Weekes Angus, Davern Jordan W, Pinto Nigel, Jenkins Jason, Li Zhiyong, Meinert Christoph, Klein Travis J
Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, Australia; School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD, Australia; Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD, Australia.
Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, Australia; School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD, Australia.
Biomater Adv. 2025 Oct;175:214346. doi: 10.1016/j.bioadv.2025.214346. Epub 2025 May 12.
Biofabrication techniques represent a promising avenue for the production of small diameter vascular grafts. However, while current tissue-engineered vascular grafts (TEVGs) fulfil certain functional requirements of native blood vessels, most exhibit very poor mechanical compliance, directly reducing patency in vivo. Here, highly compliant TEVGs were cultured in a dynamic pulsatile bioreactor which ensured enhanced compliance, using biomimetic melt electrowritten (MEW) tubular scaffolds as substrates for tissue growth. Through 6-week in vitro culture, we investigated differences in extracellular matrix (ECM) production and mechanical performance of TEVGs cultured with placental mesenchymal stem cells (MSCs) and smooth muscle cells (SMCs) in static and dynamic conditions. Pulsatile stimulation successfully maintained the high compliance (12.4 ± 0.8 % per 100 mmHg) of our biomimetic scaffolds, substantially greater than existing small diameter grafts. Dynamic TEVGs demonstrated physiologically relevant burst pressure (1125 ± 212 mmHg) and suture pull-out force (3.0 ± 0.4 N), while also accumulating greater ECM components than static TEVGs. To assess off-the-shelf suitability, grafts were decellularized and lyophilised to produce d-TEVGs, which exhibited negligible loss of mechanics or ECM integrity. Finally, rehydrated d-TEVGs were seeded with endothelial cells in vitro, with an intimal endothelial lining forming after 7 days. These findings demonstrate the production of TEVGs with specifically engineered mechanical compliance which has been maintained by dynamic in vitro culture, supporting continued work toward biofabrication of the next generation of vascular grafts.
生物制造技术是生产小直径血管移植物的一条有前景的途径。然而，尽管目前的组织工程血管移植物（TEVG）满足了天然血管的某些功能要求，但大多数移植物的机械顺应性很差，直接降低了体内通畅率。在此，使用仿生熔体电写（MEW）管状支架作为组织生长的底物，在动态搏动生物反应器中培养高度顺应性的TEVG，该反应器可确保增强顺应性。通过6周的体外培养，我们研究了在静态和动态条件下，用胎盘间充质干细胞（MSC）和平滑肌细胞（SMC）培养的TEVG在细胞外基质（ECM）产生和机械性能方面的差异。搏动刺激成功维持了我们仿生支架的高顺应性（每100 mmHg为12.4±0.8%），大大高于现有的小直径移植物。动态TEVG表现出生理相关的爆破压力（1125±212 mmHg）和缝线拔出力（3.0±0.4 N），同时也比静态TEVG积累了更多的ECM成分。为了评估现成的适用性，将移植物脱细胞并冻干以生产脱细胞TEVG（d-TEVG），其力学性能或ECM完整性损失可忽略不计。最后，在体外将再水化的d-TEVG接种内皮细胞，7天后形成内膜内皮衬里。这些发现证明了通过动态体外培养维持特定工程化机械顺应性的TEVG的生产，支持了下一代血管移植物生物制造的持续研究工作。
