Fibrous scaffolds for building hearts and heart parts.

Fibrous scaffolds for building hearts and heart parts.
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DOI:
10.1016/j.addr.2015.11.020
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发表时间:
2016-01-15
影响因子:
16.1
通讯作者:
Parker KK
Parker KK
中科院分区:
医学1区
文献类型:
--
作者:
Capulli AK;MacQueen LA;Sheehy SP;Parker KK

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细胞外基质(ECM)的结构和生物化学为促进和调节组织生长、功能和修复提供了细胞指导线索。从结构的角度来看,ECM是一个支架,引导细胞自组装成不同的功能组织。ECM促进个体细胞之间和不同细胞类型之间的相互作用,并增加组织在机械动态环境中的强度和弹性。从生物化学的角度来看,调节细胞- ecm粘附的因素已经被描述,并且细胞- ecm相互作用在健康和疾病中的各个方面继续得到澄清。因此,天然ecm为组织工程支架提供了良好的设计规则。再生三维(3D)工程支架的设计是由目标ECM的结构、化学和力学决定的,以促进细胞浸润和组织发生。这可以通过聚合物组成的纳米纤维支架来实现,这些聚合物同时再现了3D ECM结构、高保真的纳米级形貌和生物活性。它们的高孔隙度、结构各向异性和生物活性为工程三维各向异性组织提供了独特的优势。在这里,我们以心脏为案例研究,并研究了ecm启发的纳米纤维支架在心脏组织工程中的潜力。我们问:我们的知识是否足够制造心脏?为了回答这个问题,我们将心肌和瓣膜组织的结构和功能特性制成表格,作为设计标准,回顾了纳米纤维制造平台,并评估了它们生产符合我们设计标准的支架的能力。我们对心脏解剖和生理的了解,以及我们制造合成ECM支架的能力已经进步到纳米纤维支架的瓣膜置换可能在短期内实现,而心肌修复需要进一步的体外和体内研究。
Extracellular matrix (ECM) structure and biochemistry provide cell-instructive cues that promote and regulate tissue growth, function, and repair. From a structural perspective, the ECM is a scaffold that guides the self-assembly of cells into distinct functional tissues. The ECM promotes the interaction between individual cells and between different cell types, and increases the strength and resilience of the tissue in mechanically dynamic environments. From a biochemical perspective, factors regulating cell-ECM adhesion have been described and diverse aspects of cell-ECM interactions in health and disease continue to be clarified. Natural ECMs therefore provide excellent design rules for tissue engineering scaffolds. The design of regenerative three-dimensional (3D) engineered scaffolds is informed by the target ECM structure, chemistry, and mechanics, to encourage cell infiltration and tissue genesis. This can be achieved using nanofibrous scaffolds composed of polymers that simultaneously recapitulate 3D ECM architecture, high-fidelity nanoscale topography, and bio-activity. Their high porosity, structural anisotropy, and bio-activity present unique advantages for engineering 3D anisotropic tissues. Here, we use the heart as a case study and examine the potential of ECM-inspired nanofibrous scaffolds for cardiac tissue engineering. We asked: Do we know enough to build a heart? To answer this question, we tabulated structural and functional properties of myocardial and valvular tissues for use as design criteria, reviewed nanofiber manufacturing platforms and assessed their capabilities to produce scaffolds that meet our design criteria. Our knowledge of the anatomy and physiology of the heart, as well as our ability to create synthetic ECM scaffolds have advanced to the point that valve replacement with nanofibrous scaffolds may be achieved in the short term, while myocardial repair requires further study in vitro and in vivo.