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

原细胞是一种模拟细胞的结构，它整合了细胞样的活性特征，如超分子区隔和信号通讯。将三维原细胞联合体组装成新生的原组织，为模拟高级生命系统的复杂性和结构完整性提供了机会，并促进了生物材料的发展。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骨组织生物矿化等多种生物学活动中起着关键作用，但同时模拟细胞/基质相互作用的人工组织状系统尚未实现。拟议项目的目的是开发一种能够在原细胞外形成钙化和形成钙化的合成组织-原骨的原始组织模型。为了实现这一点，将开发一种新的原组织模型，该模型基于相互连接的合成原细胞在原细胞外基质(EPM)内的结构和功能集成。该项目的实施将提供一种构建原组织的新模式，展示第一个由原细胞介导的EPM重塑的例子，并为制造新的组织样矿物/基质复合材料开辟一条途径。构建具有完整原细胞/基质结构的原始组织的新方法将为构建合成生物学中的原生生物模型以及开发能够自主形成和退化的生物材料的新的仿生平台和途径提供新的机会。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).