Metal-Assisted and Microwave-Accelerated Decrystallization of Pseudo-Tophus in Synthetic Human Joint Models.

In this paper, we tested a hypothesis that the metal-assisted and microwave-accelerated decrystallization (MAMAD) technique, based on the combined use of low-power medical microwave heating (MWH) and gold nanoparticles (Au NPs), can be used to decrystallize laboratory-prepared monosodium urate monohydrate crystal aggregate (pseudo-tophus) placed in three-dimensional (3D) synthetic human joint models. To simulate a potential treatment of chronic tophaceous gout using the MAMAD technique, we used three different 3D synthetic human joint models and assessed the percent mass reduction (PMR, i.e., decrystallization) of pseudo-tophus and microwave-induced synthetic skin patch damage after MAMAD sessions (a MAMAD session = 120 s of MWH in the presence of Au NPs). Our three synthetic joint models are: Model 1: Application of seven MAMAD sessions in a closed synthetic joint with a pseudo-bursa containing a pseudo-tophus submerged in a solution of 20 nm Au NPs followed by dehydration of pseudo-tophus after each MAMAD session to assess PMR. Model 2: Application of seven MAMAD sessions in a closed or open synthetic joint with a pseudo-bursa containing a pseudo-tophus submerged in a solution of Au NPs followed by intermittent dehydration of pseudo-tophus after seven MAMAD sessions to assess PMR. Model 3: Application of 18 MAMAD sessions in a rotated closed synthetic joint (three sides are heated separately) with a pseudo-bursa containing a pseudo-tophus submerged in a solution of Au NPs followed by dehydration after every three MAMAD sessions to assess PMR. After a single MAMAD session, pseudo-tophus exposed to MWH and Au NPs had an average PMR of 8.30% (up to an overall PMR of 15%), and microwave-induced damage to the synthetic skin can be controlled by the use of a sacrificial skin sample and by adjusting the duration and the number of the MAMAD sessions. Computational electromagnetic simulations predict a 10% absorption of electric field by the pseudo-tophus placed in the synthetic joint models, which led us to conclude that a medical microwave source with higher power than 20 W can potentially be used with the MAMAD technique.

Microwave Heating of Crystals with Gold Nanoparticles and Synovial Fluid under Synthetic Skin Patches.

Gout is a disease with elusive treatment options. Reduction of the size of l-alanine crystals as a model crystal for gouty tophi with the use of a monomode solid-state microwave was examined as a possible therapeutic aid. The effect of microwave heating on l-alanine crystals in the presence of gold nanoparticles (Au NPs) in solution and synovial fluid (SF) in a plastic pouch through a synthetic skin patch was investigated. In this regard, three experimental paradigms were employed: Paradigm 1 includes the effect of variable microwave power (5-10 W) and variable heating time (5-60 s) and Au NPs in water (20 nm size, volume of 10 µL) in a plastic pouch (1 × 2 cm2 in size). Paradigm 2 includes the effect of a variable volume of 20 nm Au NPs in a variable volume of SF up to 100 µL in a plastic pouch at a constant microwave power (10 W) for 30 s. Paradigm 3 includes the effect of constant microwave power (10 W) and microwave heating time (30 s), constant volume of Au NPs (100 µL), and variable size of Au NPs (20-200 nm) placed in a plastic pouch through a synthetic skin patch. In these experiments, an average of 60-100% reduction in the size of an l-alanine crystal (initial size = 450 µm) without damage to the synthetic skin or increasing the temperature of the samples beyond the physiological range was reported.

Metal-Assisted and Microwave-Accelerated Decrystallization: An Alternative Approach to Potential Treatment of Crystal Deposition Diseases.

Gout is a painful and prevalent crystal deposition disease caused by the overproduction of Uric Acid (UA) in the body and the atypical deposition in human synovial joints as Monosodium Urate Monohydrate (MSUM). Conventional treatments, such as NSAIDs, cyclooxygenase-2 inhibitors, and systemic glucocorticoids often present harmful side-effects and are short-lived. Long-term therapies including xanthine oxidase inhibitors and the use of uricosuric agents have been developed and aim to lower the UA serum levels in the body. As regards to post-crystals deposition, our research laboratory recently proposed and demonstrated the use of the Metal-Assisted and Microwave-Accelerated Decrystallization (MAMAD) technique for the breakdown of organic and biological crystals on planar surfaces. The MAMAD technique is based on the combined use of microwave heating and Au NPs in solution. The interactions of the Au NPs with microwave's electromagnetic field result in an increase in the kinetic energy of Au NPs, and subsequently, an increase in the collisions with target crystals placed on planar surfaces leading to rapid crystal breakdown. In this regard, our laboratory aims to develop the MAMAD technique as an alternative treatment for crystal deposition diseases, particularly gout, with minimal invasion and side-effects as compared to current treatments. In this review article, we will summarize our previous findings and provide additional data detailing the effectiveness of the MAMAD technique as a rapid and efficient method for the breakdown of gout related crystals and L-alanine crystals (a model crystal).