Bioengineering Program, Fred DeMatteis School of Engineering and Applied Science, Hofstra University, 229 Science and Innovation Center, Hempstead, NY, 11549, USA.
Mechanical Engineering Program, Fred DeMatteis School of Engineering and Applied Science, Hofstra University, 200B Weed Hall, Hempstead, NY, 11549, USA.
Tissue Eng Regen Med. 2024 Dec;21(8):1189-1201. doi: 10.1007/s13770-024-00670-0. Epub 2024 Oct 1.
Vascular grafts are mainly composed of synthetic materials, but are prone to thrombosis and intimal hyperplasia at small diameters. Decellularized plant scaffolds have emerged that provide promising alternatives for tissue engineering. We previously developed robust, endothelialized small-diameter vessels from decellularized leatherleaf viburnum. This is the first study to precondition and analyze plant-based vessels under physiological fluid flow and pressure waveforms. Using decellularized leatherleaf viburnum as tissue-engineered grafts for implantation can have profound impacts on healthcare due to their biocompatibility and cost-effective production.
A novel perfusion bioreactor was designed, capable of accurately controlling fluid flow rate and pressure waveforms for preconditioning of small-diameter vascular grafts. A closed-loop system controlled pressure waveforms, mimicking physiological values of 50-120 mmHg at a frequency of 8.75 Hz for fluid flow reaching 5 mL/min. Plant-based vascular grafts were recellularized with endothelial and vascular smooth muscle cells and cultured for up to 3 weeks in this bioreactor. Cell density, scaffold structure and mechanics, thrombogenicity, and immunogenicity of grafts were evaluated.
Bioreactor treatment with fluid flow significantly increased luminal endothelial cell density, while pressure waveforms reduced thrombus formation and maintained viable vascular smooth muscle cells within inner layers of grafts compared to static controls. Suture retention of grafts met transplantation standards and white cell viability was suitable for vascular remodeling.
Low thrombogenicity of endothelialized leatherleaf viburnum holds great potential for vascular repair. This study provides insight into benefits of conditioning plant-based materials with hemodynamic forces at higher frequencies that have not previously been investigated.
血管移植物主要由合成材料组成，但在小直径时容易发生血栓形成和内膜增生。脱细胞植物支架已经出现，为组织工程提供了有前途的替代品。我们之前已经从脱细胞的腊叶卫矛中开发出了坚固的、内皮化的小直径血管。这是第一项在生理流体流动和压力波形下预处理和分析基于植物的血管的研究。由于其生物相容性和具有成本效益的生产，使用脱细胞腊叶卫矛作为组织工程移植物植入可以对医疗保健产生深远的影响。
设计了一种新型灌注生物反应器，能够精确控制小直径血管移植物的流体流速和压力波形。闭环系统控制压力波形，模拟生理值为 50-120mmHg 的频率为 8.75Hz 的流体流动达到 5mL/min。植物来源的血管移植物用内皮细胞和血管平滑肌细胞再细胞化，并在该生物反应器中培养长达 3 周。评估了移植物的细胞密度、支架结构和力学、血栓形成和免疫原性。
生物反应器中的流体流动处理显著增加了管腔内皮细胞的密度，而压力波形与静态对照相比，减少了血栓形成，并维持了移植物内层中的存活血管平滑肌细胞。移植物的缝线保留符合移植标准，白细胞活力适合血管重塑。
内皮化腊叶卫矛的低血栓形成性为血管修复提供了巨大的潜力。这项研究提供了在以前未研究过的更高频率下用血流动力学力预处理基于植物的材料的好处的见解。
