cell temperature, oxygen, carbon dioxide, and pH levels are often ignored, and this is essential to their viability. Citing a lack of research into effects of cells on the rheological behavior of bio-inks, the research team added that increasing cell density often leads to a decrease in the crosslinking ability.
Another issue raised by the South African researchers was the need for a new bio-ink that maintains a low viscosity, while bearing a consistency that allows for the formation of a solid or semisolid structure postprinting. This intermediate thickness demonstrates significant challenges, and impedes upon the suitability and feasibility of the process for large-scale manufacturing. Printing in high-density perfluorocarbon (PFC) fluid, was found to be a superior method when compared to the commonly used method of printing from a medium of air. The hydrogel droplets printed submerged in PFC, exhibited an increased contact angle, decreased flatness, and reduced diameter as compared to printing in an air medium.
Cross-linking was also demonstrated to be effective, and the introduction of a 10% wt/vol of CaCl2 via aerosol dispensing, showed an enhancement in the viscosity of an alginate solution used as a hydrogel-based bio-ink. This resulted in a hydrogel alginate bio-ink that demonstrated significantly improved mechanical strength, and ability to support cellular activities. Nonetheless, photocrosslinking also includes the exposure of ultraviolet (UV) light radiation to biological entities, and this can generate cytotoxic free radicals and stimulate local inflammation.
The researchers concluded that the selection of material deployed in 3D bioprinting is vital to the successful creation of 3D printed tissues. Current biomaterials used in 3D printing are limited to alginate, cellulose, gelatin, polyacrylates, and hyaluronic acid, and the research team suggested that a novel bio-ink will ultimately need to be developed. This material will need to be capable of fabricating multifunctional structures with appropriate mechanical strength, in order to support cellular viability and printability. According to the South African researchers, its creation will require a multidisciplinary approach, that consists of practicing clinical surgeons and pharmacists, and is not just limited to research scientists.
使用3D打印来创建生物组织
近年来已经设计了一系列的生物材料，以便能够制造3D生物打印组织。
来自University of Colorado Denverand theSouthern University of Science and Technologyin China for instance, created a新颖的3D打印材料这能够模仿生物组织的行为。当蜂蜜状液晶弹性体（LCE）树脂被紫外线击中时，它会固化并形成一系列薄光聚合物层的新键。
生物医学工程系的科学家Texas A&M University，创建了一个高度3D可打印的Bio-Ink. The biomaterial can be used as a platform for generating anatomical-scale functional tissues, and has been designed to overcome the structural deficiencies of current bio-inks.
New Jersey-basedRutgers Universityengineers have developed anovel bio-ink, which consists of living cells, and can be used to 3D print scaffolds for human tissue growth. The researchers were able to precisely control the material’s properties using various mixing techniques.
The researchers’ findings are detailed in their paper titled “基于水凝胶的生物键，用于组织再生中3D生物打印”发表在材料的前沿日记于2020年4月30日。这项研究由Previn Ramiah，Lisa C. du Toit，Yahya E. Choonara，Pierre P. D. Kondiah和Viness Pillay共同撰写。
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Featured image shows the submerged bioprinting technique, one of those assessed by the Witwatersrand research team. Image via Frontiers in Materials.
