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胶原和弹性蛋白类似物制备的去细胞血管移植物。

Acellular vascular grafts generated from collagen and elastin analogs.

机构信息

Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

出版信息

Acta Biomater. 2013 Sep;9(9):8067-74. doi: 10.1016/j.actbio.2013.05.024. Epub 2013 Jun 3.

Abstract

Tissue-engineered vascular grafts require long fabrication times, in part due to the requirement of cells from a variety of cell sources to produce a robust, load-bearing extracellular matrix. Herein, we propose a design strategy for the fabrication of tubular conduits comprising collagen fiber networks and elastin-like protein polymers to mimic native tissue structure and function. Dense fibrillar collagen networks exhibited an ultimate tensile strength (UTS) of 0.71±0.06 MPa, strain to failure of 37.1±2.2% and Young's modulus of 2.09±0.42 MPa, comparing favorably to a UTS and a Young's modulus for native blood vessels of 1.4-11.1 MPa and 1.5±0.3 MPa, respectively. Resilience, a measure of recovered energy during unloading of matrices, demonstrated that 58.9±4.4% of the energy was recovered during loading-unloading cycles. Rapid fabrication of multilayer tubular conduits with maintenance of native collagen ultrastructure was achieved with internal diameters ranging between 1 and 4mm. Compliance and burst pressures exceeded 2.7±0.3%/100 mmHg and 830±131 mmHg, respectively, with a significant reduction in observed platelet adherence as compared to expanded polytetrafluoroethylene (ePTFE; 6.8±0.05×10(5) vs. 62±0.05×10(5) platelets mm(-2), p<0.01). Using a rat aortic interposition model, early in vivo responses were evaluated at 2 weeks via Doppler ultrasound and CT angiography with immunohistochemistry confirming a limited early inflammatory response (n=8). Engineered collagen-elastin composites represent a promising strategy for fabricating synthetic tissues with defined extracellular matrix content, composition and architecture.

摘要

组织工程血管移植物的制造时间较长,部分原因是需要来自多种细胞来源的细胞来产生具有强大负载能力的细胞外基质。在此,我们提出了一种制造包含胶原纤维网络和弹性蛋白样聚合物的管状导管的设计策略,以模拟天然组织的结构和功能。密集的纤维状胶原网络表现出 0.71±0.06 MPa 的极限拉伸强度 (UTS)、37.1±2.2%的破坏应变和 2.09±0.42 MPa 的杨氏模量,与天然血管的 UTS 和杨氏模量分别为 1.4-11.1 MPa 和 1.5±0.3 MPa 相比具有优势。在矩阵卸载过程中恢复能量的恢复力表明,在加载-卸载循环过程中,58.9±4.4%的能量得到恢复。通过快速制造具有保持天然胶原超微结构的多层管状导管,实现了内径在 1 至 4mm 之间的快速制造。顺应性和爆裂压力分别超过 2.7±0.3%/100mmHg 和 830±131mmHg,与膨体聚四氟乙烯(ePTFE;6.8±0.05×10(5) vs. 62±0.05×10(5)个血小板 mm(-2))相比,血小板黏附显著减少(p<0.01)。通过大鼠主动脉间置模型,在 2 周时通过多普勒超声和 CT 血管造影术进行早期体内反应评估,并通过免疫组织化学证实了有限的早期炎症反应(n=8)。基于胶原-弹性蛋白的工程复合材料代表了一种有前途的策略,用于制造具有定义的细胞外基质含量、组成和结构的合成组织。

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