Mimicking the respiratory burst myeloperoxidase system of polymorphonuclear neutrophil granulocytes to aid the wound healing behaviors of articular cartilage

Abstract

Purpose: Articular cartilage exhibits a limited ability to remove damaged tissue from its surfaces, a step integral for efficient mammalian wound healing that is typically enabled by polymorphonuclear neutrophil granulocytes in other tissue types. This limited ability constrains articular cartilage wound healing behaviors, contributing to lesion progression and the disease burden of osteoarthritis. The respiratory burst myeloperoxidase system of polymorphonuclear neutrophil granulocytes produces low stability protonating agents involved in exothermic tissue homeostasis and repair mechanisms through disproportionation redox reactions. Because these protonating agents facilitate the removal of damaged interstitial matrices through biopolymer disaggregation in order to assist differentiated tissue assembly activities, this study evaluates the capability of alternating current redox magnetohydrodynamic technology to mimic this respiratory burst to aid the wound healing behaviors of articular cartilage by creating a healthy lesion site devoid of damaged tissue. Methods: An alternating current redox magnetohydrodynamic device fashioned as a physiochemical scalpel was deployed in 0.9% sodium chloride solutions at 300 mOsm/L and at 20oC. Figure 1 demonstrates the device producing solution changes that are delivered to tissue surfaces as an engineered irrigant during endoscopic procedures designed to stabilize articular cartilage lesions. To determine if the engineered irrigant resembles the protic solvent generated by azurophilic granules, the resultant irrigant temperature and protonation potential were measured as a function of power input during device activation controlled for 5 second steady-state treatment conditions. Irrigant protonation potential was determined by measuring solution electrochemical potential relative to [H+] as a function of differential proton sequestration in the irrigant during device activation. Results: Alternating current redox magnetohydrodynamics in saline solutions is represented in Figure 2. As depicted in Figure 3, the protonation potential increased with direct correlation to power delivery (p < 0.02; R2 = 0.311) and commensurate with a minimal change in irrigant temperature (∼0-5o C) above the baseline 20o C, reflecting features characteristic of the protic solvent generated by the azurophilic degranulation of polymorphonuclear neutrophil granulocytes during the early phases of wound healing. Conclusions: Because resection precision that eliminates both volumetric and functional over-resection is required before surgical lesion stabilization can be an effective aid to articular cartilage wound healing behaviors, polymorphonuclear neutrophil granulocyte function is a valuable therapeutic design resource. Protonation coupled conformational dynamics is an energy transduction processes that achieves nanometer resection precision through a guest chemical denaturization process below the isoelectric point of exposed damaged interstitial tissue matrices. Because of high proton motilities in water solutions, stoichiometric protonation is a very rapid charge redistribution process that leads to biopolymer disaggregation through molecular cleavage planes accessible due to normal tissue surface barrier losses and degenerate matrix properties characteristic of damage tissue sites. Figure 4 illustrates a representative integrated cell viability stain section image that demonstrates removing the bioburden of damaged tissue without iatrogenic over-resection in a human explant model of osteoarthritis by adapting alternating current redox magnetohydrodynamic technology for tissue rescue surgical procedures.