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 Tissue engineered blood vessels and apparatus for their manufacture

Details
Inventors: McAllister, Todd N.; L'Heureux, Nicolas;
Assignee: Cytograft Tissue Engineering, Inc. (Novato, CA)
Primary Examiner: Barrett; Thomas
Assistant Examiner:
Attorney, Agent or Firm: Fish & Richardson P.C.

The invention is a tissue engineered blood vessel (TEBV) made from a cultured fibroblast sheet rolled into a multilayer vessel which has sufficient burst strength to withstand physiological blood pressure without the inclusion of smooth muscle cells or synthetic scaffolding. The TEBV is made in a bioreactor having an enclosed chamber, a sheet growth module, a rollable mandrel, and a clamp for holding the sheet to the mandrel for rolling.

DETAILED DESCRIPTION The first step in the process of making the TEBV of this invention is to prepare a sheet of fibroblasts.
This sheet includes fibroblasts taken from the patient's own body (an autologous graft) or from donor tissue (an allograft).
Allograft tissues have the advantage of being able to treat many patients from a single donor source.
However the cells used in allograft tissue must be treated to eliminate physiological foreign body responses.
This treatment typically includes removing surface antigens such that host antibodies cannot label the cells for destruction.
This can be accomplished chemically or enzymatically.
In a preferred embodiment of the invention, autologous cells are harvested from the patient's own body to eliminate the risks of disease transmission and tissue rejection.
Nearly all tissue biopsies contain some endothelial cells and some fibroblasts.
Therefore, almost any biopsy procedure or tissue harvest will provide a suitable starting point for both.
Skin or blood vessels are the best tissue sources.
The skin biopsy is accomplished, as is well known in the art, by harvesting from a patient a small patch of skin and fat, and then isolating the endothelial cells from the capillaries and the fibroblasts from the dermis.
Blood vessel biopsies can be taken by removing a small segment of a peripheral vein or artery, preferably a jugular vein (or similar superficial vessel).
Alternatively, a small segment can be harvested endoscopically (via a catheter) or by dissecting out a deep vessel.
Mesothelial cells harvested from fat can be used in place of endothelial cells.
Once a suitable biopsy is taken, fibroblasts must be isolated and expanded to obtain purified cultures.
However, reasonably low levels of other cell types may exist in the purified cultures.
Fibroblasts can be isolated from the biopsy by several different well-known techniques.
The easiest is manual dissection of skin or blood vessels to separate the fibroblast-containing tissue.
For skin biopsies, the dermis must be isolated, taking care to remove hair follicles which are a source of keratinocyte contamination



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