References
Efficacy of MMP-inhibiting wound dressings in the treatment of hard-to-heal wounds: a systematic review
Abstract
Objective:
Matrix metalloproteinases (MMPs) substantially contribute to the development of chronicity in wounds. Thus, MMP-inhibiting dressings may support healing. A systematic review was performed to determine the existing evidence base for the treatment of hard-to-heal wounds with these dressings.
Methods:
A systematic literature search in databases and clinical trial registers was conducted to identify randomised controlled trials (RCTs) investigating the efficacy of MMP-inhibiting dressings. Studies were analysed regarding their quality and clinical evidence.
Results:
Of 721 hits, 16 relevant studies were assessed. There were 13 studies performed with collagen and three with technology lipido-colloid nano oligosaccharide factor (TLC-NOSF) dressings. Indications included diabetic foot ulcers, venous leg ulcers, pressure ulcers or wounds of mixed origin. Patient-relevant endpoints comprised wound size reduction, complete wound closure, healing time and rate. Considerable differences in the quality and subsequent clinical evidence exist between the studies identified. Substantial evidence for significant improvement in healing was identified only for some dressings.
Conclusion:
Evidence for the superiority of some MMP-inhibiting wound dressings exists regarding wound closure, wound size reduction, healing time and healing rate. More research is required to substantiate the existing evidence for different types of hard-to-heal wounds and to generate evidence for some of the different types of MMP-inhibiting wound dressings.
Hard-to-heal wounds are often defined as wounds with delayed or stagnated healing that fail to heal within eight weeks.1 If these wounds are not treated appropriately, they can last for several months or even years and may become severe.2 Frequently occurring hard-to-heal wounds, including diabetic foot ulcers (DFU), venous leg ulcers (VLU) and pressure ulcers (PU), represent a significant burden on economic health and social care costs as well as the patient's quality of life (QoL).3,4,5 Therefore, accelerating the healing process is of particular importance in order to improve patient QoL and to reduce healthcare costs.
Research, on the course of physiological wound healing and those wounds developing chronicity, uncovered key roles for matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).2,6,7,8,9,10 MMPs are a family of more than 20 structurally related endopeptidases involved in many physiological processes, such as cell signaling, cell migration, angiogenesis and the degradation of extracellular matrix (ECM) proteins.11 Wound healing mainly involves MMP-1, -2, -3, -7, -13 and -26.2,11,12 In physiological wound healing they ensure the breakdown of damaged tissue at the start of the healing process.12 However, in the later stages of wound healing, increased MMP activity is undesirable since it is thought that MMPs inhibit the formation of new tissue. At these stages of wound healing, TIMP play an essential role, as they downregulate MMP activity.9,10 In hard-to-heal wounds, this control appears to be impaired, resulting in an imbalance between MMP and TIMP ratio.13 Consequently, healing is delayed or even stagnated and inflammation is prolonged.12,14 Evidence suggests that elevated MMP-levels correlate with delayed healing in patients with many different types of hard-to-heal wounds including DFU, VLU and PU.15,16,17,18
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