Fibroblast sheets enable epithelialization of sounds that do not support keratinocyte migration

Area of Science:

• Wound healing research
• Tissue engineering
• Dermatology

Background:

• Keratinocyte migration is crucial for wound epithelialization.
• Chronic wounds, burns, and ulcers often exhibit impaired wound bed matrices, hindering healing.
• Improving the wound bed environment can reduce patient hospitalization times.

Purpose of the Study:

• To investigate the role of cultured human fibroblasts in promoting keratinocyte migration and wound epithelialization.
• To determine if a fibroblast-derived matrix can facilitate healing in wounds with poor epithelialization capacity.

Main Methods:

• Wound epithelialization was studied in athymic mice with and without fibroblast sheets.
• Keratinocyte physiology on fibroblast sheets was analyzed using histology, immunofluorescence, and electron microscopy.
• In vitro studies examined keratinocyte outgrowth on fibroblast sheets at the air/liquid interface.

Main Results:

• Keratinocytes failed to migrate on untreated wounds in athymic mice.
• Fibroblast-seeded polyglactin mesh significantly enhanced keratinocyte outgrowth on wounds.
• Human keratinocytes exhibited robust outgrowth on fibroblast sheets in vitro.
• Fibroblast-derived extracellular matrix, rich in Collagen IV, promoted keratinocyte migration.

Conclusions:

• A conducive substrate, such as a fibroblast-derived matrix, can enable epithelialization in wounds that otherwise fail to support keratinocyte migration.
• The extracellular matrix and matrix-bound growth factors secreted by fibroblasts are key to promoting keratinocyte migration.
• This approach holds promise for treating chronic wounds, burns, and ulcers.