P‐II‐01 
Development of allogeneic cultured dermal substitute (CDS)

The authors have developed a CDS by culturing fibroblasts on the two‐layered spongy matrix of hyaluronic acid (HA) and atelo‐collagen (Col). This CDS is designed to promote wound healing by synergistic effect of fibroblasts and matrix. Both HA and Col molecules seem to function biologically in the process of wound healing. HA molecules play a critical role in several cellular functions such as migration and proliferation by promoting adhesion and disadhesion between the cell and the tissue substrate. Besides providing structural support and strength to the new tissue, Col molecules have a profound effect on the cells within and on its matrix. Col and Col‐derived peptides act as chemoattractants for fibroblasts in vitro and may have a similar activity in vivo. Fibroblasts seeded on the Col surface of two‐layered spongy matrix were found to attach, proliferate, and release vascular endothelial growth factor (VEGF) as well as fibronectin. The cryopreserved CDS was found to keep the original potency to release VEGF after thawing followed by re‐culturing. Multi‐center's clinical research using allogeneic CDS has been proceeded as a national millennium project for regenerative medicine. These products are able to be stored in a freezer and transported to other hospitals in a frozen state. The clinical evaluation involving 180 cases has been already conducted using allogeneic cryopreserved CDS at 30 hospitals across Japan since April 2001. The results obtained in our clinical study suggest that this type of allogeneic CDS is able to provide an effective therapy for patients with severe full‐thickness skin defects. These excellent clinical evaluations seem to be closely related to the results obtained in this fundamental study, especially related to the potency of cryopreserved allogeneic CDS to release VEGF and fibronectin.