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

组织工程旨在生成能够模仿天然组织的三维解剖几何形状和功能的生物材料。在这方面，人们非常关注3D生物打印，其中生物材料基质中的细胞以定义的3D结构打印。然而，3D生物打印还处于早期阶段，目前打印的材料性能有限。因此，需要先进的材料来实现多功能三维组织结构的三维生物制造，从而在单一材料中提供天然组织特性的复杂性。这一要求是必不可少的材料，以确保密切模拟天然组织的细胞-物质相互作用的现实研究。为了超越3D生物打印和细胞-材料相互作用研究的当前状态，我们提出了一个具有挑战性的多学科项目，利用我们在纳米复合材料（NC）水凝胶方面的专业知识。我们的目标是生成3D生物打印多功能NC水凝胶的第一个例子。这种先进的材料将在一种单一的、新颖的、多功能的生物材料中制造，具有天然组织的以下特征：a)化学和物理梯度，b)机械强度强的水凝胶网络，c)定义的3D结构，d)不同梯度的连接，e)手性，f)刺激响应能力。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，这些水凝胶将与不同的细胞一起用于制备“手性纳米复合生物墨水”。然后，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，手性和刺激响应生物材料。有了这些先进的结构，我们将同时研究所有实现的材料特性对细胞行为的影响。因此，该项目将为生物3D打印领域开辟新的视野，并将对组织工程中的细胞-材料相互作用研究产生重大影响。

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.