The process of tissue engineering often involves the mixing of cells with polymers that may cause inflammation to the tissue and thus elevate the level of endogenous free radical production. In order to assure that such composite materials are free of genetic changes that might occur from inflammation during the development phase of the product, our laboratory is responding to the need for test methods used to assess the safety and performance of tissue-engineered materials. Specifically, we are identifying cellular biomarkers that could be used during thein vitrodevelopment phase of tissue-engineered materials to ensure that cells have not undergone any inflammatory response during the development or shipment of the product. Using GC/MS technology, we have screened for a total of five genomic modified base DNA biomarkers in tissue-engineered skin and compared the levels to control cells, neonatal fibroblasts and neonatal keratinocytes. No significant level of damage was detected compared to control cells. LC/MS technology was used in the validation of one of the oxidatively modified DNA lesions. Nearly identical results were obtained when measuring the nucleoside with LC/MS. 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.