Biomimetic dense collagen gel bioinks for automated biofabrication and 3D bioprinting

用于自动化生物制造和 3D 生物打印的仿生致密胶原蛋白凝胶生物墨水

• 批准号: RGPIN-2022-04364
• 负责人: Nazhat, Showan
• 金额: $ 2.84万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761091
• 关键词: Biomimetic; dense; collagen; gel; bioinks

Additive manufacturing and three-dimensional bioprinting technologies have recently generated much interest in developing biomaterials, such as in biofabricating tissue engineering scaffolds, medical devices, and in vitro tissue-like structures that model both healthy and diseased conditions, thus enabling high-throughput drug screening and diagnostic tools. 3D bioprinting relies on the layer-by-layer deposition of tissue specific cells incorporated into hydrogels (called bioinks) to form complex hierarchical structures that mimic the body's natural extracellular matrix. Therefore, the composition, 3D bioprintability, as well as resulting bioink structure and mechanical properties are all critical to success, and ideally these would mimic, as best as possible, the natural tissue extracellular matrix. The fibre-forming collagen type I molecule is the natural scaffolding material that exists in our body. It provides many key biological and mechanical properties to numerous tissues. When extracted from the native environment, these can form hydrogels that are able to incorporate cells and be used as scaffolds for tissue engineering. However, the printing of cell-seeded collagen-based bioinks with controlled structure and mechanical properties is challenging. Collagen-based hydrogel bioinks are restricted by their narrow printability range, where the protein structure, seeded cell viability, and bioactivity of incorporated biomolecules, all need to be tightly controlled. Also, when these collagen molecules assemble into hydrogels, they suffer from low fibrillar content and have low mechanical stiffness and strength properties, all impacting our ability to engineer stable hierarchical structures. In order to overcome these challenges, we have developed a novel approach to bioprint collagen structures through our automated gel aspiration-ejection technique. By using this process, we can generate biomimetic, dense, tissue-like collagenous matrices, which can be used as in vitro models, and as scaffolds for the potential regeneration of hard and soft tissues. The technique is also ideal for producing functionalized scaffolds by incorporating other biopolymers or bioactive glasses. We will also use our in-lab developed low temperature sol-gel processing route to synthesize a novel range of borate-based glasses and to functionalize the dense collagen bioinks. Through this, we can identify the biochemical factors that drive tissue regeneration, and to continue to develop novel technologies for biomaterials development. Therefore, the knowledge gained from this Discovery Grant Program will significantly contribute to a number of fields, such as 3D bioprinting, biofabrication and tissue engineering. It will also continue to provide a rich and diverse environment for its trainees, while serving as a platform for innovative technologies.

添加剂制造和三维生物打印技术最近对开发生物材料产生了极大的兴趣，例如生物制造组织工程脚手架，医疗设备以及类似于健康和患病的状况的体外组织样结构，从而实现高通量药物筛查和诊断工具。 3D生物打印依赖于掺入水凝胶中的组织特异性细胞的逐层沉积（称为Bioinks）形成复杂的分层结构，以模仿人体的天然细胞外基质。因此，组成，3D生物明显性以及由此产生的生物学结构和机械性能都对成功至关重要，理想情况下，这些都会尽可能地模仿天然组织外基质基质。 I型I型胶原蛋白分子是我们体内存在的天然脚手架材料。它为许多组织提供许多关键的生物学和机械性能。从天然环境中提取时，它们可以形成能够结合细胞并用作组织工程的支架的水凝胶。然而，具有控制结构和机械性能的基于细胞种子的胶原蛋白的生物互联网的印刷具有挑战性。基于胶原蛋白的水凝胶生物学受其狭窄的可打印性范围的限制，在该范围内，蛋白质结构，种子细胞活力和掺入的生物分子的生物活性都需要严格控制。同样，当这些胶原蛋白分子聚集成水凝胶时，它们的原纤维含量低并且具有低的机械刚度和强度特性，这都影响了我们设计稳定层次结构的能力。为了克服这些挑战，我们通过自动化的凝胶抽吸次注射技术开发了一种新型的生物构胶原结构方法。通过使用此过程，我们可以生成仿生，密集的，组织样的胶原式矩阵，可以用作体外模型，并用作硬性和软组织潜在再生的支架。该技术也是通过掺入其他生物聚合物或生物活性玻璃来生产功能化的支架的理想选择。我们还将使用LAB内开发的低温溶胶凝胶加工途径来合成新型的基于硼酸盐的玻璃，并使密集的胶原蛋白生物互联功能功能化。通过此，我们可以确定驱动组织再生的生化因素，并继续开发新型的生物材料开发技术。因此，从该发现赠款计划中获得的知识将极大地促进许多领域，例如3D生物打印，生物制造和组织工程。它还将继续为学员提供丰富而多样的环境，同时充当创新技术的平台。