Tissue engineering and regenerative medicine hold the promise of helping to heal or even replace tissues, organs, and other body structures. For this promise to be realized, continued progress will be needed in the fields of stem cell biology, cellular signaling, growth factor biology, differentiation, and engineering of biocompatible scaffolds, among others.
Obstacles RemainNadya Lumelsky is the Director of the Tissue Engineering and Dental and Craniofacial Regenerative Medicine Research program, National Institute of Dental and Craniofacial Research, National Institutes of Health (NIH), Bethesda, MD. She believes that the fields of tissue engineering, defined as in vitro generation of tissue constructs for replacement of diseased or injured host tissues, and regenerative medicine, primarily focused on in vivo strategies for tissue reconstruction, have much to learn from each other and to contribute to each other. For example, regenerative medicine needs new tools to deliver cytokines, growth factors, and other biologically active molecules to tissues at specific times, concentrations, and location. “The tissue engineers are already developing such tools,” says Lumelsky. “For instance, they have designed biologically active nanotechnology-based self-assembling and self-hardening scaffolds that can be injected at the site of injury as liquids, thereby precisely delivering needed biologically active molecules to tissues to be released with predetermined kinetics.”
Another important goal for tissue engineering as well as for regenerative medicine is generation of complex tissues, such as vascularized bone and bone-cartilage composites. Considerable progress resulting from interdisciplinary interaction between researchers working in the fields of tissue engineering and regenerative medicine has already been achieved in this area.
“For any tissue reconstruction, it is important to consider the endogenous state of the host tissue,” notes Lumelsky. “Many common diseases, such as arthritis, periodontitis, and others, are hallmarked by continuous process of tissue destruction resulting from autoimmunity, inflammation, or infection. In order to restore the healthy tissue, we need to think about overcoming these destructive processes. The tools of tissue engineering and regenerative medicine are beginning to be applied toward this goal.”
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Marjana Tomic-Canic, Department of Tissue Engineering, Repair, and Regeneration, Hospital for Special Surgery, New York, NY, is interested in the biology of wound healing. Although FDA-approved tissue-based products to promote wound healing in the skin have been available for some time, Tomic-Canic notes that the mechanobiology of skin is not clear or well studied. She and her collaborators, including Harold Brem, Wound Healing Program and Wound Healing and Vascular Biology Laboratory, Columbia University, College of Physicians and Surgeons, New York, NY, are interested in the stress and structural changes that occur when loads are applied to tissue, such as skin. “The signaling and gene expression” that occur under stress “is a black box,” she observes. Pressure sores (decubitus ulcers) that occur in people with diabetes and in bed-bound patients and the elderly seem to be vascular, she says, but there are also mechanical components. In their model system of human skin culture, Tomic-Canic and colleagues look at loads on skin and the early damage that occurs, hoping to discover what leads to the pathology that is seen in the clinic.
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“The diagnostic use of gene chip technology and molecular profiling to demarcate bad from good tissue in and around wounds is a very exciting project,” Tomic-Canic says. Standard treatment of pressure ulcers includes removal of necrotic tissue from the area, but sometimes it is difficult to tell how wide an area the debridement should include. It may be difficult to distinguish healthy from damaged cells, and histology may not be good enough. By using gene profiling, it may be possible, through detection of a recognizable pattern, to see where the nonhealing edge of the ulcer is located. Tomic-Canic says they are at the first stage, looking for molecular markers of pathology. When those markers are identified, immunohistochemistry, rather than molecular profiling, may be the ultimate clinical tool. Profiling might be used diagnostically, such as to distinguish different types of ulcers and choose the best therapy.
