Malda Jos, Klein Travis J, Upton Zee
Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
Tissue Eng. 2007 Sep;13(9):2153-62. doi: 10.1089/ten.2006.0417.
Oxygen is a potent modulator of cell function and wound repair in vivo. The lack of oxygen (hypoxia) can create a potentially lethal environment and limit cellular respiration and growth or, alternatively, enhance the production of the specific extracellular matrix components and increase angiogenesis through the hypoxia-inducible factor-1 pathway. For the in vitro generation of clinically relevant tissue-engineered grafts, these divergent actions of hypoxia should be addressed. Diffusion through culture medium and tissue typically limits oxygen transport in vitro, leading to hypoxic regions and limiting the viable tissue thickness. Approaches to overcoming the transport limitations include culture with bioreactors, scaffolds with artificial microvasculature, oxygen carriers, and hyperbaric oxygen chambers. As an alternate approach, angiogenesis after implantation may be enhanced by incorporating endothelial cells, genetically modified cells, or specific factors (including vascular endothelial growth factor) into the scaffold or exposing the graft to a hypoxic environment just before implantation. Better understanding of the roles of hypoxia will help prevent common problems and exploit potential benefits of hypoxia in engineered tissues.
氧气是体内细胞功能和伤口修复的强效调节剂。缺氧会营造一个潜在的致命环境，限制细胞呼吸和生长，或者通过缺氧诱导因子-1途径增强特定细胞外基质成分的产生并促进血管生成。对于临床上相关的组织工程移植物的体外生成，应考虑缺氧的这些不同作用。通过培养基和组织的扩散通常会限制体外的氧气传输，导致缺氧区域并限制活组织厚度。克服传输限制的方法包括使用生物反应器培养、具有人工微血管的支架、氧载体和高压氧舱。作为一种替代方法，可以通过将内皮细胞、基因修饰细胞或特定因子（包括血管内皮生长因子）整合到支架中，或者在植入前将移植物暴露于缺氧环境来增强植入后的血管生成。更好地理解缺氧的作用将有助于预防常见问题并利用缺氧在工程组织中的潜在益处。
