Generation of 3D Bioprinted Gradient, Chiral, and Stimuli-Responsive Nanocomposite Hydrogelsas Multifunctional Biomaterials for Cell-Biomaterial Interaction Studies

组织工程学的目标是产生能够模拟自然组织的3D解剖几何和功能的生物材料。在这方面，3D生物打印得到了很大的关注，在3D生物打印中，生物材料基质中的细胞被打印在定义的3D结构中。然而，3D生物打印还处于早期阶段，到目前为止打印的材料性能有限。因此，需要先进的材料来实现多功能3D组织结构的3D生物制造，其在单一材料中提供自然组织属性的复杂性。这一要求对于材料来说是必不可少的，以确保对细胞-材料相互作用的真实研究接近模拟自然组织。为了超越目前3D生物打印和细胞-材料相互作用研究的技术水平，我们提出了一个具有挑战性的多学科项目，该项目利用了我们在纳米复合材料(NC)水凝胶方面的专业知识。我们的目标是创造第一个3D生物打印多功能NC水凝胶的例子。这种先进的材料将以单一、新颖、多功能的生物材料的形式制造，具有天然组织的以下特征：a)化学和物理梯度，b)机械上强大的水凝胶网络，c)明确的3D结构，d)不同梯度的连接，e)手性，f)刺激反应能力。在我们的方法中，我们将合成双功能手性刺激响应纳米材料，用于构建各自的NC水凝胶，并将其与不同的细胞一起用于制备手性纳米复合生物墨水。然后，利用我们手中的生物墨水，我们将生成具有多种功能的3D生物打印梯度、手性和刺激响应性生物材料。有了这些先进的构造，我们将同时研究所有实现的材料属性对细胞行为的影响。因此，该项目将开辟3D生物打印领域的新天地，并将对组织工程中细胞-材料相互作用的研究产生强大的影响。

Tissue engineering aims to generate biomaterials that can mimic native tissues’ 3D anatomical geometries and functions. In this respect, much attention has been given to 3D bioprinting, in which cells in a biomaterial matrix are printed in defined 3D architectures. However, 3D bioprinting is at an early stage, and the materials printed up to date have limited properties. Therefore, advanced materials are needed to realize the 3D biofabrication of multifunctional 3D tissue constructs that provide the complex nature of native tissue properties in a single material. This requirement is essential for the material to ensure the close simulation of native tissue for realistic studies of cell-material interactions. To go beyond the current state of the art in 3D bioprinting and cell-material interaction studies, here we propose a challenging and multidisciplinary project that capitalizes on our expertise in nanocomposite (NC) hydrogels. We aim to generate the first example of a 3D bioprinted multifunctional NC hydrogel. This advanced material will be fabricated with - in a single, novel, multifunctional biomaterial - the following characteristics of native tissue: a) chemical and physical gradients, b) a mechanically strong hydrogel network, c) a defined 3D architecture, d) connection of different gradients, e) chirality, and f) a stimuli-responsive capability. In our approach, we will synthesize bifunctional chiral stimuli-responsive nanomaterials, for the construction of the respective NC hydrogels, which will be used with different cells for the preparation of “chiral nanocomposite bio-inks”. Then with our bio-inks in our hands we will generate 3D bioprinted gradient, chiral and stimuli responsive biomaterials with multiple functionalities. With these advanced constructs, we will simultaneously study the impact of all implemented material properties on cell behavior. Thus, this project will open new horizons in the field of 3D bioprinting and will have a strong impact on cell-material interaction research in tissue engineering.