In Vitro and In Vivo Approaches for Pre-vascularization of 3-Dimensional Engineered Tissues

  • Geraldine M. Mitchell
  • Wayne A. Morrison
Living reference work entry
Part of the Reference Series in Biomedical Engineering book series (RSBE)


A major hurdle in tissue engineering of organs is the incorporation of a functioning blood vessel network integrated throughout the engineered tissue that readily links to the surrounding host blood vessels to provide the oxygen and nutrients required by the engineered construct. In the early years of tissue engineering development, vascularization was not a priority and generally angiogenic ingrowth from neighboring host capillary networks, a process termed extrinsic vascularization was used to vascularize implanted tissue engineering constructs. Extrinsic vascularization takes weeks, and much of the implanted tissue becomes ischemic and dies before capillary ingrowth is complete. In 2000, intrinsic vascularization was devised by Tanaka et al. who isolated a macrovascular pedicle in a plastic chamber which subsequently underwent considerable angiogenic sprouting. A new arteriovenous capillary network was therefore formed within the chamber space which was capable of growing with and supporting the survival of tissue/organ specific cells implanted in the chamber. There was a time lag to development of this pedicle-based angiogenic network, and in recent years a new technique termed pre-vascularization has been developed that involves co-culture of endothelial cells with parenchymal cells or stem cells as they assemble in vitro. Capillary networks are formed throughout the construct, and upon implantation inosculate (functionally join) with host capillaries. Inosculation takes at least 2 days and provides blood flow within this time period within the construct. The most efficient vascularization technique for thick three-dimensional tissue engineering would be the combination of pre-vascularization in vitro with vascularization via angiogenic sprouting of a vascular pedicle, this combination has rarely been successfully utilized.



The authors acknowledge funding from the National Health & Medical Research Council of Australia, funding from the Australian Catholic University/O’Brien Institute Tissue Engineering Centre, the Stafford Fox Foundation Australia; the Jack Brockhoff Foundation, Australia; the Research Endowment Fund, St.Vincent’s Hospital, Melbourne, Australia; and the Victorian State Government’s Department of Innovation, Industry and Regional Development’s Operational Infrastructure Support Program.

We also acknowledge the assistance of Dr. Anne Kong, Dr. Shiang Lim, and Dr. Kiryu Yap (O’Brien Institute Department of St Vincent’s Institute, Melbourne, Australia); Dr. Guei-Sheung Liu (Centre for Eye Research Australia); Dr. Zerina Lokmic (University of Melbourne, Department of Paediatrics and Nursing, Melbourne, Australia); and Prof Shyh-Ming Kuo (Department of Biomedical Engineering, I-Shou University, Kaohsiung, Taiwan).


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Geraldine M. Mitchell
    • 1
    • 2
    • 3
  • Wayne A. Morrison
    • 1
    • 2
    • 3
  1. 1.O’Brien Institute DepartmentSt Vincent’s Institute of Medical ResearchFitzroyAustralia
  2. 2.Department of Surgery, St Vincent’s HospitalUniversity of MelbourneFitzroyAustralia
  3. 3.Health Sciences FacultyAustralian Catholic UniversityFitzroyAustralia

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