Reduced contraction of skin equivalent engineered using cell sheets cultured in 3D matrices

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The cell sheets that have been tissue-engineered in the past few years have had poor mechanical properties. Because of the fragility of cell sheets, external supports such as stainless steel rings and non-degradable polymeric membranes have to be used. In this experiment, they used two different types of 3D matrices with cultured fibroblast sheets to form a possible tissue engineered skin replacement that have the mechanical properties more similar to native skin. These would maintain their regenerative capacity while also showing reduced wound contraction when transplanted in vivo. The two 3D matrices they used were a weft-knitted poly (lacted-co-glycolic acid) mesh (PLGA), which has mechanical properties similar to native skin while also supporting dermal fibroblast attachment and proliferation, and a collagen sponge crosslinked with hyaluronic acid (CHA), which has greater resistance to enzymatic degredation along with reduced swelling.

The drawback in using cell sheets is that the poor mechanical properties results in difficulty in handling the sheets along with extensive contraction . The results of the expirement showed that the weft-knitted PLGA mesh was better than the CHA sponge because it provided high flexibility that was mechanically stable as a graft. The PLGA-cell sheet showed contraction comparable to autografts. These PLGA-cell sheets contracted less compared to using PLGA alone, showing a synergistic effect between the PLGA mesh and the cell sheets in preventing contraction in a wound, which would lead to less scar formation. The CHA matrix didn’t show great results in vivo because of its rigidity, which prevented it from adapting to the movement of the animals that resulted in wound healing under the matrices instead of over the matricies.

I chose this paper because our project is on TE skin. Although we won’t have a chance to experiment much using different types of 3D matrices like in this experiment, I thought it was a good reminder for us to think of design principles for our devices that can be used clinically in the real world. Even if we were to eventually create a skin sheet that showed nearly all the biological and chemical properties of natural skin tissue, putting the device into a patient for them to actually use is another huge consideration. If the device can’t be placed in a practical and viable way, then it is pretty much useless. It was also interesting to see the thought process of the entire experiment because they used a wide range of laboratory techniques, most of which we learned throughout the semester (cell culture, mechanical properties, microscopy, antibodies, etc.).