Proto-bone: an integrated protocell/matrix paradigm for prototissue calcification

原细胞是一种具有超分子区室化和信号传递等细胞活性特征的拟细胞结构。将三维原细胞集合体组装成新生的原组织提供了一个模仿高级生命系统的复杂性和结构完整性的机会，并促进了有生命材料的发展。尽管细胞与其局部细胞外基质环境之间的动态相互作用过程在多种生物活动如骨组织生物矿化中起着关键作用，但同时模拟细胞/基质相互作用的人工组织样系统尚未实现。该项目的目的是开发一种能够进行细胞外钙化的原组织模型，并形成钙化的合成组织-原骨。为了实现这一点，一个新的prototissue模型的基础上的结构和功能的整合内的一个extra-protocellular矩阵（EMT）的相互连接的合成protocells将被开发。该项目的实施将提供一种新的原组织构建模式，展示原细胞介导的骨重塑的第一个例子，并开发一种制造新的组织样矿物/基质复合材料的途径。构建具有整合的原细胞/基质组织的原组织的新方法学将为构建合成生物学中的原生命模型提供新的机会，以及开发新的仿生平台和路线，以使能够自主自我形成和退化的材料充满活力。拟议项目的成果将有助于欧洲共同体内基于材料的生物工程的发展，并可能在再生医学（组织修复，原骨植入物等）中得到长期应用。

Protocells are cytomimetic architectures that are integrated with cell-like active traits, such as supramolecular compartmentalizationand signal communication. Assembly of three-dimensional protocellular consortia into emergent prototissues provides anopportunity to mimic the complexity and structural integrity of higher-order living systems and promotes the development ofanimate materials. Although dynamic interactive processes between cells and their localized extracellular matrix environments play akey role in diverse biological activities such as bone tissue biomineralization, artificial tissue-like systems that concurrently mimic cell/matrix interactivity have not yet been achieved. The aim of the proposed project is to develop a prototissue model capable of extraprotocellularcalcification and the formation of a calcified synthetic tissue - proto-bone. To achieve this, a new prototissue modelbased on the structural and functional integration of interconnected synthetic protocells within an extra-protocellular matrix (EPM)will be developed. Implementation of the project will provide a new mode of prototissue construction, demonstrate the first exampleof protocell-mediated EPM remodeling, and develop a route to the fabrication of new tissue-like mineral/matrix composites. The newmethodology for constructing prototissues with integrated protocell/matrix organization will provide new opportunities forconstructing protoliving models in synthetic biology, as well as developing new biomimetic platforms and routes to animatematerials capable of autonomous self-formation and degeneration. Outcomes from the proposed project will contribute to thedevelopment of materials-based bioengineering within the European community, and could have long-term applications inregenerative medicine (tissue repair, proto-bone implants etc).