组织工程有望实现革命性*的治疗，不过，尽管如此，它仍面临着一些有关的细胞在体外培养的关键问题。具体来说，获得在实验室培养条件而准确地模仿在体内的生长条件是要解决的关键挑战之一。

在这些情况下，再现一个“人造”血管系统能够提供充足的氧气和营养给细胞生长，以及带走细胞的新陈代谢产生的废物，是zui困难的问题之一。

在三维支架上进行细胞的培养还是我们要去面对的。假设在开始培养时氧气和营养物质均匀的分布在整个支架，细胞以相同的速度在整个支架上生长。然而，这些位于支架中心的细胞需要氧气和营养物质，二氧化碳和废物发热带走，因为相比细胞的新陈代谢，被动的交换更新的速度太慢。然后，它被发现通常会导致大于1毫米支架由于缺乏血管供应的可发育细胞和母体坏死核心的外壳。

因此，改善营养运输交换在细胞群体三维体外实验中至关重要的，为整个支架（灌注）培养介质施加一定的流速已经实验证明非常有效的比静态培养。

同样，流体刺激对某些种类的组织，例如，血管组织适当的发展也至关重要。在这种情况下，内膜层内皮细胞​​的强烈影响血流量的作用，在一般情况下，整个管路的流动已被实验证明施加的强烈影响这些细胞的行为。因此，血管流量条件下的培养是至关重要的，因为没有其他条件，更好地重现细胞在体内所经历的条件。

软骨

Lin et al. Chondrocytes culture in three-dimensional porous alginate scaffolds enhanced cell proliferation, matrix synthesis and gene expression. J Biomed Mater Res A 88 （2009） 23-33.

Raimondi et al. Engineered cartilage constructs subject to very low regimes of interstitial perfusion. Biorheology 45 （2008） 471-478

Wendt et al. Uniform tissues engineered by seeding and culturing cells in 3D scaffolds under perfusion at defined oxygen tensions. Biorrheology 43 （2006） 481-488

Mahmoudifar et al. Effect of seeding and bioreactor culture conditions on the development of human tissue-engineered cartilage. Tissue Engineering 12 （2006） 1675-1685

骨

Grayson et al. Engineering anatomically shaped human bone grafts. PNAS （2009）

Fröhlich et al. Bone grafts engineered from human adipose-derived stem cells in perfusion bioreactor culture. Tissue Eng A （2009）

Du et al. Oscillatory perfusion of CaP-based tissue engineered bone with and without dexamethasone. Annals of Biomedical Engineering 37 （2009） 146-155

Bernhardt et al. Proliferation and osteogenic differentiation of human bone marrow stromal cells on alginate-gelatine-hydroxyapatite scaffolds with anisotropic pore structure. Journal of Tissue Engineering and Regenerative Medicine 3 （2009） 54-62

血管

Bjork et al. Transmural flow bioreactor for vascular tissue engineering. Biotechnol Bioeng 15 （2009） 1197-1206

McIlhenny et al. Linear shear conditioning improves vascular graft retention of adipose-derived stem cells by up-regulation of the α5β1 integrin. Tissue Eng A （2009）

Mertsching et al. Bioreactor technology in cardiovascular tissue engineering. Adv Biochem Eng Biotechnol （2008）

Mironov et al. Cardiovascular tissue engineering I. Perfusion bioreactors: a review. J Long Term Eff Med Implants 16 （2006） 111-130.

*

Ruel et al. A new bioreactor for the development of tissue-engineered heart valves. Annals of Biomedical Engineering 37 （2009） 674-681.

Ott et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nature Medicine 14 （2008） 213-221

Brown et al. Pulsatile perfusion bioreactor for cardiac tissue engineering. Biotechnol Prog 24 （2008） 907-920

Gulbins et al. A low-flow adaptation phase improves shear-stress resistance of artificially seeded endothelial cells. Thorac Cardiovasc Surg 53 （2005） 96-102

肝脏

Atala et al. Engineering complex tissues. Sci Transl Med 14 （2012）

Li et al. Cells and Materials for Liver Tissue Engineering. Cell Transplant （2012）

Yagi et al. Decellularized scaffold as a platform for novel regenerative therapy. Nihon Geka Gakkai Zasshi 113 （2012） 419-423

Uygun et al. Application of whole-organ tissue engineering in hepatology. Nat Rev Gastroenterol Hepatol（2012

膀胱

Yagi et al. Whole-organ re-engineering: a regenerative medicine approach in digestive surgery for organ replacement. Surg Today （2012）

Horst et al. Engineering functional bladder tissues. J Tissue Eng Regen Med （2012）

Chen et al. Tissue engineering of bladder using vascular endothelial growth factor gene-modified endothelial progenitor cells. Int J Artif Organs 34 （2011） 1137-1146

Davis et al. Construction and evaluation of urinary bladder bioreactor for urologic tissue-engineering purposes. Urology 78 （2011） 954-960.

MECHANOTRANSDUCTION  力学传导

Cicha et al. Shear stress preconditioning modulates endothelial susceptibility to circulating TNF-α and monocytic cell recruitment in a simplified model of arterial bifurcations. Atherosclerosis  207 （2009） 93-102

Kowalsky et al. oxLDL facilitates flow-induced realignment of human aortic endothelial cells. Am J Physiol Cell Physiol  295 （2008） C332-340

Cicha et al. Pharmacological inhibition of RhoA signaling prevents connective tissue growth factor induction in endothelial cells exposed to non-uniform shear stress. Atherosclerosis  196 （2008） 136-145

Friedrich et al. Podocytes are sensitive to fluid shear stress in vitro. Am J Physiol Renal Physiol 291 （2006） F856-865

细胞粘附

Fuchs et al. Flow-based measurements of von Willebrand factor （VWF） function: binding to collagen and plaet adhesion under physiological shear rate. Thrombosis Research （2009）

Pfaff et al. Involvement of endothelial ephrin-B2 in adhesion and transmigration of EphB-receptor-expressing monocytes. J Cell Sci 121 （2008） 3842-3850

Petoumenos et al. High density lipoprotein exerts vasculoprotection via endothelial progenitor cells. Journal of Cellular and Molecular Medicine （2008）

MICROFLUIDICS  微灌注

Huang et al. An integrated microfluidic cell culture system for high-throughput perfusion three-dimensional cell culture-based assays: effect of cell culture model on the results of chemosensitivity assays. Lab Chip 13 （2013）:1133-43

Kim et al. Engineering of functional, perfusable 3D microvascular networks on a chip facilitates flow-induced realignment of human aortic endothelial cells. Lab Chip 13 （2013）: 1489-1500

Xu et al. Application of a microfluidic chip-based 3D co-culture to test drug sensitivity for individualized treatment of lung cancer. Biomaterials 34 （2013）:4109-17

Yokokawa et al. A perfusable microfluidic device with on-chip total internal reflection fluorescence microscopy （TIRFM） for in situ and real-time monitoring of live cells. Biomed Microdevices 14 （2012）:791-7

细胞动态种植

Álvarez-Barreto et al. Flow Perfusion Improves Seeding of Tissue Engineering Scaffolds with Different Architectures. Annals of Biomedical Engineering, 35 （2007）: 429-442

Maidhof et al. Perfusion Seeding of Channeled Elastomeric Scaffolds with Myocytes and Endothelial Cells for Cardiac Tissue Engineering. Biotechnol. Prog. 26 （2010）: 565-572

Kock et al. Perfusion cell seeding on large porous PLA/calcium phosphate composite scaffolds in a perfusion bioreactor system under varying perfusion parameters. J Biomed Mater Res Part A: 95A （2010）: 1011–1018.