Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving fixed or stabilized – nonliving microorganism,...
Reexamination Certificate
1998-07-06
2001-01-09
Redding, David A. (Department: 1744)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving fixed or stabilized, nonliving microorganism,...
C435S284100, C435S287100, C073S781000, C073S790000, C073S818000, C073S813000
Reexamination Certificate
active
06171812
ABSTRACT:
FIELD OF THE INVENTION
The present invention is in the field of biotechnology and specifically relates to the study of the physiological and physiochemical processes which govern and underlie the formation, growth and resorption of human and animal bone. In particular the invention provides novel means for the study of responses of the mammalian musculoskeletal system to stress and potentially may lead to the discovery of novel substances produced by bone during these responses. The instant system may lead to a better understanding of diseases such as osteoporosis and the perfusion chamber means provides means for the study of the effects of drugs and other substances added to the perfused medium.
BACKGROUND TO THE PRESENT INVENTION—THE PRIOR ART
It has been known for over 150 years that bone responds to mechanical loading. Although the effects of exercise and mechanical loading on the musculoskeletal systems have been well documented, the actual mechanisms by which mechanical loading acts at the cellular level in the maintenance of skeletal integrity are not completely understood. Although greater attention is being given to exercise and nutrition as a means of preventing and/or treating osteoporosis, the regulatory mechanisms that control skeletal response to mechanical loading, growth factors and nutrition are not yet delineated.
There is speculation about the biophysical structure and properties of the sensory and biochemical and molecular biological mechanism of mechano-transduction. When controlled loads of a given magnitude and frequency are applied, in vivo, either in an isolated wing preparation or a rat tibia, bone mineral density is known to increase to an extent which is approximately proportional to the load applied. However, according to the prior art, it is not possible to assess quantitatively the bone-specific regulatory control product and their mechanisms nor to monitor the bone production of local growth factors and cytokines, in these in vivo preparations.
Whilst cell culture preparations do permit an investigator to quantify second messengers, cytokines and local growth factors, they do not permit one to monitor the responses of bone cells to mechanical deformation of the bone matrix which are so important in maintaining and/or remodeling of the skeletal system.
Although growth factors have been shown to enhance the development of new bone, clearly and without the presence of mechanical loading, under these circumstances, the new matrix is not formed along lines of strain and it is that feature, in life, which induces maximum integrity of the new bone so formed. The present authors have been associated with previous work in which the viability of osteoblasts from 2 to 4 week old pigs was successfully maintained, in culture, for 68 days. Careful consideration of these findings led to the hypothesis that, in a suitable novel system, which would permit continuous perfusion and mechanical loading of suitable explanted samples of trabecular bone from mature pigs, viability might be maintained for 10 to 12 days or longer. If this were to be achieved, such a time frame would permit measurements of the rate of bone formation and resorption of the trabecular bone, not available using the systems, apparatus and methods of the prior art. Further, such a novel system would be applicable to the study of human bone.
Up to now, prior art apparatus and systems for investigating bone have either comprised cell culture apparatus of a variety of well-known types or mechanical means for applying three point and four point bending forces to a biological test subject. An example of the three point type is disclosed in U.S. Pat. No. 5,406,853 to Lintilhac and Vesecky and an example of the four point type is disclosed in U.S. Pat. No. 5,383,474 to Recker and Akhter.
The present authors are not aware of any prior art system or apparatus which provides means for simultaneous, contemporaneous and continuous study of axially loaded viable mammalian bone undergoing concurrent continuous perfusion and the effluent medium therefrom.
References:
1. Baron R., Vignery A., Neff L., Silverglate A., Santa Maria A. (1983). Processing of undecalcified bone specimens for bone histomorphometry. In: ed, Recker R. R.,
Bone Histomorphometry: Techniques and Interpretation
CRC, Boca Raton, Fla., 13-35.
2. Brighton C. T., Sennett B. J., Farmer J. C., Ianotti J. P., Hansen C. A., Williams J. L., Williamson J. The inositol phosphate pathway as a mediator in the proliferative response of rat calvarial bone cells to cyclical biaxial mechanical strain. J. Orthop. Res. 10:385-393; 1992.
3. Carvalho R. S., Scott J. E., Suga D. M., Yen E. H. K. Stimulation of signal transduction pathways in osteoblasts by mechanical strain potentiated by parathyroid hormone. J. Bone Min. Res. 9::999-1011; 1994.
4. Crenshaw T. D., Thomson B. M., Noble B. S., Milne J. S. and Loveridge N. Prostaglandin E2 inhibits proliferation of porcine progenitor osteoblast cells. J. Bone Min. Res. 8(1):S362, 1993.
5. Currey J. The Mechanical Adaptation of bones. Princeton N.J.: Princeton University Press, 1984.
6. Dalsky G. P., Stocke K. S., Ehsani A. A., Slatopolsky E., Lee W. C. and Birge S. J. Weight-bearing exercise training and lumbar bone mineral content in post menopausal women. Ann. Intern. Med. 108:824-828, 1988.
7. El Haj A. J., Minter S. L., Rawlinson S. C. F., Suswillo R. and Lanyon L. E. Cellular responses to mechanical loading into vitro. J. Bone Min. Res. 5:923-932, 1990.
8. Frost H. M. (1983). Bone histomorphometry: analysis of trabecular bone dynamics. In: ed, Recker R. R.
Bone Histomorphometry: Techniques and Interpretation
CRC Press, Boca Raton, Fla., 109-142.
9. Gleeson P. B., Protas E. J., Le Blanc A. D., Schneider V. S. and Evans H. J. Effects of weight lifting on bone mineral density in premenopausal women. J. Bone, Min. Res. 5:153-157, 1990.
10. Hock J. M., Centrella M. and Canalis E. Insulin-like growth factor I (aIGF-1) has independent effects on bone matrix formation and cell replication. Endocrin. 122:254-260; 1988.
11. Hsieh H-J., Li N. Q., Frangos J. A. Shear stress increases endothelial platelet-derived growth factor mRNA levels. Am. Physiol J. 260:H642-646; 1991.
12. Jones D. B., Nolte H., Scholubbers J. G., Turner E., Veltel D. Biochemical signal transduction of mechanical strain in osteoblast-like cells. Biomaterials. 12:101-110; 1991.
13. Lanyon L. E. Control of bone architecture by functional load bearing. J. Bone Min. Res. 7:S369-S375, 1992.
14. Murray D. W. and Rushton N. The effect of strain on bone cell prostaglandin E2 release: a new experimental method. Calcif. Tissue Int. 47:35-39, 1990.
15. Mundy G. R. Bone resorbing cells. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Favus M. J. (ed), Kelseyville, Calif. American Society for Bone and Mineral Research (PP.18-22) 1990.
16. Notelovitz M., Martin D., Tesar R., Khan F. Y., Probart C., Fields C. and McKenzie L. Estrogen therapy and variable resistance weight training increase bone mineral in surgically menopausal women. J. Bone Min. Res. 6:583-590, 1991.
17. Parfitt A. M., Drezner M. K., Glorieux F. H., Kanis J. A., Malluche H., Meunier P. J., Ott S. M., Recker R. R. (1987). Bone histomorphometry: standardization of nomenclature, symbols and units. J. Bone Min. Res. 2:595-609.
18. Parfitt A. M., Mathews C. H. E., Villanueva A. R., Kleerekoper M., Frame B., Rao D. S. (1983). Relationships between surface, volume and thickness of iliac trabecular bone in aging and in osteoporosis. J Clin Inv 72:1396-1409.
19. Pead M. J., Suswillo R., Skerry, Vedi S., Lanyon L. E. Increased [3H]uridine levels in osteocytes following a single short period of dynamic bone loading in vivo. Calcif. Tissue Int. 43:92-96; 1988.
20. Parfitt A. M. The physiologic and clinical significance of bone histomorphometric data. In: Bone Histomorphometry: Techniques and interpretation. Recker R. R. (ed) (PP.143-223) 1983.
21. Raab D. M., Crenshaw T. D., Kimmel D. B., Smith E. L. A histomorphometric study of cortical bone activity during incr
Jones David
Smith Evertt L.
Lathrop & Clark LLP
Redding David A.
The National Institute of Biogerontology, Inc.
LandOfFree
Combined perfusion and mechanical loading system for... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Combined perfusion and mechanical loading system for..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Combined perfusion and mechanical loading system for... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2553355