Biomedical Engineering Reference
In-Depth Information
'any procedure that involves the transplantation, implantation or infusion into a
human recipient of either (a) live cells, tissues or organs from a non-human animal
source, or (b) human body fluids, cells, tissues or organs that have had
ex vivo
contact with live non-human animal cells, tissues or organs'.
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Feeder layer cells
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irraditated to render them non-proliferative for use in co-cultures are considered to
be living and thus, within the definition of xenotransplantation. To avoid the
potential risks associated with xenotransplantation, alternative methods of im-
proving attachment and proliferation of freshly isolated cells have been used,
including using culture vessels coated with extracellular matrix proteins.
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CSS
consist of cells attached to a biodegradable polymer and are currently regulated in
the United States as class III (significant risk) medical devices, with rigorous
requirements for demonstration of safety and efficacy and compliance with good
manufacturing practices (GMPs). Thus efforts are made continually to improve
laboratory practices to comply with prevailing FDA guidelines.
12.7 Future trends
Much progress has been made by the combined efforts of biologists, chemists,
geneticists, bioengineers and materials engineers to develop a permanent substi-
tute for human skin. However, current models of skin fail to replicate all of the
structures and functions of normal human skin. Improvements to the design of
future models of skin substitutes are likely to include alternative scaffolding
materials, addition of cellular components (e.g. melanocytes for pigmentation,
endothelial cells for vascularization), biologic regulation of wound healing and
genetic modification of transplanted cells.
12.7.1 Improving mechanical strength of cultured skin
substitutes
Shear and maceration of cultured skin grafts is an important source of CSS failure.
Thus improving the mechanical strength of the CSS prior to grafting may result in
increased rates of engraftment. Collagen-GAG scaffolds have been tested for
maximum load at failure and have <1% failure loads compared to split-thickness
autografts.
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Improving the mechanical stability and strength of the acellular
collagen scaffold is one strategy for increasing the strength and stability of the CSS.
Cross-linking collagen scaffolds via chemical methods has been widely utilized to
slow degradation rates and optimize mechanical properties. Historically, glutaral-
dehyde (GA) has been the most widely utilized chemical cross-linking reagent.
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However, GA cross-linked biomaterials have been reported to exhibit reduced
cellular ingrowth
in vitro
and
in vivo
,
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thus alternative reagents have been
employed. To overcome reagent toxicity, carbodiimides have been used to cross-
link collagen because they are members of the zero-length class of cross-linkers.
Cross-linking collagen-GAG sponges used to fabricate CSS has been shown
