In an 8-year study of 35 patients treated with cultured epithelial autografts (CEA) grafted to fullthickness burn wounds excised to muscle fascia, overall take rates of CEA averaged 55-60%. Biopsies of successfully engrafted CEA were analyzed by light microscopic, immunohistochemical, morphometric, electron microscopic and ultrastructural immunolabelling techniques in order to study skin regeneration and wound healing in these patients. Controls consisted of both normal site-and age-matched skin and healed meshed split-thickness autograft (MSTA) interstices on the same patient biopsied at comparable postgrafting time points. Key events in the regeneration of skin from CEA can be summarized as follows: At transplantation, CEA are undifferentiated and lack both granular and cornified cell layers. By 6 days postgrafting, CEA differentiate all normal epidermal strata but lack rete ridges. De novo formation of a confluent basal lamina and mature hemidesmosomes is completed by about 3 weeks. Anchoring fibrils are sparse and morphologically immature compared to normal skin until about 6-12 months postgrafting, but their maturation rate is identical to that of MSTA interstice controls. Hyperproliferation of the newly differentiated epidermis as judged by increased numbers of Ki67-positive (i.e., cycling) cells within the basal layer continues for 4-6 months after grafting. Expression of hyperproliferative keratins (cytokeratins 6/16) continues throughout the first postgrafting year and may be seen up to two years after transplantation. The site-specific phenotype of the donor skin from which the cultures are grown is reexpressed by the CEA shortly after transprantation and is maintained long-term. CEA develop rete ridges and a neodermis with normal stromal and vascular organization at about 6-12 months, whereas MSTA interstice controls do not. At 4-5 years, elastin expression is also observed in the CEA neodermis, completing the dermal regeneration process. Normal epidermal differentiation is maintained long-term, and no epidermal atypia, dysplasia or atrophy is observed. The long-term results indicate that CEA regenerate a stable normal epidermis and are capable of inducing dermal regeneration from immature wound bed connective tissue. More recent studies on 10 patients in which CEA were transplanted to engrafted, cryopreserved homograft dermis instead of granulation tissue showed increased take rates of CEA (average 85-90%) and acceleration of rete ridge formation and normalization of keratin programs within the differentiated epidermis on histological examination.
ASJC Scopus subject areas
- Infectious Diseases