Bioreactor Maintained Living Skin Matrix

Abstract

Numerous reconstructive procedures result in wounds that require skin grafting. Often, the amount of tissue available from donor sites is limited. In vivo tissue expanders have been used clinically to generate larger sections of skin, and other methods exist to cover large wounds, but all have significant limitations. We investigated whether these difficulties could be overcome by increasing the surface area of skin in vitro while maintaining tissue viability. Human foreskin was incrementally expanded in a computer-controlled bioreactor system over 6 days to increase its surface dimensions under culture conditions. Morphological, ultrastructural, and mechanical properties of the foreskin were evaluated before and after expansion using histology, scanning electron microscopy, mercury porosimetry, and tensile testing. The surface area of the tissue was 110.7% +/- 12.2% greater, with maintenance of cell viability and proliferative potential. Histomorphological and ultrastructural analyses showed that dermal structural integrity was preserved. The pore diameter of the expanded skin was 64.49% +/- 32.8% greater. The mechanical properties were not adversely affected. These findings show that expansion of living skin matrices can be achieved using a computer-controlled bioreactor system. This technique provides an opportunity to generate large amounts of skin for reconstructive procedures.

In vitro skin expansion: Wound healing assessment

“…The initial study of in vitro skin expansion also showed high levels of cellular proliferation and concluded that there was no thickness change over the expansion process. Their expansion process was strain based (4% length increase per hour for five consecutive hours, once per day for five days) and resulted in considerably more expansion over a shorter period: > 100% expansion in five days.…”

“…Thickness did not change significantly, suggesting that the tissue volume increase was attributed to growth. Histology demonstrated no change in morphology or mitotic activity after expansion . In another study, full‐thickness human grafts have been expanded in vitro and transplanted back to the donor body to correct cicatricial scar contracture from burns and traumas.…”

Applicability and Safety of in Vitro Skin Expansion Using a Skin Bioreactor: A Clinical Trial

“…The distribution of blood vessels dramatically increased during tissue expansion. In the study by Ladd et al [3] in 2009, the skin maintained its original structure and was not affected by in vitro skin expansion, and the cell viability was conserved. Additionally, an increase in pore size following the expansion was observed, and through this, the diffusion of nutrition could improve and angiogenesis could be induced.…”

Current and Future Perspectives on Skin Tissue Engineering: Key Features of Biomedical Research, Translational Assessment, and Clinical Application

“…Although skin is a highly elastic tissue, it is not under constant or cyclic loads in contrast to other tissues such as bone, muscle, or cartilage. Early work by Atala and co‐workers used bioreactor systems for the expansion of living skin matrices to increase the surface area of skin available for reconstructive purposes, while simultaneously demonstrating that the mechanical properties of native skin were not adversely affected using this method . Following trials showed similar success in patient‐derived skin samples, promising a path for clinical applications .…”