Negron Leonardo, Lun Stan, May Barnaby C H
Mesynthes Limited, Lower Hutt 5040, New Zealand.
Int Wound J. 2014 Aug;11(4):392-7. doi: 10.1111/j.1742-481X.2012.01106.x. Epub 2012 Nov 1.
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.
蛋白酶在伤口愈合和组织再生过程中细胞外基质(ECM)成分的有序重塑中起着关键作用。然而,由于基质金属蛋白酶(MMPs)和中性粒细胞弹性蛋白酶(NE)的过度表达和高浓度,慢性伤口中通常有序的蛋白水解受到损害。羊前胃基质(OFM)是一种为组织再生应用(包括慢性伤口治疗)开发的基于脱细胞细胞外基质的生物材料,是ECM蛋白和蛋白聚糖的异质混合物,保留了组织ECM的天然结构和功能特征。鉴于OFM中存在多种分子种类,我们假设OFM可能含有抑制MMP和NE活性的成分或片段。OFM提取物被证明是一系列组织MMPs(IC50 = 23±5至115±14μg/ml)和NE(IC50 = 157±μg/ml)的有效抑制剂,并且比从已知蛋白酶调节伤口敷料制备的提取物更有效。OFM对不同类别的MMPs(即胶原酶、明胶酶和基质溶解素)的广谱活性可能通过更有效地解决慢性伤口中出现的蛋白酶失衡而提供临床优势。