title: Ovine forestomach matrix biomaterial is a broad spectrum inhibitor of matrix metalloproteinases and neutrophil elastase.
abstract: Proteases play a critical role in the ordered remodelling of extracellular matrix (ECM) components during wound healing and tissue regeneration. However, the usually ordered proteolysis is compromised in chronic wounds due to over-expression and high concentrations of matrix metalloproteinase's (MMPs) and neutrophil elastase (NE). Ovine forestomach matrix (OFM) is a decellularised extracellular matrix-based biomaterial developed for tissue regeneration applications, including the treatment of chronic wounds, and is a heterogeneous mixture of ECM proteins and proteoglycans that retains the native structural and functional characteristics of tissue ECM. Given the diverse molecular species present in OFM, we hypothesised that OFM may contain components or fragments that inhibit MMP and NE activity. An extract of OFM was shown to be a potent inhibitor of a range of tissue MMPs (IC50 s = 23 ± 5 to 115 ± 14 µg/ml) and NE (IC50 = 157 ± 37 µg/ml), and was more potent than extracts prepared from a known protease modulating wound dressing. The broad spectrum activity of OFM against different classes of MMPs (i.e. collagenases, gelatinases and stromelysins) may provide a clinical advantage by more effectively addressing the protease imbalance seen in chronic wounds.
authors.affiliation: Mesynthes Limited, Lower Hutt 5040, New Zealand.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Negron
authors.forename: Stan
authors.initials: S
authors.lastname: Lun
authors.forename: Barnaby C H
authors.initials: BC
authors.lastname: May
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D005109:Extracellular Matrix; D019272:Leukocyte Elastase / Q000187:drug effects / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism; D053491:Proteinase Inhibitory Proteins, Secretory / Q000494:pharmacology*; D012038:Regeneration / Q000502:physiology*; D012756:Sheep; D013270:Stomach / Q000166:cytology*; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000628:therapy*
chemical_list: D001672:Biocompatible Materials; D061965:Matrix Metalloproteinase Inhibitors; D053491:Proteinase Inhibitory Proteins, Secretory; D019272:Leukocyte Elastase; D020782:Matrix Metalloproteinases
keywords: Enzyme inhibitor; Inhibition; Matrix metalloproteinase; Neutrophil elastase; Ovine forestomach matrix; Wound healing