Irvin S. Zubar Plastic Surgery Research Laboratory, Penn State College of Medicine, Hershey, PA 17033, USA.
Department of Surgery, Division of Plastic Surgery, Penn State Health Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA.
Stem Cell Rev Rep. 2019 Apr;15(2):218-240. doi: 10.1007/s12015-019-09877-4.
Vascularization is a major hurdle in complex tissue and organ engineering. Tissues greater than 200 μm in diameter cannot rely on simple diffusion to obtain nutrients and remove waste. Therefore, an integrated vascular network is required for clinical translation of engineered tissues. Microvessels have been described as <150 μm in diameter, but clinically they are defined as <1 mm. With new advances in super microsurgery, vessels less than 1 mm can be anastomosed to the recipient circulation. However, this technical advancement still relies on the creation of a stable engineered microcirculation that is amenable to surgical manipulation and is readily perfusable. Microvascular engineering lays on the crossroads of microfabrication, microfluidics, and tissue engineering strategies that utilize various cellular constituents. Early research focused on vascularization by co-culture and cellular interactions, with the addition of angiogenic growth factors to promote vascular growth. Since then, multiple strategies have been utilized taking advantage of innovations in additive manufacturing, biomaterials, and cell biology. However, the anatomy and dynamics of native blood vessels has not been consistently replicated. Inconsistent results can be partially attributed to cell sourcing which remains an enigma for microvascular engineering. Variations of endothelial cells, endothelial progenitor cells, and stem cells have all been used for microvascular network fabrication along with various mural cells. As each source offers advantages and disadvantages, there continues to be a lack of consensus. Furthermore, discord may be attributed to incomplete understanding about cell isolation and characterization without considering the microvascular architecture of the desired tissue/organ.
血管化是复杂组织和器官工程中的一个主要难题。直径大于 200μm 的组织不能依靠简单的扩散来获得营养物质和排出废物。因此，工程化组织的临床转化需要一个综合的血管网络。微血管的直径被描述为<150μm，但临床上它们被定义为<1mm。随着超微手术的新进展，直径小于 1mm 的血管可以吻合到受体循环中。然而，这项技术进步仍然依赖于创建一个稳定的、可接受手术操作和易于灌注的工程化微循环。微血管工程位于微制造、微流控和组织工程策略的交叉点上，这些策略利用了各种细胞成分。早期的研究集中在血管生成的共培养和细胞相互作用上，同时添加血管生成生长因子以促进血管生长。从那时起，已经利用了多种策略，利用添加剂制造、生物材料和细胞生物学的创新。然而，天然血管的解剖结构和动力学并没有得到一致的复制。不一致的结果部分归因于细胞来源，这仍然是微血管工程的一个谜。内皮细胞、内皮祖细胞和干细胞的变体都被用于微血管网络的制造，同时还有各种壁细胞。由于每种来源都有其优点和缺点，因此仍然缺乏共识。此外，不和谐可能归因于不完全了解细胞分离和特征，而不考虑所需组织/器官的微血管结构。
