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Published on: August 22, 2016
Promotion of acellular dermal matrix resolution in vitro by matrix metalloproteinase-2
Jonathan P Lindman1, Melissa Talbert, Wenyue Zhang
1Division of Otolaryngology, Department of Surgery, and Department of Biostatistics, University of Alabama at Birmingham, 35294-0012, USA.
Objective:
To determine whether acellular human dermis is degraded by matrix metalloproteinases (MMPs), a large class of matrix-degrading enzymes.
Methods:
The degradation of acellular human dermis specimens was evaluated in vitro. Wild-type murine fibroblasts with a broad-spectrum MMP inhibitor, GM6001, and MMP-2-deficient fibroblasts were placed on the basement membrane and dermal surfaces of acellular human dermis. Matrix degradation and fibroblast infiltration into the matrix were assessed after a 20-day incubation period.
Results:
The basement membrane thickness of the specimens cultured with wild-type fibroblasts was significantly less than that of specimens cultured with GM6001 (P<.001), and the infiltration of fibroblasts into the dermal surface was limited by the addition of GM6001 (P=.002). To determine whether MMP-2 was involved in this in vitro phenotype, MMP-2-deficient fibroblasts were assessed in comparison with wild-type fibroblasts. Wild-type fibroblasts degraded the basement membrane surface (P<.001) and infiltrated the dermal surface (P = .003) more efficiently than did MMP-2-deficient fibroblasts.
Conclusions:
The results from our in vitro experiments suggest that MMPs and specifically MMP-2 may play an important role in the resorption of acellular human dermis. Addition of MMP inhibitors to implanted dermal matrices may slow fibroblast infiltration and improve their longevity in vivo.
Insights
Matrix metalloproteinases (MMPs), particularly MMP-2, degrade acellular human dermis. Inhibiting MMPs may enhance the longevity of implanted dermal matrices by slowing fibroblast infiltration.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Dermatology
Background:
- Acellular human dermis is a common biomaterial used in tissue regeneration.
- Matrix metalloproteinases (MMPs) are enzymes known to degrade extracellular matrix components.
Purpose of the Study:
- To investigate the degradation of acellular human dermis by MMPs.
- To determine the role of MMP-2 in this degradation process.
Main Methods:
- In vitro evaluation of acellular human dermis degradation using wild-type and MMP-2-deficient fibroblasts.
- Assessment of matrix degradation and fibroblast infiltration with and without a broad-spectrum MMP inhibitor (GM6001).
Main Results:
- Wild-type fibroblasts significantly reduced basement membrane thickness compared to controls with GM6001.
- Fibroblast infiltration was significantly reduced by GM6001.
- Wild-type fibroblasts degraded the basement membrane and infiltrated the dermis more effectively than MMP-2-deficient fibroblasts.
Conclusions:
- MMPs, especially MMP-2, appear to play a key role in the resorption of acellular human dermis.
- Inhibiting MMPs could potentially improve the in vivo performance of implanted dermal matrices by modulating fibroblast activity.
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