Promotion of acellular dermal matrix resolution in vitro by matrix metalloproteinase-2.
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.
Lindman
Jonathan P
JP
Division of Otolaryngology, Department of Surgery, and Department of Biostatistics, University of Alabama at Birmingham, 35294-0012, USA.
Talbert
Melissa
M
Zhang
Wenyue
W
Powell
Benjamin
B
Accortt
Neil A
NA
Rosenthal
Eben L
EL
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D002465:Cell Movement; D020405:Dermis / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2 / Q000494:pharmacology*; D051379:Mice; D018709:Statistics, Nonparametric; D014945:Wound Healing / Q000187:drug effects
D020778:Matrix Metalloproteinase 2