Bio-HhOST: Next Generation 3D Tissue Models: Bio-Hybrid Hierarchical Organoid-Synthetic Tissues (Bio-HhOST) Comprised of Live and Artificial Cells.

Bio-HhOST？将建立生物混合材料，包括活细胞和人工细胞，在动态通信，使人工细胞可以影响活细胞的增殖，分化和功能。这将通过生产精密工程化的、微尺度的、基于液体和脂质双层的、化学区室化的人工细胞来实现，与活细胞共定位。这将由一个由生物学家、工程师、数学家和企业家组成的跨学科团队完成。人工细胞将包含功能性代谢，以及对化学刺激作出反应的能力。在环境中释放信号分子，按需调节邻近的活细胞，如在复杂的生物组织中发现的。这些新的化学可编程类器官合成组织将实现范式转变，能够阐明和控制3D组织内物理化学相互作用的复杂性，并减少药物研发中的动物使用。为了实现这些目标，我们设计了一个多阶段综合工作计划，以实现以下总体目标：创建3D组织，其中活细胞分化的空间调节由共定位（化学可编程）人工细胞决定。目标2.通过活细胞和人工细胞之间的动态通信来调节和维持这种3D组织。目标3：开发类器官合成组织行为的多层次、多方法模型。这些将应用于目标应用程序; Aim 4。评估下一代生物治疗的药物输送载体。目标5产生由不同区域形成的复杂组织，这是目前的类器官方案无法实现的。这些都为Bio-HhOST方法带来了更广泛的目标，包括：i）了解越来越逼真的3D组织模型中的细胞行为，ii）阐明疾病治疗的靶点，iii）减少药物研究中的动物使用。

Bio-HhOST?will build bio-hybrid materials that comprise living & artificial cells, in dynamic communication, such that artificial cells may influence the proliferation, differentiation and function of living cells. This will be accomplished by producing precision engineered, microscale, liquid and lipid bilayer-based, chemically compartmentalised artificial cells, co-localised with live cells. This will be done by an interdisciplinary team of biologists, engineers, mathematicians and entrepreneurs. The artificial cells will contain functional metabolisms, and the ability to respond to chemical stimuli?in the environment to release signaling molecules, on demand, to regulate the neighboring living cells, as found in complex biological tissues. These new chemically programmable organoid-synthetic tissues will enable a paradigm shift, in both ability to elucidate and control the complexity of physio-chemical interactions within 3D tissues, and reduce animal use in pharmaceutical R&D. To achieve these ambitions we have designed an integrated multistage workplan driving towards the following overarching aims:- Aim 1. Create 3D tissues where spatial regulation of living cell differentiation is determined by co-located (chemically programmable) artificial cells. Aim 2. Regulate and maintain such 3D tissues by dynamic communication between live and artificial cells. Aim 3. Develop multi-level, multi-approach models of organoid-synthetic tissues behavior. These will be applied to target applications; Aim4. Evaluating drug delivery vectors for next generation biological therapeutics. And Aim5. generation of complex tissues formed of distinct different regions, not achievable with current organoid protocols. These exemplify our wider ambitions for the Bio-HhOST approach including to, i) understand cell behavior in increasingly realistic 3D tissue models, ii) elucidate targets for the treatment of disease, and iii) enable the reduction of animal use in pharmacuetical research.