Epidermal-dermal interactions regulate gelatinase activity in Apligraf, a tissue-engineered human skin equivalent

Area of Science:

• Dermatology
• Tissue Engineering
• Wound Healing Research

Background:

• Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are crucial for skin development, repair, and maintenance.
• MMP-2 and MMP-9 (gelatinases) play a role in regulating keratinocyte migration.

Purpose of the Study:

• To investigate if Apligraf, a tissue-engineered human skin equivalent (HSE), produces gelatinases and TIMPs.
• To determine if epidermal-dermal interactions within Apligraf regulate MMP activity.

Main Methods:

• Immunohistochemistry was used to analyze the tissue distribution of MMP-2, MMP-9, TIMP-1, TIMP-2, and fibronectin.
• Fluorimetric assays and gelatin zymography quantified secreted MMP activity and monitored gelatinases in tissue culture supernatants.

Main Results:

• Apligraf expressed MMP-2 and MMP-9, with gelatinases predominantly produced in the epidermis.
• TIMP-1 and TIMP-2 were detected in the dermal component, while fibronectin was exclusively dermal.
• Separating the epidermis and dermis revealed enhanced MMP-9 production by the epidermis and MMP-2 secretion by the dermis, with higher MMP activity in the separated epidermis.

Conclusions:

• Epidermal-dermal interactions in Apligraf suppress epidermal gelatinase activity.
• The coexpression of TIMPs and fibronectin in the Apligraf dermis indicates potential to manage matrix imbalance in chronic wounds.
• Apligraf may support wound re-epithelialization by counteracting matrix degradation.