Cellular Biomarkers Used to Detect Damage in Tissue-Engineered Medical Products
Tissue engineering is an emerging new area of biotechnology that will provide replacement tissues for patients, as well as complex, functional biological systems for research and testing in the pharmaceutical industry. However, a lack of a formal regulatory framework has the potential for creating differences in the marketplace for products where there is no scientific basis, thereby leading to inappropriate competitive disadvantages for some products.A new research area of tissue engineering involves the investigation of how living cells interact and respond to synthetic biomaterial surfaces. The clinical development underlying such scientific research includes a number of novel tissue-engineered products. Examples include replacement skin as a synthetic dermal matrix for burns patients/chronic ulcer patients, nerve guidance channels to enhance repair of damaged peripheral nervous tissue or suitable material for the design of 'second generation' coronary artery stents for patients with heart disease. Fundamentals to many tissue-engineered devices are problems of inflammation associated with how biological cells respond to a given device when inserted into the body. Accurate measurement technologies and unique biomarkers will be needed to investigate the cellular mechanisms of how cells react to inflammatory stimuli from different polymer matrices.Thus, it is important to have biological safety check points in place during the manufacturing process of these products. To assure that tissue-engineered materials are free of molecular changes that could occur during the in vitro development phase, cellular biomarkers are being identified that can be used during the manufacturing process. Biomarkers include oxidative damage to genomic DNA by free radicals (a marker of inflammation), mitochondrial damage, genomic point mutations, and chromosomal loss.Another area of research where the use of biomarkers of cellular damage can be applied is in the area of cryopreservation. Biomarkers can be used as endpoints to monitor any genetic damage that could occur upon the preservation of cells and whether novel compounds designed to minimize damage from freezing/storing are effectively working at the molecular level.Recently, our laboratory has implemented the use of cellular biomarkers that can be used in the field of tissue engineering. Specifically, the biomarkers consist of quantifying the level of oxidative DNA damage that is a marker of cellular inflammation, screening for DNA point mutations in the p53 gene, determining the loss of the Y-chromosome that is associated with certain types of cancers, and determining the level of the mitochondrial common deletion (4977 bp), a marker associated with mitochondrial inflammation.Biomarker programs such as this can provide the basis for an international reference standard of cellular biomarkers that can aid in the development and safety of tissue-engineered medical products.