Vascularization of 3-D Grafts
Dr. A. Haverich,[19] from the Hannover Medical School, Germany, illustrated the feasibility of reconstructing cardiac and venous valves by tissue engineering. This can be achieved by seeding autologous cells such as myofibroblasts and endothelial cells on a biocompatible scaffold (eg, decellularized xenogeneic valves). Preliminary results obtained in a sheep model showed that tissue-engineered venous valves grafted into native vessels (external jugular vein) were successfully repopulated by myofibroblasts and endothelial cells.[20] Tissue-engineered valves were competent at ultrasound analysis in 22 of 24 implants and were almost indistinguishable from autografts.
Another great challenge in the field of tissue and organ engineering is achieving the vascularization of 3-D grafts.[21] While cartilage is avascular and skin grafts are thin enough to pick up their blood supply from the implantation bed, the successful implantation of more complex tissue-engineered structures is hampered by the lack of satisfactory vascularization. Two main ways to create vascularized structures can be envisioned: the stimulation of the endogenous angiogenesis process and the formation of structures that mimic the vascular tree of the organ or tissue being engineered.
The first approach is being made possible by the rapidly growing knowledge on the angiogenesis processes and implies the administration of angiogenic factors. Most studies, so far, have used fibroblast growth factor and/or vascular endothelial growth factor, but it can be foreseen that use of additional factors in different combinations will be able to improve on the results obtained.
The second approach foresees the exploitation of either an extrinsic or an intrinsic blood supply. For the extrinsic blood supply, the structure to be transplanted is implanted into a rich vascular bed resulting in vascular ingrowth from the tissues surrounding the structure. Revascularization occurs through the response to surgical implantation and the subsequent inflammatory wound-healing reaction. Angiogenic growth factors expressed locally will influence the vascularization of the implanted tissue. An intrinsic blood supply, on the other hand, has the advantage that it could be generated in vitro as well as in vivo, by introducing into the tissue to be engineered either endothelial cells or fibroblasts, whose growth needs then to be stimulated, or small vascular grafts that may then be induced to form a vascular bed.
As encouraging as these results are, far more needs to be done in the future to achieve a clinical applicability of these technologies.[22,23] As noted by Mitchell and Niklason,[24] a number of requirements will have to be met by tissue grafts:
The endothelium in the graft should be confluent, adherent, and quiescent to minimize the risk of thrombosis;
The graft must mimic in vivo the mechanical properties of the native structure, a characteristic that is generally sustained by a highly organized collagen matrix; and
Reconstitution of a highly compliant elastin network is needed to ensure full graft functionality.
© 2003 Medscape
Cite this: Tissue Regeneration and Organ Repair: Science or Science Fiction? - Medscape - Jul 14, 2003.
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