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Small (Weinheim An Der Bergstrasse,... Nov 2020Osteoarthritis, a lubrication dysfunction related disorder in joint, is characterized by articular cartilage degradation and joint capsule inflammation. Enhancing joint...
Osteoarthritis, a lubrication dysfunction related disorder in joint, is characterized by articular cartilage degradation and joint capsule inflammation. Enhancing joint lubrication, combined with anti-inflammatory therapy, is considered as an effective strategy for osteoarthritis treatment. Herein, based on the ball-bearing-inspired superlubricity and the mussel-inspired adhesion, a superlubricated microsphere, i.e., poly (dopamine methacrylamide-to-sulfobetaine methacrylate)-grafted microfluidic gelatin methacrylate sphere (MGS@DMA-SBMA), is developed by fabricating a monodisperse, size-uniform microsphere using the microfluidic technology, and then a spontaneously modified microsphere with DMA-SBMA copolymer by a one-step biomimetic grafting approach. The microspheres are endowed with enhanced lubrication due to the tenacious hydration layer formed around the charged headgroups (-N (CH ) - and -SO ) of the grafted poly sulfobetaine methacrylate (pSBMA), and simultaneously are capable of efficient drug loading and release capability due to their porous structure. Importantly, the grafting of pSBMA enables the microspheres with preferable properties (i.e., enhanced lubrication, reduced degradation, and sustained drug release) that are highly desirable for intraarticular treatment of osteoarthritis. In addition, when loaded with diclofenac sodium, the superlubricated microspheres with excellent biocompatibility can inhibit the tumor necrosis factor α (TNF-α)-induced chondrocyte degradation in vitro, and further exert a therapeutic effect toward osteoarthritis in vivo.
Topics: Humans; Lubricants; Methacrylates; Microspheres; Osteoarthritis; Polymers
PubMed: 32940012
DOI: 10.1002/smll.202004519 -
Acta Biomaterialia Mar 2022Osteochondral lesion potentially causes a variety of joint degenerative diseases if it cannot be treated effectively and timely. Microfracture as the conservative...
Osteochondral lesion potentially causes a variety of joint degenerative diseases if it cannot be treated effectively and timely. Microfracture as the conservative surgical choice achieves limited results for the larger defect whereas cartilage patches trigger integrated instability and cartilage fibrosis. To tackle aforementioned issues, here we explore to fabricate an integrated osteochondral scaffold for synergetic regeneration of cartilage and subchondral bone in one system. On the macro level, we fabricated three integrated scaffolds with distinct channel patterns of Non-channel, Consecutive-channel and Inconsecutive-channel via Selective Laser Sintering (SLS). On the micro level, both cartilage zone and subchondral bone zone of integrated scaffold were made of small polycaprolactone (PCL) microspheres and large PCL microspheres, respectively. Our findings showed that Inconsecutive-channel scaffolds possessed integrated hierarchical structure, adaptable compression strength, gradient interconnected porosity. Cartilage zone presented a dense phase for the inhibition of vessel invasion while subchondral bone zone generated a porous phase for the ingrowth of bone and vessel. Both cartilage regeneration and subchondral bone remodeling in the group of Inconsecutive-channel scaffolds have been demonstrated by histological evaluation and immunofluorescence staining in vivo. Consequently, our current work not only achieves an effective and regenerative microsphere scaffold for osteochondral reconstruction, but also provides a feasible methodology to recover injured joint through integrated design with diverse hierarchy. STATEMENT OF SIGNIFICANCE: Recovery of osteochondral lesion highly depends on hierarchical architecture and tunable vascularization in distinct zones. We therefore design a special integrated osteochondral scaffold with inconsecutive channel structure and vascularized modulation. The channel pattern impacts on mechanical strength and the infiltration of bone marrow, and eventually triggers synergetic repair of osteochondral defect. The cartilage zone of integrated scaffolds consisted of small PCL microspheres forms a dense phase for physical restriction of vascularized infiltration whereas the subchondral bone zone made of large PCL microspheres generates porous trabecula-like structure for promoting vascularization. Consequently, the current work indicates both mechanical adaptation and regional vascularized modulation play a pivotal role on osteochondral repair.
Topics: Biomimetics; Microspheres; Polyesters; Tissue Engineering; Tissue Scaffolds
PubMed: 35041901
DOI: 10.1016/j.actbio.2022.01.021 -
Journal of Chromatography. A Sep 2022Fluorous affinity chromatography has received growing attention in separation and purification of fluoro compounds, but the wettability of the fluorinated stationary...
Fluorous affinity chromatography has received growing attention in separation and purification of fluoro compounds, but the wettability of the fluorinated stationary phases is seldom noticed. Here, we construct a series of micro-sized fluorine-containing microspheres by solvothermal precipitation polymerization. The fluorinated microspheres could be obtained with narrow size distribution at even high monomer loading of 15 wt%. Through alternating fluoro monomer, both the particle size and the wettability of the microsphere array could be tuned. Among them, the poly(divinylbenzene -dodecafluoroheptyl methacrylate), P(DVB-DFHMA), microsphere (6.1 μm) arrays displays superhydrophobicity with 153.2° water contact angle. The P(DVB-DFHMA) fluorinated microspheres (7.58% fluorine content) can be packed into steel-less columns as stationary phase for high-performance liquid chromatography. The retention mechanism of the fluorinated column is proven to be the specific fluorine-fluorine interaction. Compared to the commercial C18 silica column, the fluorinated column can completely separate fluorine-containing compounds under high water content mobile phase, including small fluoro molecules and fluoro macromolecules, at much lower back pressure by fluorous affinity.
Topics: Chromatography, Affinity; Chromatography, High Pressure Liquid; Fluorine; Hydrophobic and Hydrophilic Interactions; Methacrylates; Microspheres; Silicon Dioxide; Water
PubMed: 36001909
DOI: 10.1016/j.chroma.2022.463428 -
Environmental Research Jul 2023A novel Mg-loaded chitosan carbonized microsphere (MCCM) was prepared for simultaneous adsorption of ammonium and phosphate in this study, through the investigation of...
A novel Mg-loaded chitosan carbonized microsphere (MCCM) was prepared for simultaneous adsorption of ammonium and phosphate in this study, through the investigation of preparation procedures, addition ratio, and preparation temperature. Pollutants removals by MCCM were more acceptable with 64.71% for ammonium and 99.26% for phosphorus, compared with chitosan carbonized microspheres (CCM), Mg-loaded chitosan hydrogel beads (MCH) and MgCl·6HO. Addition ratio of 0.6:1 (m: m) and preparation temperature of 400 °C in MCCM preparation were responsible for pollutant removal and yield. The effect analysis of MCCM dosage, solution pH, pollutant concentration, adsorption mode and coexisting ions on the removal for both ammonium and phosphate indicated that pollutants removals were increased with increasing MCCM dosages, and achieved the peak at pH 8.5, but presented to be stable with Na, K, Ca, Cl, NO, CO and SO, except for Fe.Adsorption mechanisms discussion implied that simultaneous ammonium and phosphate removal with MCCM was attributed to struvite precipitation, ion exchange, hydrogen bonding, electrostatic attraction and Mg-P complexation, suggesting that MCCM presents a new way for simultaneous concentrated ammonium and phosphate removal in wastewater treatment.
Topics: Phosphates; Ammonium Compounds; Chitosan; Microspheres; Adsorption; Environmental Pollutants; Water Pollutants, Chemical; Hydrogen-Ion Concentration; Kinetics
PubMed: 37024031
DOI: 10.1016/j.envres.2023.115850 -
Drug Delivery Dec 2021Poly(lactic-co-glycolic acid) (PLGA) has garnered increasing attention as a candidate drug delivery polymer owing to its favorable properties, including its excellent... (Review)
Review
Poly(lactic-co-glycolic acid) (PLGA) has garnered increasing attention as a candidate drug delivery polymer owing to its favorable properties, including its excellent biocompatibility, biodegradability, non-toxicity, non-immunogenicity, and mechanical strength. PLAG are specifically used as microspheres for the sustained/controlled and targeted delivery of hydrophilic or hydrophobic drugs, as well as biological therapeutic macromolecules, including peptide and protein drugs. PLGAs with different molecular weights, lactic acid (LA)/glycolic acid (GA) ratios, and end groups exhibit unique release characteristics, which is beneficial for obtaining diverse therapeutic effects. This review aims to analyze the composition of PLGA microspheres, and understand the manufacturing process involved in their production, from a quality by design perspective. Additionally, the key factors affecting PLGA microsphere development are explored as well as the principles involved in the synthesis and degradation of PLGA and its interaction with active drugs. Further, the effects elicited by microcosmic conditions on PLGA macroscopic properties, are analyzed. These conditions include variations in the organic phase (organic solvent, PLGA, and drug concentration), continuous phase (emulsifying ability), emulsifying stage (organic phase and continuous phase interaction, homogenization parameters), and solidification process (relationship between solvent volatilization rate and curing conditions). The challenges in achieving consistency between batches during manufacturing are addressed, and continuous production is discussed as a potential solution. Finally, potential critical quality attributes are introduced, which may facilitate the optimization of process parameters.
Topics: Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Compounding; Drug Liberation; Microspheres; Molecular Weight; Polylactic Acid-Polyglycolic Acid Copolymer
PubMed: 34180769
DOI: 10.1080/10717544.2021.1943056 -
Optics Letters Sep 2022We propose a novel, to the best of our knowledge, sensor for nanovibration detection based on a microsphere. The sensor consists of a stretched single-mode fiber and a 2...
We propose a novel, to the best of our knowledge, sensor for nanovibration detection based on a microsphere. The sensor consists of a stretched single-mode fiber and a 2 µm microsphere. The light from the optical fiber passes through the microsphere, forming a photonic nanojet (PNJ) phenomenon at the front of the microsphere. The evanescent field in the PNJ enhances the light reflected from the measured object to the single-mode fiber-microsphere probe (SMFMP). Results showed that the system can detect arbitrary nanovibration waveforms in real time with an SMFMP detection resolution of 1 nm. The voltage signal received and the vibration amplitude showed a good linear relationship within the range of 0-100 nm, with a sensitivity of 0.7 mV/nm and a linearity of more than 99%. The sensor is expected to have potential applications in the field of cell nanovibration detection.
Topics: Microspheres; Optical Fibers; Optics and Photonics; Photons
PubMed: 36048704
DOI: 10.1364/OL.464848 -
Environmental Health Perspectives Apr 2024Global plastic use has consistently increased over the past century with several different types of plastics now being produced. Much of these plastics end up in oceans...
BACKGROUND
Global plastic use has consistently increased over the past century with several different types of plastics now being produced. Much of these plastics end up in oceans or landfills leading to a substantial accumulation of plastics in the environment. Plastic debris slowly degrades into microplastics (MPs) that can ultimately be inhaled or ingested by both animals and humans. A growing body of evidence indicates that MPs can cross the gut barrier and enter into the lymphatic and systemic circulation leading to accumulation in tissues such as the lungs, liver, kidney, and brain. The impacts of mixed MPs exposure on tissue function through metabolism remains largely unexplored.
OBJECTIVES
This study aims to investigate the impacts of polymer microspheres on tissue metabolism in mice by assessing the microspheres ability to translocate across the gut barrier and enter into systemic circulation. Specifically, we wanted to examine microsphere accumulation in different organ systems, identify concentration-dependent metabolic changes, and evaluate the effects of mixed microsphere exposures on health outcomes.
METHODS
To investigate the impact of ingested microspheres on target metabolic pathways, mice were exposed to either polystyrene () microspheres or a mixture of polymer microspheres consisting of polystyrene (), polyethylene (), and the biodegradability and biocompatible plastic, poly-(lactic-co-glycolic acid) (). Exposures were performed twice a week for 4 weeks at a concentration of either 0, 2, or via oral gastric gavage. Tissues were collected to examine microsphere ingress and changes in metabolites.
RESULTS
In mice that ingested microspheres, we detected polystyrene microspheres in distant tissues including the brain, liver, and kidney. Additionally, we report on the metabolic differences that occurred in the colon, liver, and brain, which showed differential responses that were dependent on concentration and type of microsphere exposure.
DISCUSSION
This study uses a mouse model to provide critical insight into the potential health implications of the pervasive issue of plastic pollution. These findings demonstrate that orally consumed polystyrene or mixed polymer microspheres can accumulate in tissues such as the brain, liver, and kidney. Furthermore, this study highlights concentration-dependent and polymer type-specific metabolic changes in the colon, liver, and brain after plastic microsphere exposure. These results underline the mobility within and between biological tissues of MPs after exposure and emphasize the importance of understanding their metabolic impact. https://doi.org/10.1289/EHP13435.
Topics: Humans; Animals; Mice; Polystyrenes; Microspheres; Plastics; Tissue Distribution; Microplastics; Water Pollutants, Chemical
PubMed: 38598326
DOI: 10.1289/EHP13435 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Nov 2017To review the research progress of growth factor sustained-release microspheres in fat transplantation. (Review)
Review
OBJECTIVE
To review the research progress of growth factor sustained-release microspheres in fat transplantation.
METHODS
The recently published 1iterature at home and abroad related the growth factor sustained-release microspheres in fat transplantation was reviewed and analyzed.
RESULTS
The sustained-release microsphere carrier materials include natural polymer materials and synthetic polymer materials.The sustained-release complexes of different microsphere materials with different growth factors can promote the vascularization of transplanted fat in a timely manner, improve the survival rate of grafts, and reduce the incidence of complications such as liquefaction, calcification, and necrosis.
CONCLUSION
The growth factor sustained-release microspheres have the characteristics of persistence and controllability, which is a research hotspot in the field of fat transplantation and has broad application prospects.
Topics: Adipose Tissue; Delayed-Action Preparations; Intercellular Signaling Peptides and Proteins; Microspheres; Polymers
PubMed: 29798599
DOI: 10.7507/1002-1892.201703125 -
Journal of Controlled Release :... Dec 2021Novel formulations of donepezil (DNP)-loaded microspheres based on a bio-degradable polymer of poly(lactic-co-glycolic acid) (PLGA) with a one-month duration of effect...
Novel formulations of donepezil (DNP)-loaded microspheres based on a bio-degradable polymer of poly(lactic-co-glycolic acid) (PLGA) with a one-month duration of effect were developed, aimed at reducing dosing frequency and adverse effects and improving patient adherence. The spherical and monodispersed DNP-loaded microspheres were precisely fabricated by the Inventage Lab Precision Particle Fabrication method (IVL-PPFM®) based on micro-electromechanical systems (MEMS) and microfluidic technology. The types of polymers and end-groups, the drug/polymer ratio (DPR), and the routes of administration for DNP were studied to ensure an effective concentration and desired duration. Laser-light particle size analysis and scanning electron microscopy were used to characterization. Also, non-clinical animal models of beagle dogs are used to optimize DNP formulations and evaluate their pharmacokinetic properties. The PK results showed that the DPR was a critical factor in determining the exposure level and duration of DNR release. Furthermore, the lactide ratio, which varied depending upon the type of polymer, determined the hydrophobic interaction and was also an important factor affecting the desired DNP release. Since DNP shows a large inter-species variation between dogs and humans, PK modeling and simulation of the reference drug (i.e., Aricept®) and DNP-loaded microspheres were used for formulation development to overcome and interpret these variations. In addition, the developed PK model was extrapolated to humans using the estimated PK parameter and published clinical pharmacology data for DNP. The predicted PK profile of the DNP-loaded microsphere in humans showed that the formulation with PLGA 7525A and the DPR of 1/9 could maintain drug concentration for a month and could control initial burst release. The data obtained from the study could be used as scientific evidence for decision-making in future formulation development.
Topics: Animals; Dogs; Donepezil; Lactic Acid; Microscopy, Electron, Scanning; Microspheres; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer
PubMed: 34715262
DOI: 10.1016/j.jconrel.2021.10.022 -
Journal of Controlled Release :... Dec 2022The pH inside the aqueous pores of poly(lactic-co-glycolic acid) (PLGA) microspheres, often termed microclimate pH (μpH), has been widely evaluated in vitro and shown...
The pH inside the aqueous pores of poly(lactic-co-glycolic acid) (PLGA) microspheres, often termed microclimate pH (μpH), has been widely evaluated in vitro and shown to commonly be deleterious to pH-labile encapsulated drug molecules. However, whether the in vitro μpH is representative of the actual in vivo values has long been remained a largely unresolved issue. Herein we quantitatively mapped, for the first time, the in vivo μpH distribution kinetics inside degrading PLGA microspheres by combining two previously validated techniques, a cage implant system and confocal laser scanning microscopy. PLGA (50/50, Mw = 24-38 kDa, acid-end capped and ester-capped) microsphere formulations with and without encapsulating exenatide, a pH-labile peptide that is known to be unstable when pH > 4.5, were administered to rats subcutaneously via cage implants for up to 6 weeks. The results were compared with two different in vitro conditions. Strikingly, the in vivo μpH developed similarly to the low microsphere concentration in vitro condition with 1-μm nylon bags but very different from conventional high microsphere concentration sample-and-separate conditions. Improved maintenance of stable external pH in the release media for the former condition may have been one important factor. Stability of exenatide remaining inside microspheres was evaluated by mass spectrometry and found that it was steadily degraded primarily via pH-dependent acylation with a trend that slightly paralleled the changes in μpH. This methodology may be useful to elucidate pH-triggered instability of PLGA encapsulated drugs in vivo and for improving in vivo-predictive in vitro conditions for assessing general PLGA microsphere performance.
Topics: Animals; Rats; Exenatide; Hydrogen-Ion Concentration; Lactic Acid; Microspheres; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer
PubMed: 36030989
DOI: 10.1016/j.jconrel.2022.08.043