Synthetic Vessels for Bone Tissue Engineering 
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Vascularization is one of the most important issues for creating large-scale tissue-engineered (TE) bone. The incorporation of angiogenic growth-factors into the scaffolds may be one important key. Another, more speculative approach might be to embed TE vessels directly into layers of bone scaffolding (as suggested in our Layered Manufacturing link) and anastomose the synthetic vessels to native, host vasculature. The goal is for capillaries to sprout from the embedded TE vessel into the surrounding tissue. Our group is investigating the fabrication of TE synthetic vessels suitable for embedding into layers of bone scaffold material.

Tissue engineers have sought to create synthetic vessels for grafting applications [1]. For example, our collaborator, Matsuda, has investigated creating hierarchically structured synthetic vessels for venous system applications [2]. In this approach, collagen incorporating smooth muscle cells (SMCs) is molded into tubular shapes. The SMCs cause the tubes to shrink and gain some strength. The luminal surfaces of the tubes are then seeded with endothelial cells. Thrombosis, strength, and fabrication complexity, however, are still issues. In other work, there is an evidence of capillary sprouting from collagen-based systems [3]. Bone marrow (BM) cultured in collagen gels formed short capillaries for two weeks and then capillary networks for four weeks. Other researchers fabricated Dacron seeded with bone marrow to inhibit thrombogenesis [4]. All the grafts older than three weeks had completely endothelialization and maintain their patency. Our tissue engineering group, in collaboration with Matsuda, is interested in combining the ideas described above in order to develop a practical fabrication process for making synthetic vessels.

Our approach is to prepare a double layered collagen-based system, for strength, which incorporates BM stromal cells as a rich source for vessel morphogenesis in vivo. Typical synthetic vessels manufactured with this approach, such as shown in the figure above, have dimensions of 4 mm in inner diameter, 800 mm in wall thickness and 50 mm in length. These tubes are easy to handle and to suture. Their burst strengths are approximately 80 mmHg.  Theses tubes, when protected with stiff osteogenic scaffolds, should have the potential to withstand  physiological blood pressures during the initial implantation period. We are currently preparing to conduct such in vivo studies.

References:

1. Weinberg, CB.; Bell, E. A blood vessel model constructed from collagen and cultured vascular cells. Science. 231:397-400: 1986.
2. Hirai, J.; Matsuda, T. Venous reconstruction using vascular tissue composed of vascular cells and collagen: Tissue regeneration process. Cell Transplant. 5:93-105: 1996.
3. Mori, M; Sadahira, Y.; Kawasaki, S.; Hayashi, T.; Awai, M. Formation of capillary networks from bone marrow cultured in collagen gel. Cell Struct. Funct. 14:393-398: 1989.
4. Noishiki, Y.; Tomizawa, Y.; Yamane, Y.; Matsumoto, A. Autocrine angiogenic vascular prosthesis with bone marrow transplantation. Nature Medicine. 2:1:90-93; 1996.