Capulli A K, MacQueen L A, Sheehy Sean P, Parker K K
Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
Adv Drug Deliv Rev. 2016 Jan 15;96:83-102. doi: 10.1016/j.addr.2015.11.020. Epub 2015 Dec 4.
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.
细胞外基质（ECM）的结构和生物化学特性提供了细胞指导性线索，可促进和调节组织生长、功能及修复。从结构角度来看，细胞外基质是一个支架，引导细胞自组装形成不同的功能组织。细胞外基质促进单个细胞之间以及不同细胞类型之间的相互作用，并在机械动态环境中增强组织的强度和弹性。从生物化学角度来看，调节细胞与细胞外基质黏附的因素已被描述，细胞与细胞外基质在健康和疾病状态下相互作用的多个方面仍在不断阐明。因此，天然细胞外基质为组织工程支架提供了出色的设计规则。再生三维（3D）工程支架的设计依据目标细胞外基质的结构、化学性质和力学特性，以促进细胞浸润和组织形成。这可以通过使用由聚合物组成的纳米纤维支架来实现，这些聚合物能同时重现3D细胞外基质结构、高保真纳米级形貌和生物活性。它们的高孔隙率、结构各向异性和生物活性为工程化3D各向异性组织带来了独特优势。在这里，我们以心脏为例，研究受细胞外基质启发的纳米纤维支架在心脏组织工程中的潜力。我们提出问题：我们是否具备足够的知识来构建一颗心脏？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，用作设计标准，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。我们对心脏解剖学和生理学的了解，以及创建合成细胞外基质支架的能力已经发展到这样一个程度，即短期内使用纳米纤维支架进行瓣膜置换可能实现，而心肌修复则需要在体外和体内进行进一步研究。
