A 3-Layered Bioartificial Blood Vessel with Physiological Wall Architecture Generated by Mechanical Stimulation.
Florian HelmsSkadi LauThomas AperSarah ZippuschMelanie KlingenbergAxel HaverichMathias WilhelmiUlrike BöerPublished in: Annals of biomedical engineering (2021)
The generation of cellularized bioartificial blood vessels resembling all three layers of the natural vessel wall with physiological morphology and cell alignment is a long pursued goal in vascular tissue engineering. Simultaneous culture of all three layers under physiological mechanical conditions requires highly sophisticated perfusion techniques and still today remains a key challenge. Here, three-layered bioartificial vessels based on fibrin matrices were generated using a stepwise molding technique. Adipose-derived stem cells (ASC) were differentiated to smooth muscle cells (SMC) and integrated in a compacted tubular fibrin matrix to resemble the tunica media. The tunica adventitia-equivalent containing human umbilical vein endothelial cells (HUVEC) and ASC in a low concentration fibrin matrix was molded around it. Luminal seeding with HUVEC resembled the tunica intima. Subsequently, constructs were exposed to physiological mechanical stimulation in a pulsatile bioreactor for 72 h. Compared to statically incubated controls, mechanical stimulation induced physiological cell alignment in each layer: Luminal endothelial cells showed longitudinal alignment, cells in the media-layer were aligned circumferentially and expressed characteristic SMC marker proteins. HUVEC in the adventitia-layer formed longitudinally aligned microvascular tubes resembling vasa vasorum capillaries. Thus, physiologically organized three-layered bioartificial vessels were successfully manufactured by stepwise fibrin molding with subsequent mechanical stimulation.
Keyphrases
- endothelial cells
- high glucose
- tissue engineering
- single cell
- platelet rich plasma
- cell therapy
- highly efficient
- reduced graphene oxide
- stem cells
- oxidative stress
- computed tomography
- cardiovascular disease
- magnetic resonance
- diabetic rats
- type diabetes
- drug induced
- signaling pathway
- wastewater treatment
- cell death
- vascular endothelial growth factor
- nlrp inflammasome
- wound healing