Deepak Vashishth, assistant professor of biomedical engineering, hopes that his research will eventually help curb the effects of osteoporosis, a debilitating disease that poses a major health risk for 28 million Americans, according to the National Osteoporosis Foundation. Vashishth and researchers at the Bone and Joint Center at the Henry Ford Hospital in Detroit are working to pinpoint the cause of brittle bones, which could lead to preventive diagnostic testing for osteoporosis.
Vashishth is studying the effects of aging on bones fracture properties. As people age, their bones become more brittle, which accounts for the increased number of bone fractures in the elderly. The problem lies with determining the factors that increase the stiffness of bones collagen matrix, which consequently increases fracture risk.
His attempt to solve this mystery is promising. As we age, there is an increase in the number of ribose- and glucose-induced cross-links in bone that are formed due to the reaction of sugar with the collagen in bone. This gives the bone a caramelized candy look and increases the chance of fracture, Vashishth explains. But we cannot be sure whether this increased cross-linking causes the age-related deterioration in bones fracture properties.
Vashishth and his graduate students therefore conduct aging experiments in vitro to simulate this process by incubating human bones in a ribose solution at body temperature (37 degrees Celsius). The bones are de-mineralized, leaving only collagen, which is mechanically tested to estimate stiffness. Vashishth has found a 92 percent correlation between the cross-links and collagen stiffness. The bones for the study were obtained from the National Disease Research Interchange (NDRI).
The details of what happens to the collagen are tricky. As bones age, they accumulate cracks. Bone combats the propagation of such cracks into fracture by forming microcracks around a previously formed crack. Microcrack formation absorbs energy and delays the onset of fracture.
But it seems that when collagen is cross-linked, microcracks cannot form and this leaves the aging bone vulnerable to fracture.
Vashishth says that five years from now, there might be a way to break the cross-links, but he will not elaborate just yet. Its too far down the road, he says. Right now the focus is on the role of cross-links in aging bone. When we prove their role in the aging process, then we can work toward breaking them.
Hope for Sore Joints
Robert Spilker, chair of biomedical engineering at Rensselaer, heads the effort to accurately model cartilage within joints, such as the knee, hip, shoulder, and spine, that could lead to a diagnostic tool for osteoarthritis and could make many hip replacements obsolete.
Spilker and his colleagues simulate a functional environment such as the knee through computer modeling that can recreate the mechanical environment, or stress, seen by a tissue and its individual cells.
Contrary to what researchers have thought, cartilage is not homogenous, which is why it has been so difficult for tissue-engineered cartilage to work in simulated human joints.
There is more to characterizing tissue than just looking at biological structure and function, said Spilker. The properties in bones and cartilage vary within themselves and also from person to person. Growing tissue such as cartilage is a major development, but making it function as a load-carrying material requires significant new engineering research.
Currently osteoarthritis can be detected only after cartilage thinning has occurred. But by this time the functional properties of the tissue have already deteriorated significantly, making effective treatment such as drug delivery more difficult. Patient-specific cartilage modeling could help physicians predict cartilage thinning.
It would work like this: algorithms would run on an image of the area in question (spine, hip, knee) to determine the actual properties of the cartilage. Then a simulation of function on that area would provide direct information on fracture risk.
This kind of accurate joint modeling not only helps in diagnosing cartilage at risk of thinning, it means more accurate, less invasive surgeries. The main reason surgeons perform hip replacement surgery is not because of fracture but because the cartilage between the joints in the hip wears away, which causes bone to grind painfully against bone. Physicians could choose cartilage replacement surgery over hip replacement surgery in these instances if discovered in time, although Spilker admits the option might be 10 years down the road.
The challenge lies in creating patient-specific models, which requires massive computer resources. Its essential that we be able to validate our models if surgeons are to use them, Spilker explains. Spilkers goal is to make the process quick and easy.
Spilker says that there has been an increase in the number of centers looking at functional tissue engineering and that each one has a focus. Rensselaers unique ability falls into computer modeling and simulation. We dont grow the cartilage, but were the ones who will help to make it function, says Spilker.
Spilker and his team are collaborating with researchers at the Orthopedic Research Laboratory at Columbia University.
There is more to atherosclerosis than meets the eye, and Natacha DePaola is trying to find out exactly how fluid dynamics contributes to the disease.
Buildup that leads to plaque is the simplest explanation for blocked arteries. But DePaola, associate professor of biomedical engineering and a 1996 NSF CAREER award winner, and her collaborators at the University of Pennsylvania know that the mechanical and physical environments in the cardiovascular system play a crucial role in helping the disease take hold. DePaola conducts her research with grants from the Whitaker Foundation, the National Science Foundation, and the NIH.
DePaolas groundbreaking research shows that endothelial cells, those that line the arteries, lose their ability to communicate in regions of flow disturbances. Complex flow disturbances occur in specific areas of rapid and varying shear stress on the arteries, such as near an arterial branch, bifurcation, or sharp curvature. These are the same sites where atherosclerosis originates.
In experiments that precisely model the fluid dynamic conditions of regions susceptible to atherosclerosis, DePaola observed a disruption in the normal communication and transfer of signals between neighboring cells required to maintain healthy arteries. The expression of genes involved in cell communication was also significantly altered in those experiments.
The endothelial layer also serves as the principal barrier that keeps substances and cells in the blood from being transported into the arterial wall, DePaola explains. But when the mechanical and physical environment of the arteries undergoes change, the endothelial layer loses its ability to block cholesterol and certain white blood cells called monocytes from crossing through it. Eventually, this buildup of lipids and cells underneath the endothelium causes narrowing of the arteries.
DePaolas research could have a tremendous effect not only on the understanding of the origins of atherosclerosis but also on developments in vascular surgery. The shape of replacement arteries can be planned so the generation of flow disturbances is avoided, thus preventing future buildup.
Fighting the Inevitable
Rensselaer researchers conducting research about aging are enmeshed in a hopeful battle. Their goal is not to make humans indestructible, but to ease the pain of aging.
Its a matter of maintaining a quality of life for the elderly, explains Colón. Were all looking for that magic ingredient, the one that will keep us healthy and active right to the end. Who knows whether well find it, but were certainly trying.
While scientists have yet to stop the aging process, advanced technology does allow us to remain healthier longer. Ironically its that same technology some people fear will take over humankind that many researchers rely upon for their work. Food for thought as we sit on our porches in our golden years.
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