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Background: Tissue-engineered products are usually composed of living cells and their supporting matrices that have been grown in vitro, using a combination of engineering and life sciences principles. Apligraf is a bilayered product composed of neonatal-derived dermal fibroblasts and keratinocytes, and Type I bovine collagen., Objective: To evaluate in a prospective, multicentered open study, the effects of tissue therapy with a tissue-engineered skin (Apligraf) with partial or full-thickness excisional wounds., Methods: One hundred and seven patients participated in this study. The tissue-engineered skin was applied once, immediately after excisional surgery, usually for skin cancer, and patients were followed for up to one year., Results: The safety results were impressive, with no clinical or laboratory evidence of rejection. Clinically, graft persistence was good to excellent in 77 of 105 (73.3%) of patients at one week, falling to 56.6% and 53.6% at two weeks and one month respectively., Conclusion: To date, this is the largest experience with a tissue-engineered skin product in acute wounds, and this study suggests that tissue therapy may be safe and useful.

Herpes simplex virus (HSV), which was partially resistant to the inhibitory effect of disodium phosphonoacetate (PAA), could be recovered following four virus passages in the presence of 100 microgram/ml PAA. Resistant strains were isolated from both HSV type 1 and HSV type 2. Virus resistance to PAA was not complete, and in most isolations a significant proportion of the virus stock remained susceptible to the drug. Resistance was shown to be heritable and persisted through virus passage and cloning experiments. PAA inhibited the replication of virus-specific DNA in sensitive strains of HSV but not in resistant strains of HSV. In vitro experiments directly demonstrated that PAA inhibited the activity of the virus-specific DNA polymerase 10 times more effectively in PAA-susceptible HSV than in PAA-resistant HSV. The treatment of HSV-infected mice with high levels of PAA did not induce the formation of resistant virus strains.

Hematoporphyrin (HP), at concentrations as low as 0.5 microgram/ml, was found to inhibit the in vitro replication of influenza A and herpes simplex viruses, but not of several other viruses. The effect required exposure of the viruses or cells to visible light and was demonstrable when HP was administered shortly before virus inoculation or during the infection. In studies on the mechanism of action of HP, we found that in the presence of light, HP caused decomposition of GMP but not of various other nucleosides. It caused breakdown of yeast tRNA and inhibited polymerization of RNA and DNA by influenza virus and HSV-1-specific polymerases as well as some other polymerases isolated from bacterial and mammalian sources. Protective effects of HP and light were demonstrable in embryonated eggs infected with the WSN and PR8 strains of influenza A virus and in mice infected with the WSN strain. HSV-1-induced keratitis in rabbits and HSV-2-induced dermatitis in mice were not responsive to HP treatment.

The characteristics of infectious measles virus released from latently infected hamster embryo fibroblast cells are described. Low levels of virus were released spontaneously when the cultures were incubated at 37 C; this phenomenon was observed 19 passages after the cells had been exposed to the virus and has continued through cell passage 45. The virus yield could be significantly increased by cocultivation of the hamster cells with BSC-1 cells or incubation of the latently infected cells at 33.5 C rather than at 37 C. Measles virus released after cocultivation demonstrated increased cytopathology in cell culture and reduced temperature sensitivity when compared to the virus released at 33.5 C. After cell passage 45, there was an increase in spontaneous release of virus. However, the viruses recovered by cocultivation or temperature release after cell passage 45 were nearly identical. These observations suggest a possible mechanism for measles virus activation in cells latently infected with this virus.