A rapidly fabricated dermal equivalent.
Doctoral thesis, UCL (University College London).
Cell encapsulation in collagen hydrogels affords the ability to rapidly create living yet mechanically weak tissue equivalents. A previously developed compression technique that removes the interstitial fluid from these hydrogels allows for a rapid improvement of the mechanical strength with adequate cell survival. However, although the UTS of the resulting compressed collagen-rich tissue sheets approach those found in vivo, the break strength, due to the small size of these sheets, does not allow for appropriate handling properties such as suturing. In the present study it was found that both the thickness and the break strength of the compressed sheets could be improved by increasing the (pre-compression) collagen hydrogel volume. It was found here, however, that the previously described anisotropic increase of the collagen density in the hydrogel at the surface through which the interstitial fluid content is removed forms a mass transfer dependent resistance to the outflow of fluid through this surface which indicates that there is a limit to the size and strength of living tissue that can be achieved with this technique. It was found here that the suturability of the compressed sheets could also be enhanced by the hybridisation with a synthetic degradable mesh without compromising cell survival or the speed of construction. Fibroblast seeded hybrid constructs featuring a near confluent epithelial monolayer and with a stratified epithelium, created within 5 hours and 2 weeks respectively, were tested in a lapine model of an acute full thickness skin defect to test for their safety and efficacy in wound healing. Only constructs with a stratified epidermis showed a significant increase in wound closure and neo-vascularisation of the wound bed compared to untreated wounds. Comparison of the present findings with currently available living biological dressings for the treatment of chronic wounds suggests the utility and possible cost-effectiveness of this rapid tissue engineering technique.
|Title:||A rapidly fabricated dermal equivalent|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of) > Institute of Orthopaedics and Musculoskeletal Science|
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