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Pressure ulcers

Hard-to-heal wounds

Leg ulcers

Diabetic foot ulcers

Wound dressings

Cell salvage in acute and chronic experimental data and early clinical results

02 February 2019

Review

02 February 2019

Volume 3 · Issue 1

ISSN (print): 0969-0700

ISSN (online): 2052-2916

Abstract

On 9 May 2018, the authors took part in a closed panel discussion on the impact of cell salvage in acute and chronic wounds. The goal was to deliberate the possible use of plurogel micelle matrix (PMM) as a new treatment strategy for wound healing and the authors openly shared their experiences, thoughts, experimental data and early clinical results. The outcome of the panel discussion has been abridged in this paper. The cell membrane consists of a lipid bilayer, which provides a diffusion barrier separating the inside of a cell from its environment. Cell membrane injury can result in acute cellular necrosis when defects are too large and cannot be resealed. There is a potential hazard to the body when these dying cells release endogenous alarm signals referred to as ‘damage (or danger) associated molecular patterns' (DAMPs), which trigger the innate immune system and modulate inflammation. Cell salvage by membrane resealing is a promising target to ensure the survival of the individual cell and prevention of further tissue degeneration by inflammatory processes. Non-ionic surfactants such as poloxamers, poloxamines and PMM have the potential to resuscitate cells by inserting themselves into damaged membranes and stabilising the unstable portions of the lipid bilayers. The amphiphilic properties of these molecules are amenable to insertion into cell wall defects and so can play a crucial, reparative role. This new approach to cell rescue or salvage has gained increasing interest as several clinical conditions have been linked to cell membrane injury via oxidative stress-mediated lipid peroxidation or thermal disruption. The repair of the cell membrane is an important step in salvaging cells from necrosis to prevent further tissue degeneration by inflammatory processes. This is applicable to acute burns and chronic wounds such as diabetic foot ulcers (DFUs), chronic venous leg ulcers (VLUs), and pressure ulcers (PUs). Experimental data shows that PMM is biocompatible and able to insert itself into damaged membranes, salvaging their barrier function and aiding cell survival. Moreover, the six case studies presented in this paper reveal the potential of this treatment strategy.

Injury to the body might macroscopically present as a disruption of tissues, but eventually it is the cells in this tissue that are damaged. With the emergence of molecular medicine, correction or reversal of pathological states at the cellular/molecular level now seems possible.

The concept of cell salvage has primarily been linked to damage like myocardial infarction,^1,2,3,4 dystrophic heart failure,^5,6,7,8 ischaemic stroke,^9–10 traumatic brain injury,^11,12 damage to the nervous system^13,14,15 and renal failure,¹⁶ some of which represent ischaemia-reperfusion-mediated injuries. Under ischaemic conditions, cellular energy stores are rapidly depleted and degradation products quickly amount to toxic concentrations.¹⁶ Subsequent reperfusion, although necessary to restore oxygen and the supply of nutrients, has been associated with pathological inflammatory reactions.¹⁷ For example, following reperfusion of ischaemic myocardium, an increase in protease activity, the release of cytokines and other proinflammatory mediators (like IL-1β, TNF-α, and C5a), and excessive formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been reported.¹⁷ The oxidative stress that results when the production of free radicals exceeds the tissue's antioxidative capacity^1,13 damages major cellular components such as DNA, proteins and lipids, causing cell death.³ There has been a steady increase in interest in cell membrane dysfunction associated with oxidative stress, particularly as traumatic mechanical or electrical injuries could also be linked to cell membrane integrity failure and subsequent cell death.^{10,11,12,13,14,15,18,19,20}

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cell salvage

lipid bilayer

plurogel

plurogel micelle matrix

surfactants

wound healing