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Damaged cartilage in knees and joints caused by traumatic injury or the regular wear and tear of age is nearly impossible for the body to repair on its own. Unlike other tissues, cartilage lacks the blood vessels that deliver nutrients and other healing substances to damaged regions. Medical treatment usually aims to alleviate pain and discomfort without mending underlying injuries.

 

However, a newly developed liquid polymer gel that solidifies in 30 seconds when exposed to laser light could help the body use its own resources to replenish damaged cartilage. The biomaterial, which can be injected into torn cartilage tissue, adapts to the contours and size of the cartilage tear. Once cured to a solid, the polymer acts as a scaffold for the body’s own cartilage producing cells, which can eventually replace the biomaterial with new and functional cartilage.

 

 

A material developed from the small intestines of pigs has shown remarkable results in supporting the body’s own healing process. The material, called SIS (small intestinal submucosa), has been used to treat a wide variety of conditions from ligament reconstruction to incontinence in women. Today, SIS is most commonly used to help the body mend hard-to-heal wounds, such as second-degree burns, chronic pressure ulcers, and diabetic skin ulcers.

 

When magnified, SIS looks like a wild matrix of loosely intertwined collagen fibers with channels and space in between the threads. When a patch of SIS is placed over an open wound, the SIS tissue acts as an anchor for migrating cells, such as fibroblasts, that help synthesize collagen, and macrophages, which fight off bacteria. The patch also supports growing capillaries as they wrap themselves around the collagen fibers like small vines. 

 

It is not so surprising that the intestinal mucosa provides such a good platform for growing cells. The cells that line the intestine are regenerated at one of the highest rates of any cell type found in the body. The same factors that are important for rapid replacement of intestinal cells are also important for repair of other tissues. Once established, these capillaries provide oxygen and nutrients to the new tissue.

 

SIS also offers several advantages as a biomaterial. Prior to SIS, skin grafts from human cadavers were routinely used for wound closure and burn treatment. Unlike cadaver tissue, however, the porcine graft is not susceptible to human diseases and viruses, such as HIV or hepatitis. Because SIS is composed of collagen and other materials found in humans, there are no known cases of rejection, unlike with some synthetic materials.  Scientists are continuing to explore the biochemical mechanisms responsible for SIS’s success as a wound healer.

 

 

 

With technologies such as functional neuroimaging, scientists can monitor brain activity in animals or humans as they engage in a variety of activities and complex behaviors. Such studies often present a challenge, however, because subjects must be immobilized for the imaging equipment to produce a clear picture of the active brain regions.

 

NIH-supported scientists have created a miniature implantable device called a microbolus infusion pump that releases radioactive tracer molecules into the bloodstream by remote control. When implanted in rats, the pump can be activated to release the tracers just before an animal begins an activity such as running or eating. Scientists can then detect the distribution of the tracer in the brain. The pump opens the possibility of studying functional brain activity of complex behaviors involving animal movement, which has remained largely inaccessible to other brain-mapping techniques. Future studies with the pump will involve investigating animal models of human psychiatric disorders.

 

Imaging technologies that can distinguish cellular- and molecular-level components will give researchers an extremely powerful tool to diagnose, track, and treat a variety of diseases. Early research in applying optical imaging techniques to breast cancer research has shown particular promise. Because breast cancer is a molecular disease that has early-stage cellular changes, techniques that can detect these changes may offer a more precise diagnosis and more tailored treatment than do conventional techniques. High-resolution imaging offers an important new method to detect and track breast malignancies that may be difficult to distinguish on conventional mammograms.

 

One such imaging technique is optical coherence tomography (OCT), which relies on near-infrared wavelengths of light to produce an image. OCT is similar to ultrasound, but OCT uses light rather than sound waves to create an image. Light waves can penetrate only a few millimeters into breast tissue, yet the images produced from the light waves can show cellular activity as clearly as images developed from pathology slides. Because of OCT’s ability to capture images in real time, the technique may be used to rapidly scan large sections of tissue for suspicious growths; to guide, at the cellular level, surgical removal of malignancy; and to scan tumor margins for the presence of additional disease.

 

Scientists have developed a thin fiber-optic probe that may provide a rapid and accurate alternative to core needle biopsies for detecting breast malignancies. With core needle biopsies, a surgeon guides a hollow needle into the breast tissue and removes about a dozen tissue samples for analysis; the procedure has a false-negative rate of up to 7 percent. But the new fiber-optic probe can be threaded through the biopsy needle’s hollow channel to its tip and placed in the breast directly at the tumor site. The probe then emits near-infrared light into the breast tissue. By monitoring what happens to the light as it travels through the tissue, researchers obtain structural and physiological information about the tissue that indicates whether the needle has hit its mark in the malignancy.

 

Researchers survey multiple areas in the breast by simply rotating the needle, obtaining an immediate picture of malignant tissue that should be biopsied. The probe may work best when combined with another optical sensor for biopsy needles also under development. By detecting the different fluorescence properties of malignant and normal tissue, the sensor can differentiate benign and cancerous breast tissue with 90 percent accuracy in preliminary tests. Although these technologies will not eliminate biopsies, they can provide a more accurate way to locate malignant tissue and ultimately help doctors make an immediate diagnosis.

 

 

Molecular probes offer researchers a new tool to gather information about the fundamental actions and reactions that occur in cells and molecules. By using fluorescent probes that are compatible with biological material, researchers can obtain color images of cellular and molecular activity. One form of molecular probe that has generated recent interest is semiconductor nanocrystals. These microscopic particles exhibit unique optical properties that offer major advantages over conventional fluorescent dyes for imaging biological samples.

 

Nanocrystals that transmit light near the infrared (IR) region of the spectrum are especially useful for biological applications, because near-IR light penetrates deeply into body tissues and produces little of the background "noise" that can obscure a light signal. Unfortunately, some nanocrystals synthesized to emit near-IR light signals are toxic, unstable, and susceptible to light bleaching. By specially coating these light beacons, a group of scientists has found a way to suppress their toxicity, maintain and improve their ability to transmit light, and limit photobleaching. The new coatings make nanocrystals highly efficient at transmitting light in the near-IR region.

 

Another research group, using molecular beacons, has developed a simple method to measure RNA synthesis in real time. This new approach will aid in the understanding of various mechanisms that control RNA and protein production in cells. Once scaled up to high-throughput formats, the measurement of RNA synthesis will be useful in identifying new drugs that inhibit RNA production by bacteria or viruses. In addition, assays might be developed to identify an infectious agent and then quickly determine which antibiotics might be effective or ineffective against the particular strain that is present. 

 

 

A state-of-the-art imaging technique has detailed for the first time how viral DNA binds to and activates an enzyme crucial for viral replication, paving the way for research into new drugs that would fight disease by preventing such binding. The imaging method, known as synchrotron X-ray footprinting, uses high-intensity X-rays to characterize and display minute structural details of interactions between molecules.

 

NIH-supported researchers applied this technique to human adenovirus, a culprit in common respiratory, gastrointestinal, and eye infections. The scientists focused the synchrotron X-rays on an adenovirus enzyme called human adenovirus proteinase (AVP), a protease enzyme that helps the adenovirus produce new infectious virus particles. DNA from the adenovirus needs to bind to AVP in order for the enzyme to become fully active.

 

The synchrotron data revealed that the viral DNA binds to AVP over a region covering more than half the enzyme molecule, providing ample targets for drugs designed to block that binding.  The data also shed light on the molecular changes produced in the protease when it pairs up with the DNA.

 

Armed with these details, scientists have already begun searching for drugs that might treat adenovirus infections by keeping the viral DNA and AVP apart. Since AVP shares features with proteases from many other pathogens, including deadly ones such as HIV, similar imaging studies could potentially help scientists develop better drugs for a variety of serious conditions.

 

Gupta S, Mangel WF, McGrath WJ, Perek JL, Lee DW, Takamoto K, Chance MR. DNA binding provides a molecular strap activating the adenovirus proteinase. Molecular and Cellular Proteomics 3:950-959, 2004.

 

 

DNA sequencing promises to improve the way in which diseases such as cancer are diagnosed, monitored, and treated. The technology relies on detecting fluorescent signals created when pieces of DNA bind together on a microchip. An emerging technology—electrophoresis on microchips—has aided DNA sequencing by miniaturizing processing technologies. Miniaturization has reduced the time needed to analyze samples and decreased the sample size required for testing.

 

To extend the power of DNA sequencing, a research team has developed a new microscope that can identify fluorescently labeled DNA sequencing fragments that have been separated by microchip technology. Using the new microscope, researchers will gain more information from a single electrophoresis test because more fluorescent dyes can be used and detected. Researchers expect to gain additional insights into the molecular profiles of many diseases as a result of these developments.

 

Zhu L, Stryjewski WJ, Soper SA. Multiplexed fluorescence detection in microfabricated devices with both time-resolved and spectral-discrimination capabilities using near-infrared fluorescence. Anal Biochem 330:206-218, 2004.

 

 

A tiny scale that is sensitive enough to weigh a single virus particle may become the basis for biodefense detection systems that can instantly recognize dangerous viruses.  Scientists recently fabricated a microscopic, silicon-based device that looks like a tiny diving board and vibrates naturally at a particular frequency. Researchers measure the frequency by bouncing laser light off the tip of the device, known as a cantilever.  Because the cantilever is so small, about one micron wide, or approximately one-hundredth the width of a human hair, it is extremely sensitive to changes in mass, even the addition of a single virus.

 

The researchers succeeded in placing a lone particle of the vaccinia virus on the cantilever, allowing them to weigh the virus. The addition of the virus changed the vibration frequency in a measurable way, signaling a change in weight. The virus weighed in at nine femtograms, or quadrillionths of a gram. The next step in development will involve efforts to coat the cantilevers with antibodies that will allow only a single type of virus to stick to the device. This research represents a significant step toward the development of handheld systems that can detect viruses, bacteria, and other airborne microbes in real time. Such biosensors could detect bioterror agents that might be used in attacks, and may be useful for other purposes, such as monitoring air quality in hospitals.