Human dermal replacement

Hansbrough, J.F., et ah. Evaluation of a biodegradable matrix containing cultured human fibroblasts as a dermal replacement beneath meshed skin grafts on athymic mice. Surgery 1992, 111, 438-446. 

Apart from the concentrafion of sericin, its extraction method has been shown to influence cell viability, also. If compared to heat, acid, or alkaline extraction methods, urea-extracted silk sericin is linked to the lowest cell viability of L929 mouse fibroblast (Aramwit et al., 2010). Sericin can also be used to replace bovine semm in cell freezing media. It cryopreserves cells as effectively as standard freeze medium containing foetal bovine serum. This effect has been demonstrated for various cell lines including P3U1 myeloma cell line, Chinese hamster ovary CHO cells, human dermal fibroblasts, human epidermal keratinocytes, the rat phaeochromocytoma cell line PC 12 and Sf9 insect cells (Sasaki et al., 2005), human primary hepatocytes (Miyamoto et al., 2010), rat pancreatic... 

In a report on a research project quantification of extrapolation factors (Kalberlah and Schneider 1998), it is noted that extrapolation factors are intended to replace lack of knowledge by a plausible assumption, and that instimtions with responsibihty for establishing the mles must decide which level of statistical certainty, e.g., applicable for 50% or for 90% of a representative selection of substances, is desired for the selection of a standard value. It is furthermore noted that extrapolation factors are required for (1) time extrapolation, e.g., from a subchronic to a chronic duration of exposure (2) extrapolation from the LOAEL to the NAEL (3) interspecies extrapolation, i.e., from experimental animals to humans and (4) intraspecies extrapolation, i.e., from groups of persons with average sensitivity to groups of persons characterized by special sensitivity. In addition to these extrapolations, route-to-route extrapolation, e.g., oral-to-inhalation or dermal-to-oral must also be discussed. 

Various tissue constructs have been reassembled from isolated constituents, including resident cell types whose numbers have been amplified or modified in culture. A three-dimensional co-culture system for human skin keratinocytes layered upon a synthetic mesh infiltrated with dermal fibroblasts, when floated to allow contact of the uppermost keratinocytes with air, exhibits stratification and cornification remarkably similar to in vivo squamous epithelia. This reconstructed epithelial model has been recommended as an in vitro replacement for dermal corrosivity testing. It has been anticipated that this and a similar noncomified model will have application in dermal and ocular irritation testing, but thus far validation studies have yielded mixed results. Reconstructed tissues can also provide context for basic toxicological research on aberrant cellular interactions with cellular and acellular constituents, as illustrated by invasion of cancerous epithelial cells into underlying dermis of a skin equivalent model. 

Some of these polycyclic musk fragrances were also found in humans [358-360]. Consumption of fish and other food from aquatic ecosystems contaminated with PMFs can not explain the concentration in human. It is assumed that the occurrence of these lipophilic compounds in human adipose tissue or mother s milk is mainly due to dermal sorption from cosmetics and detergents [349-351]. In the future the production and use of polycyclic musk fragrances will still increase and the nitro musk compounds will be replaced by the PMFs. 

Dermal Effects. Dermal exposure to 1,1,1-trichloroethane causes reversible effects in humans, which increase from mild irritation to chemical burns as exposure duration increases. Volunteers who immersed their thumbs in beakers of undiluted 1,1,1-trichloroethane for 30 minutes reported mild burning pain after 10 minutes of exposure (Stewart and Dodd 1964). Following exposure, mild erythema and fine scaling were visible on the thumb. The scaling was easily rinsed and the erythema disappeared within 1 hour. Similar results were obtained when the entire hand was immersed in the beaker, except that the burning sensation began earlier, became more intense, and then was replaced by a feeling of cold that continued 10 minutes after exposure ended. When the subject repeatedly alternated immersion in 1,1,1-trichloroethane with exposure to air, intense cold was produced by evaporation of 1,1,1 -trichloroethane from the skin. The hand remained cold for 45 minutes after the end of exposure. 

There are two basic roles for carbohydrates in the field of skin replacement. These relate to the bilaminar nature of the skin with the dermal matrix and the cellular epidermis. The matrix is a biomechanical construct and can be made. As already described, there are collagenous and noncollagenous components in the human dermis. There is and has been a considerable amount of research to explore the roles of collagen and GAG polymers in matrix production. Indeed, this is a feature of research and reviews spanning the last two decades. The most successful commercial product is Integra, which was approved for clinical use in 1996 both in the United States and Europe. 

Musculoskeletal Effects. Musculoskeletal effects have not been observed in humans or animals after inhalation, oral, or dermal exposure to zinc or its compounds. Muscles and bones contain the highest levels of zinc, and bones are believed to serve as storage depots for zinc. It is not known whether high levels of zinc in bone might be a problem because of replacement of other minerals in the bone. 

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