Zisch Andreas H, Lutolf Matthias P, Hubbell Jeffrey A
Institute for Biomedical Engineering and Department of Materials Science, Swiss Federal Institute of Technology Zurich (ETHZ), Moussonstrasse 18, 8044 Zurich, Switzerland.
Cardiovasc Pathol. 2003 Nov-Dec;12(6):295-310. doi: 10.1016/s1054-8807(03)00089-9.
The development of new therapeutic approaches that aim to help the body exert its natural mechanisms for vascularized tissue growth (therapeutic angiogenesis) has become one of the most active areas of tissue engineering. Through basic research, several growth factor families and cytokines that are capable to induce physiological blood vessel formation have been identified. Indeed, preclinical and clinical investigations have indicated that therapeutic administration of angiogenic factors, such as the prototypic vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF), to sites of ischemia in the heart or the limb can improve regional blood flow. For new and lasting tissue vascularization, prolonged tissue exposure to these factors could be critical. Furthermore, as shown for VEGF, dosage must be tightly controlled, as excess amounts of VEGF can cause severe vascular leakage and hypotension. This review emphasizes natural and synthetic polymer matrices with respect to their development as vehicles for local and controlled delivery of angiogenic proteins, such as VEGF and bFGF, and their clinical applicability. In the dawn of experimental vascular engineering, new biomaterial schemes for clinical growth factor administration that take better account of biological principles of angiogenic growth factor function and the cell biological basis necessary to produce functional vasculature are evolving. Alongside their base function as protective embedment for angiogenic growth factors, these new classes of bioactive polymers are engineered with additional functionalities that better preserve growth factor activity and more closely mimic the in vivo release mechanisms and profiles of angiogenic growth factors from the extracellular matrix (ECM). Consequently, the preparation of both natural or completely synthetic materials with biological characteristics of the ECM has become central to many tissue engineering approaches that aim to deliver growth factors in a therapeutically efficient mode. Another promising venue to improve angiogenic performance is presented by biomaterials that allow sequential delivery of growth factors with complementary roles in blood vessel initiation and stabilization.
旨在帮助身体发挥其促进血管化组织生长的天然机制（治疗性血管生成）的新治疗方法的开发，已成为组织工程中最活跃的领域之一。通过基础研究，已鉴定出几种能够诱导生理性血管形成的生长因子家族和细胞因子。实际上，临床前和临床研究表明，向心脏或肢体的缺血部位治疗性给药血管生成因子，如典型的血管内皮生长因子（VEGF）或碱性成纤维细胞生长因子（bFGF），可以改善局部血流。对于新的持久组织血管化，使组织长时间暴露于这些因子可能至关重要。此外，如VEGF所示，剂量必须严格控制，因为过量的VEGF会导致严重的血管渗漏和低血压。本综述着重介绍天然和合成聚合物基质，涉及它们作为血管生成蛋白（如VEGF和bFGF）局部和可控递送载体的开发及其临床适用性。在实验性血管工程的开端，考虑到血管生成生长因子功能的生物学原理和产生功能性脉管系统所需的细胞生物学基础的用于临床生长因子给药的新生物材料方案正在不断发展。除了作为血管生成生长因子的保护性包埋的基本功能外，这些新型生物活性聚合物还具有额外的功能，能更好地保持生长因子活性，并更紧密地模拟血管生成生长因子从细胞外基质（ECM）的体内释放机制和特征。因此，制备具有ECM生物学特性的天然或完全合成材料，已成为许多旨在以治疗有效方式递送生长因子的组织工程方法的核心。另一个改善血管生成性能的有前景的途径是由生物材料提供的，这些生物材料允许顺序递送在血管起始和稳定中具有互补作用的生长因子。
