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

Bio-HhOST？将构建由活细胞和人造细胞组成的生物杂化材料，在动态交流中，人造细胞可能会影响活细胞的增殖、分化和功能。这将通过生产精密工程、微型、液体和脂类双层、化学分隔的人造细胞来实现，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来完成。人造细胞将包含功能性新陈代谢，以及对环境中化学刺激的反应能力，根据需要释放信号分子，以调节邻近的活细胞，就像在复杂的生物组织中发现的那样。这些新的化学可编程有机合成组织将在阐明和控制3D组织内物理-化学相互作用的复杂性方面实现范式转变，并减少药物研发中的动物使用。为了实现这些雄心壮志，我们设计了一个综合的多阶段工作计划，旨在实现以下主要目标：-目标1.创建3D组织，其中活细胞分化的空间调节由共处(化学可编程)人工细胞决定。目的2.通过活细胞和人工细胞之间的动态通讯来调节和维持这种3D组织。目的3.建立有机合成组织行为的多层次、多途径模型。这些将应用于目标应用程序；Aim4。评估下一代生物疗法的药物输送载体。和Aim5.产生由截然不同的不同区域形成的复杂组织，这是目前的有机体方案无法实现的。这些体现了我们对Bio-HhOST方法的更广泛的雄心，包括：i)在越来越逼真的3D组织模型中了解细胞行为，ii)阐明疾病治疗的靶标，以及iii)在药理研究中减少动物使用。

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.