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Gout flare-up, commonly resulting from monosodium urate monohydrate (MSUM) crystallization, has led to painful inflammatory arthritis among hundreds of millions of people. Herein, a kind of hydrogel nanoparticles (HNPs) with specific properties was developed, aimed at providing a promising pathway for MSUM crystallization control. The experimental and molecular dynamics simulation results synchronously indicate that the fabricated HNPs achieve efficient inhibition of MSUM crystallization governed by the mechanism of "host-guest interaction" even under very low-dose administration. HNPs as the host dispersed in the hyperuricemic model effectively lift the relative heterogeneous nucleation barrier of the MSUM crystal and hinder solute aggregation with strong electronegativity and hydrophobicity. The initial appearance of MSUM crystals was then delayed from 94 to 334 h. HNPs as the guest on the surface of the formed crystal can decelerate the growth rate by anchoring ions and occupying the active sites on the surface, and the terminal yield of the MSUM crystal declined to less than 1% of the control group. The good biocompatibility of HNPs (cell viability > 94%) renders it possible for future clinical applications. This study can guide the rational design of inhibitory nanomaterials and the development of their application in the control of relevant pathological crystallization.

A bionic platform based on hydrogel composited membrane (HCM, simulating in vivo heterogeneous interface) is constructed to improve the monosodium urate monohydrate (MSUM) crystallization environment in vitro and simulate the mass transfer process of coffee's metabolites in the joint system, which can reveal the potential mechanism of coffee intake to reduce the risk of gout. [Display omitted] Herein, a facile bionic research platform with fabricated hydrogel composite membrane (HCM) is constructed to uncover the effects of the main components of coffee's metabolites on MSUM crystallization. Tailored and biosafety polyethylene glycol diacrylate/ N -isopropyl acrylamide (PEGDA/NIPAM) HCM allows the proper mass transfer of coffee's metabolites and can well simulate the process of coffee's metabolites acting in the joint system. With the validations of this platform, it is shown that chlorogenic acid (CGA) can hinder the MSUM crystals formation from 45 h (control group) to 122 h (2 mM CGA), which is the most likely reason that reduces the risk of gout after long-term coffee consumption. Molecular dynamics simulation further indicates that the high interaction energy (E int) between CGA and MSUM crystal surface and the high electronegativity of CGA both contribute to the restraint of MSUM crystal formation. In conclusion, the fabricated HCM, as the core functional materials of the research platform, presents the understanding of the interaction between coffee consumption and gout control. [ABSTRACT FROM AUTHOR]

Fabricated hydrogel composited membrane (HCM) is developed to reproduce the crystallization environment of monosodium urate monohydrate (MSUM) and then is equipped on a facile and versatile dynamic bionic platform to reveal the pathogenesis and control mechanism of gout after alcohol consumption. Especially, PEGDA/AA HCM can achieve the effective delay of MSUM nucleation and inhibition the crystals deposition (from 100% to 7.5%). [Display omitted] • Facile and versatile HCM based bionic platform was developed for gout control research. • Potential trigger mechanism of gout attack after alcohol intake was revealed. • PEGDA/AA HCM with abundant carboxylic acid groups effectively restrained MSUM crystallization. Gout is the most common of inflammatory arthropathy caused by the crystallization and accumulation of monosodium urate monohydrate (MSUM) in joints. Herein, fabricated hydrogel composited membrane (HCM) is developed to simulate the mass transfer in joints. A facile and versatile HCM based dynamic platform is established to investigate the "triggers" mechanism of gout under alcohol and its metabolites (acetaldehyde (AH) and acetic acid (HAc) intake condition. The distinct role of EtOH on enhanced gout onset was demonstrated, which attributes to the low interaction energy (E int) between EtOH and the main crystal surface. While, HAc and carboxyl groups exhibit potentially restrain the MSUM crystallization. This conclusion is furtherly confirmed by the different restraint performance of two kinds of fabricated HCM. PEGDA/AA (polyethylene glycol diacrylate/acrylic acid) with abundant carboxyl groups can delay the appearance time of MSUM crystals from 20 h to 82 h and reduce the crystal yield to 7.5% of the one via PEGDA/NIPAM (N-isopropylacrylamide). The excellent electronegativity of PEGDA/AA renders the adsorption of sodium ion on the HCM interface, which furtherly increases the nucleation energy barrier of MSUM crystal. The functional HCM based platform can guide the relevant biomedical research and rational drug design for gout prevention. [ABSTRACT FROM AUTHOR]

• Two flow regimes were observed in membrane assisted reactive crystallization (MARC). • Reversible transitions between liquid layer and droplet can be achieved on membrane surface. • Controllable mixing and ions diffusion conditions were achieved via MARC. • Crystals with narrow nano/micro size distribution were obtained via MARC. Herein, membrane-assisted reactive crystallization (MARC) with effective interfacial flow regimes was proposed to achieve the effective mass transfer control during reactive crystallization. Three tube-shell side solution systems (EtOH-H 2 O, Butanol-H 2 O and H 2 O-H 2 O) were chosen to form different flow regimes on the membrane surface, including the microscale liquid layer and the uniform droplets. The fundamental mechanisms of 'rising and falling tide' phenomenon, and flexible layer thickness control were uncovered. A force analysis model was established to illustrate the transition behavior of the droplet and liquid layer on the membrane surface. Molecular simulations additionally demonstrated that MARC implemented various ion diffusion conditions in different solution systems. Compared to the conventional reactive crystallization, MARC with multiple flow regimes can achieve effective control of CaCO 3 crystal size ranging from 700 nm to 3 μm and obtain uniform size distribution (coefficient of variation less than 15.1 %), which shed light on the advanced material manufacture with reactive crystallization process. [ABSTRACT FROM AUTHOR]