Magnetically oriented tissue-equivalent and biopolymer tubes

Details Magnetically oriented tissue-equivalent and biopolymer tubes Magnetically oriented tissue-equivalent and biopolymer tubes

1998-06-23

2001-02-27

Saucier, Sandra E. (Department: 1651)

Chemistry: molecular biology and microbiology

Carrier-bound or immobilized enzyme or microbial cell;...

C435S382000, C424S422000, C424S423000, C424S426000

Reexamination Certificate

active

06194182

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to oriented tissue-equivalent and biopolymer tubes and in particular bioartificial arteries made of Type I collagen formed into tubes having collagen fibrils circumferentially oriented by a magnetic field.
BACKGROUND OF THE INVENTION
The demand for artificial blood vessels, and in particular, artificial arteries is great. This is due to the fact that over 600,000 surgical procedures involving large and small blood vessels are conducted annually.
Arteries are complex structures, as the cellular and extracellular components of the artery wall are not uniformly distributed. Rather, these cellular and extracellular components are organized into discrete layers. These discrete layers have a trilaminant structure of an intima, a media and an adventitia.
The mechanical properties of the artery wall are largely due to components of the vessel media layer. Elastin is the most extensible component of the vessel media, whereas collagen is relatively stiff. The presence of smooth muscle cells is important for two reasons. First, the smooth muscle cells synthesize the elastin and collagen present in the vessel media and second, they are capable of contraction and relaxation in response to various external stimuli including vasoactive substances in the blood and sympathetic and parasympathetic nerve impulses. These smooth muscle cells are thus an important source of structural protein that contribute directly to the strength and elasticity of the vessel wall and represent a component of variable elasticity participating in the regulation of vessel tone.
The elastin and collagen components confer a nonlinear stress-strain relationship, in which the elastic modulus of the vessel wall increases (the vessel becomes stiffer) as the vessel is distended. The importance of organization to mechanical function in the arterial wall is clearly seen when arteries are compared to veins of similar size. In arteries, the circumferentially or (helically) oriented smooth muscle cells and associated elastin and collagen of the media, provide the mechanical strength necessary to withstand the higher pressures that exists in the arterial circulation. In contrast, the media layer of a vein of similar size is reduced in thickness, contains fewer smooth muscle cells, less elastin, and lastly little circumferential orientation of smooth muscle collagen and elastin seen as in the arteries.
Several attempts have been made at creating a completely bioartificial artery. Weinberg and Bell, “A Blood Vessel Model Construction from Collagen and Cultured Vascular Cells” in
Science,
Vol. 231 (1986), pp. 397-400, reported production of an artery involving smooth muscle cells and fibroblasts in layers of reconstituted Type I collagen that approximate the laminate structure, but not the circumferential orientation of natural arteries. These vessel analogs lacked the mechanical strength necessary to withstand the stress associated with pulsatile blood flow in vivo. To increase the strength, proponents of the Weinberg and Bell approach were forced to reinforce these arteries with synthetic polymer sheaths, such as Dacron®. These bioartificial arteries exhibit a severe drawback in that biocompatability problems can ultimately lead to graft failure as reported by Langer and Vacanti, “Tissue Engineering” in
Science,
Vol 260 (1993), pp. 920-926.
The orientation of fibrils and cells in collagen has been studied. For example, Torbet and Ronziere, “Magnetic Alignment of Collagen During Self-Assembly” in
Biochem. J.,
Vol. 219 (1984), pp. 1057-1059, reported collagen fibril orientation in the presence of a magnetic field. Additionally, Guido and Tranquillo, “A Methodology for the Systematic and Quantitative Study of Cell Contact Guidance in Oriented Collagen Gels” in
Journal of Cell Science,
Vol. 105 (1993), pp. 317-331, reported that cells orient in the same direction as the oriented collagen fibrils, under the phenomenon known as “cell contact guidance”.
Despite the study of fibril and cell orientation, there remains the need to provide a tissue-equivalent tube that has mechanical properties that enable it to better withstand distension, typically associated with pulsatile blood flow in arteries, without reinforcing synthetic materials.
SUMMARY OF THE INVENTION
The present invention comprises a tissue-equivalent tube that has a cylindrical body made of a reconstituted collagen network with smooth muscle cells interspersed therein. The collagen network is comprised of fibrils that orient circumferentially within the tubular body. The cells are induced by the oriented fibrils to also orient circumferentially. The circumferential orientation of fibrils and cells is characteristic of a native artery and results in improved mechanical properties.
The tissue-equivalent tube is formed by a tubular mold having a central rod and a concentric outer member, aligned to provide a cavity between the central rod and the outer member. The mold includes a longitudinal axis, extending the length of the mold. The cavity is then filled with a solution of collagen and mammalian tissue cells. In one embodiment, the filled tubular mold is then placed into a high strength magnetic field such that the longitudinal axis of the tubular mold is substantially parallel to the direction of the magnetic field. The magnetic field orients the forming collagen fibrils normal to the direction of the magnetic field, such that the collagen fibrils are oriented circumferentially with respect to the tube.


REFERENCES:
patent: 3114372 (1963-12-01), Griset, Jr. et al.
patent: 4018906 (1977-04-01), Ostendorf
patent: 4485096 (1984-11-01), Bell
patent: 4546500 (1985-10-01), Bell
patent: 4835102 (1989-05-01), Bell et al.
patent: 4837379 (1989-06-01), Weinberg
patent: 4863668 (1989-09-01), Griffths et al.
patent: 5256418 (1993-10-01), Kemp et al.
patent: WO 89/10728 (1989-11-01), None
patent: WO 93/24155 (1993-12-01), None
patent: WO 95/20359 (1995-08-01), None
Azuma, T. et al., “A rheological approach to the architecture of arterial walls”,Japan J. Physiol.,21(1):27-47 (Feb. 1971).
Barocas, V. H. et al, “The fibroblast-populated collagen microsphere assay of cell traction force—Part 2: Measurement of the cell traction parameter”,Journal of Biomechanical Engineering,117:161-170 (May 1995).
Barocas, V. H. et al., “An anisotropic biphasic theory of tissue-equivalent mechanics: The interplay among cell traction, fibrillar network deformation, fibril alignment, and cell contact guidance”,Journal of Biomechanical Engineering119(2):137-145 (May 1997).
Barocas, V. H. et al., “Biphasic theory and in vitro assays of cell-fibril mechanical interactions in tissue-equivalent collagen gels”, inCell Mechanics and Cellular Engineering,ed. V. C. Mow, Springer-Verlag; pp. 185-209 (1994).
Bell, E. et al., “Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro”,Proc. Natl. Acad. Sci. USA,76(3):1274-1278 (Mar. 1979).
Bergel, D. H., “The dynamic elastic properties of the arterial wall”,J. Physiol.156(3):458-469 (May 1961).
Burton, A., “Relation of structure to function of the tissues of the wall of blood vessels”,Physiol. Rev.,34(4):619-642 (Oct. 1954).
Buschmann, M. D. et al., “Chondrocytes in agarose culture synthesize a mechanically functional extracellular matrix”,J. Orthop. Res.,10(6):745-758 (1992).
Carr et al., “The Effect of Low Cycle Fatigue on a Novel Synthetic Collagen Vascular Graft”Society for Biomaterials,20th Annual Meeting, Boxton, MA, p. 486 (Apr. 5-9, 1994).
Chen et al., “The Use of Collagen Polymer Tube and Fibrin Clot in Peripheral Nerve Repair”,Proceedings of the National Science Coundil, ROC,18(2):58-63 (Apr., 1994).
Dickinson, R. B. et al., “Biased cell migration of fibroblasts exhibiting contact guidance in oriented collagen gels”,Annals of Biomedical Engineering,,22(4):342-356 (1994).
Diglio, C. A. et al., “Rat cerebral microvascular smooth muscle cells in culture”,Journal of Cellular Physiology,129:131-141 (1986).
Flinn, R.A. et al. (Eds

Affiliated with

Also associated with

Rating

Magnetically oriented tissue-equivalent and biopolymer tubes does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Magnetically oriented tissue-equivalent and biopolymer tubes, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Magnetically oriented tissue-equivalent and biopolymer tubes will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2596017