PLA plastic particles disrupt bile acid metabolism leading to hepatic inflammatory injury in male mice.

Microplastics, such as polylactic acid (PLA), are ubiquitous environmental pollutants with unclear implications for health impact. This study aims to elucidate the mechanisms of PLA-induced inflammatory liver injury, focusing on disturbance of bile acid metabolism. The in vitro PLA exposure experiment was conducted using HepG2 cells to assess cell viability, cytokine secretion, and effects on bile acid metabolism. In vivo, male C57BL/6 J mice were exposed to PLA for ten days continuously, liver function and histopathological assessment were evaluated after the mice sacrificed. Molecular analyses including quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting, were applied to evaluate the expression of bile acid metabolizing enzymes and transporters. PLA exposure resulted in decreased cell viability in HepG2 cells, increased inflammation and altered bile acid metabolism. In mice, PLA exposure resulted in decreased body weight and food intake, impaired liver function, increased hepatic inflammation, altered bile acid profiles, and dysregulated expression of bile acid metabolic pathways. PLA exposure disrupts bile acid metabolism through inhibition of the CYP7A1 enzyme and activation of the FGF-JNK/ERK signaling pathway, contributing to liver injury. These findings highlight the potential hepatotoxic effects of environmentally friendly plastics PLA and underscore the need for further research on their biological impact.

AgNPs-Modified Polylactic Acid Microneedles: Preparation and In Vivo/In Vitro Antimicrobial Studies.

OBJECTIVE: To prepare polylactic acid microneedles (PLAMNs) with sustained antibacterial effect to avoid skin infection caused by traditional MNs-based biosensors. METHODS: Silver nanoparticles (AgNPs) were synthesized using an in-situ reduction process with polydopamine (PDA). PLAMNs were fabricated using the hot-melt method. A series of pressure tests and puncture experiments were conducted to confirm the physicochemical properties of PLAMNs. Then AgNPs were modified on the surface of PLAMNs through in-situ reduction of PDA, resulting in the formation of PLAMNs@PDA-AgNPs. The in vitro antibacterial efficacy of PLAMNs@PDA-AgNPs was evaluated using agar diffusion assays and bacterial liquid co-culture approach. Wound healing and simulated long-term application were performed to assess the in vivo antibacterial effectiveness of PLAMNs@PDA-AgNPs. RESULTS: The MNs array comprised 169 tiny needle tips in pyramidal rows. Strength and puncture tests confirmed a 100% puncture success rate for PLAMNs on isolated rat skin and tin foil. SEM analysis revealed the integrity of PLAMNs@PDA-AgNPs with the formation of new surface substances. EDS analysis indicated the presence of silver elements on the surface of PLAMNs@PDA-AgNPs, with a content of 14.44%. Transepidermal water loss (TEWL) testing demonstrated the rapid healing of micro-pores created by PLAMNs@PDA-AgNPs, indicating their safety. Both in vitro and in vivo tests confirmed antibacterial efficacy of PLAMNs@PDA-AgNPs. CONCLUSIONS: In conclusion, the sustained antibacterial activity exhibited by PLAMNs@PDA-AgNPs offers a promising solution for addressing skin infections associated with MN applications, especially when compared to traditional MN-based biosensors. This advancement offers significant potential for the field of MN technology.

Enzymatic degradation of polylactic acid (PLA).

Environmental concerns arising from the increasing use of polluting plastics highlight polylactic acid (PLA) as a promising eco-friendly alternative. PLA is a biodegradable polyester that can be produced through the fermentation of renewable resources. Together with its excellent properties, suitable for a wide range of applications, the use of PLA has increased significantly over the years and is expected to further grow. However, insufficient degradability under natural conditions emphasizes the need for the exploration of biodegradation mechanisms, intending to develop more efficient techniques for waste disposal and recycling or upcycling. Biodegradation occurs through the secretion of depolymerizing enzymes, mainly proteases, lipases, cutinases, and esterases, by various microorganisms. This review focuses on the enzymatic degradation of PLA and presents different enzymes that were isolated and purified from natural PLA-degrading microorganisms, or recombinantly expressed. The review depicts the main characteristics of the enzymes, including recent advances and analytical methods used to evaluate enantiopurity and depolymerizing activity. While complete degradation of solid PLA particles is still difficult to achieve, future research and improvement of enzyme properties may provide an avenue for the development of advanced procedures for PLA degradation and upcycling, utilizing its building blocks for further applications as envisaged by circular economy principles. KEY POINTS: • Enzymes can be promisingly utilized for PLA upcycling. • Natural and recombinant PLA depolymerases and methods for activity evaluation are summarized. • Approaches to improve enzymatic degradation of PLA are discussed.

Microneedle delivery system with rapid dissolution and sustained release of bleomycin for the treatment of hemangiomas.

Hemangioma of infancy is the most common vascular tumor during infancy and childhood. Despite the proven efficacy of propranolol treatment, certain patients still encounter resistance or face recurrence. The need for frequent daily medication also poses challenges to patient adherence. Bleomycin (BLM) has demonstrated effectiveness against vascular anomalies, yet its use is limited by dose-related complications. Addressing this, this study proposes a novel approach for treating hemangiomas using BLM-loaded hyaluronic acid (HA)-based microneedle (MN) patches. BLM is encapsulated during the synthesis of polylactic acid (PLA) microspheres (MPs). The successful preparation of PLA MPs and MN patches is confirmed through scanning electron microscopy (SEM) images. The HA microneedles dissolve rapidly upon skin insertion, releasing BLM@PLA MPs. These MPs gradually degrade within 28 days, providing a sustained release of BLM. Comprehensive safety assessments, including cell viability, hemolysis ratio, and intradermal reactions in rabbits, validate the safety of MN patches. The BLM@PLA-MNs exhibit an effective inhibitory efficiency against hemangioma formation in a murine hemangioma model. Of significant importance, RNA-seq analysis reveals that BLM@PLA-MNs exert their inhibitory effect on hemangiomas by regulating the P53 pathway. In summary, BLM@PLA-MNs emerge as a promising clinical candidate for the effective treatment of hemangiomas.

The effect of Dunaliella salina extracts on the adhesion of Pseudomonas aeruginosa to 3D printed polyethylene terephthalate and polylactic acid.

Polyethylene terephthalate (PET) and polylactic acid (PLA) are among the polymers used in the food industry. In this study, crude extracts of Dunaliella salina were used to treat the surface of 3D printed materials studied, aiming to provide them with an anti-adhesive property against Pseudomonas aeruginosa. The hydrophobicity of treated and untreated surfaces was characterized using the contact angle method. Furthermore, the adhesive behavior of P. aeruginosa toward the substrata surfaces was also studied theoretically and experimentally. The results showed that the untreated PLA was hydrophobic, while the untreated PET was hydrophilic. It was also found that the treated materials became hydrophilic and electron-donating. The total energy of adhesion revealed that P. aeruginosa adhesion was theoretically favorable on untreated materials, while it was unfavorable on treated ones. Moreover, the experimental data proved that the adhesion to untreated substrata was obtained, while there was complete inhibition of adhesion to treated surfaces.

Ecotoxicity of polylactic acid microplastic fragments to Daphnia magna and the effect of ultraviolet weathering.

Biodegradable plastics (BPs) are widely used as alternatives to non-BPs due to their inherent ability to undergo facile degradation. However, the ecotoxicological impact of biodegradable microplastics (MPs) rarely remains scientific documented especially to aquatic ecosystem and organisms compared to conventional microplastics. Therefore, this study aimed to investigate the ecotoxicity of biodegradable polylactic acid (PLA) MPs to Daphnia magna with that of conventional polyethylene (PE) MPs with and without ultraviolet (UV) treatment (4 weeks). The acute toxicity (48 h) of PLA MPs was significantly higher than that of PE MPs, potentially attributable to their elevated bioconcentration resulting from their higher density. UV treatment notably reduced the particle size of PLA MPs and induced new hydrophilic functional groups containing oxygen. Thus, the acute lethal toxicity of PLA MPs exhibited noteworthy increase, compared to before UV treatment after UV treatment, which was greater than that of UV-PE MPs. In addition, UV-PLA MPs showed markedly elevated reactive oxygen species concentration in D. magna compared to positive control. However, there was no significant increase in the level of lipid peroxidation, possibly due to successful defense by antioxidant enzymes (superoxide dismutase and catalase). These findings highlight the ecotoxicological risks of biodegradable MPs to aquatic organisms, which require comprehensive long-term studies.

Accelerated fragmentation of two thermoplastics (polylactic acid and polypropylene) into microplastics after UV radiation and seawater immersion.

To better understand the fate and assess the ingestible fraction of microplastics (by aquatic organisms), it is essential to quantify and characterize of their released from larger items under environmental realistic conditions. However, the current information on the fragmentation and size-based characteristics of released microplastics, for example from bio-based thermoplastics, is largely unknown. The goal of our work was to assess the fragmentation and release of microplastics, under ultraviolet (UV) radiation and in seawater, from polylactic acid (PLA) items, a bio-based polymer, and from polypropylene (PP) items, a petroleum-based polymer. To do so, we exposed pristine items of PLA and PP, immersed in filtered natural seawater, to accelerated UV radiation for 57 and 76 days, simulating 18 and 24 months of mean natural solar irradiance in Europe. Our results indicated that 76-day UV radiation induced the fragmentation of parent plastic items and the microplastics (50 - 5000 µm) formation from both PP and PLA items. The PP samples (48 ± 26 microplastics / cm2) released up to nine times more microplastics than PLA samples (5 ± 2 microplastics / cm2) after a 76-day UV exposure, implying that the PLA tested items had a lower fragmentation rate than PP. The particles' length of released microplastics was parameterized using a power law exponent (α), to assess their size distribution. The obtained α values were 3.04 ± 0.11 and 2.54 ± 0.06 (-) for 76-day UV weathered PP and PLA, respectively, meaning that PLA microplastics had a larger sized microplastics fraction than PP particles. With respect to their two-dimensional shape, PLA microplastics also had lower width-to-length ratio (0.51 ± 0.17) and greater fiber-shaped fractions (16%) than PP microplastics (0.57 ± 0.17% and 11%, respectively). Overall, the bio-based PLA items under study were more resistant to fragmentation and release of microplastics than the petroleum-based PP tested items, and the parameterized characteristics of released microplastics were polymer-dependent. Our work indicates that even though bio-based plastics may have a slower release of fragmented particles under UV radiation compared to conventional polymer types, they still have the potential to act as a source of microplastics in the marine environment, with particles being available to biota within ingestible size fractions, if not removed before major fragmentation processes.

Behavioral effects of polylactic acid microplastics on the tadpoles of Pelophylax nigromaculatus.

Polylactic acid microplastics (PLA-MPs), biobased plastics made from renewable resources, are considered to be a potential solution for alleviating the pollution pressure of plastics; however, the potential environmental risks of PLA-MPs must be further evaluated. In this study, the effects of PLA-MPs on the tadpoles of Pelophylax nigromaculatus were investigated by designing different PLA-MP exposure experiments. We found that PLA-MPs negatively affected the survival, growth and development of tadpoles. In addition, in open field tests, PLA-MPs also reduced tadpole locomotion while resulting in more repetitive searching behavior within a restricted area. This effect was more pronounced at higher concentrations of PLA-MPs (20 mg/mL) and in combination with the heavy metal Cd2+. In the tank tests, PLA-MPs increased tadpole aggregation, and their combined effect with Cd2+ resulted in a tendency for tadpole aggregation to increase and then decrease, with the distribution tending to favor aggregation in edge regions. PLA-MPs also strongly inhibited the spatiotemporal exploratory activities of tadpoles in the tanks. This study provides a more detailed investigation of the behavioral effects of PLA-MPs on tadpoles and provides a theoretical basis for subsequent ecotoxicological studies of PLA-MPs.

Bacterial community in the buckwheat rhizosphere responds more sensitively to single microplastics in lead-contaminated soil compared to the arbuscular mycorrhizal fungi community.

Soil pollution by microplastics (MPs), defined as plastic particles <5 mm, and heavy metals is a significant environmental issue. However, studies on the co-contamination effects of MPs and heavy metals on buckwheat rhizosphere microorganisms, especially on the arbuscular mycorrhizal fungi (AMF) community, are limited. We introduced low (0.01 g kg-1) and high doses of lead (Pb) (2 g kg-1) along with polyethylene (PE) and polylactic acid (PLA) MPs, both individually and in combination, into soil and assessed soil properties, buckwheat growth, and rhizosphere bacterial and AMF communities in a 40-day pot experiment. Notable alterations were observed in soil properties such as pH, alkaline hydrolyzable nitrogen (AN), and the available Pb (APb). High-dose Pb combined with PLA-MPs hindered buckwheat growth. Compared to the control, bacterial Chao1 richness and Shannon diversity were lower in the high dose Pb with PLA treatment, and differentially abundant bacteria were mainly detected in the high Pb dose treatments. Variations in bacterial communities correlated with APb, pH and AN. Overall, the AMF community composition remained largely consistent across all treatments. This phenomenon may be due to fungi having lower nutritional demands than bacteria. Stochastic processes played a relatively important role in the assembly of both bacterial and AMF communities. In summary, MPs appeared to amplify both the positive and negative effects of high Pb doses on the buckwheat rhizosphere bacteria.

Preparation of photoluminescent nano-biocomposite nacre from graphene oxide and polylactic acid.

Nano-biocomposites of inorganic and organic components wereprepared to produce long-persistent phosphorescent artificial nacre-like materials. Biodegradable polylactic acid (PLA), graphene oxide (GO), and nanoparticles (13-20 nm) of lanthanide-doped aluminate pigment (NLAP) were used in a simple production procedure of an organic/inorganic hybrid nano-biocomposite. Both polylactic acid and GO nanosheets were chemically modified to form covalent and hydrogen bonding. The high toughness, good tensile strength, and great endurance of those bonds were achieved by their interactions at the interfaces. Long-persistent and reversible photoluminescence was shown by the prepared nacre substrates. Upon excitation at 365 nm, the nacre substrates generated an emission peak at 517 nm. When ultraviolet light was shone on luminescent nacres, they displayed a bright green colour. The high superhydrophobicity of the generated nacres was obtained without altering their mechanical characteristics.

Nanocomposite microbeads made of recycled polylactic acid for the magnetic solid phase extraction of xenobiotics from human urine.

Nanocomposite microbeads (average diameter = 10-100 µm) were prepared by a microemulsion-solidification method and applied to the magnetic solid-phase extraction (m-SPE) of fourteen analytes, among pesticides, drugs, and hormones, from human urine samples. The microbeads, perfectly spherical in shape to maximize the surface contact with the analytes, were composed of magnetic nanoparticles dispersed in a polylactic acid (PLA) solid bulk, decorated with multi-walled carbon nanotubes (mPLA@MWCNTs). In particular, PLA was recovered from filters of smoked electronic cigarettes after an adequate cleaning protocol. A complete morphological characterization of the microbeads was performed via Fourier-transform infrared (FTIR) spectroscopy, UV-Vis spectroscopy, thermogravimetric and differential scanning calorimetry analysis (TGA and DSC), scanning electron microscopy (SEM) and X-ray diffraction analysis (XRD). The recovery study of the m-SPE procedure showed yields ≥ 64%, with the exception of 4-chloro-2-methylphenol (57%) at the lowest spike level (3 µg L-1). The method was validated according to the main FDA guidelines for the validation of bioanalytical methods. Using liquid chromatography-tandem mass spectrometry, precision and accuracy were below 11% and 15%, respectively, and detection limits of 0.1-1.8 µg L-1. Linearity was studied in the range of interest 1-15 µg L-1 with determination coefficients greater than 0.99. In light of the obtained results, the nanocomposite microbeads have proved to be a valid and sustainable alternative to traditional sorbents, offering good analytical standards and being synthetized from recycled plastic material. One of the main objectives of the current work is to provide an innovative and optimized procedure for the recycling of a plastic waste, to obtain a regular and reliable microstructure, whose application is here presented in the field of analytical chemistry. The simplicity and greenness of the method endows the procedure with a versatile applicability in different research and industrial fields.

Compact 3D-Printed Unit for Separation of Simple Gas Mixtures Combined with Chemiresistive Sensors.

Inexpensive chemiresistive sensors are often insufficiently selective as they are sensitive to multiple components of the gas mixture at the same time. One solution would be to insert a device in front of the sensor that separates the measured gas mixture and possibly isolates the unwanted components. This study focused on the fabrication and characterization of a compact unit, which was fabricated by 3D printing, for the separation and detection of simple gas mixtures. The capillary, the basic part of the compact unit, was 4.689 m long and had a diameter of 0.7 mm. The compact unit also contained a mixing chamber on the inlet side and a measuring chamber with a MiCS-6814 sensor on the outlet side. Mixtures of ethanol and water at different concentrations were chosen for characterization. The measured calibration curve was found to have a reliability of R2 = 0.9941. The study further addressed the elements of environmental friendliness of the materials used and their sustainability.

Influence of SiC and ZnO Doping on the Electrical Performance of Polylactic Acid-Based Triboelectric Nanogenerators.

Polylactic acid (PLA) is one of the most widely used materials for fused deposition modeling (FDM) 3D printing. It is a biodegradable thermoplastic polyester, derived from natural resources such as corn starch or sugarcane, with low environmental impact and good mechanical properties. One important feature of PLA is that its properties can be modulated by the inclusion of nanofillers. In this work, we investigate the influence of SiC and ZnO doping of PLA on the triboelectric performance of PLA-based tribogenerators. Our results show that the triboelectric signal in ZnO-doped PLA composites increases as the concentration of ZnO in PLA increases, with an enhancement in the output power of 741% when the ZnO concentration in PLA is 3 wt%. SiC-doped PLA behaves in a different manner. Initially the triboelectric signal increases, reaching a peak value with enhanced output power by 284% compared to undoped PLA, when the concentration of SiC in PLA is 1.5 wt%. As the concentration increases to 3 wt%, the triboelectric signal reduces significantly and is comparable to or less than that of the undoped PLA. Our results are consistent with recent data for PVDF doped with silicon carbide nanoparticles and are attributed to the reduction in the contact area between the triboelectric surfaces.

Improvement of Osteogenic Differentiation of Mouse Pre-Osteoblastic MC3T3-E1 Cells on Core-Shell Polylactic Acid/Chitosan Electrospun Scaffolds for Bone Defect Repair.

Electrospun hybrid scaffolds composed of synthetic and natural polymers have gained increasing interest in tissue engineering applications over the last decade. In this work, scaffolds composed of polylactic acid electrospun fibers, either treated (P-PLA) or non-treated (PLA) with air-plasma, were coated with high molecular weight chitosan to create a core-shell microfibrous structure. The effective thickness control of the chitosan layer was confirmed by gravimetric, spectroscopic (FTIR-ATR) and morphological (SEM) investigations. The chitosan coating increased the fiber diameter of the microfibrous scaffolds while the tensile mechanical tests, conducted in dry and wet environments, showed a reinforcing action of the coating layer on the scaffolds, in particular when deposited on P-PLA samples. The stability of the Chi coating on both PLA and P-PLA substrates was confirmed by gravimetric analysis, while their mineralization capacity was evaluated though scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) after immersing the scaffolds in simulated body fluids (SBF) at 37 °C for 1 week. Sample biocompatibility was investigated through cell viability assay and SEM analysis on mouse pre-osteoblastic MC3T3-E1 cells grown on scaffolds at different times (1, 7, 14 and 21 days). Finally, Alizarin Red assay and qPCR analysis suggested that the combination of plasma treatment and chitosan coating on PLA electrospun scaffolds influences the osteoblastic differentiation of MC3T3-E1 cells, thus demonstrating the great potential of P-PLA/chitosan hybrid scaffolds for bone tissue engineering applications.

Effect of Poly(propylene carbonate) on Properties of Polylactic Acid-Based Composite Films.

To enrich the properties of polylactic acid (PLA)-based composite films and improve the base degradability, in this study, a certain amount of poly(propylene carbonate) (PPC) was added to PLA-based composite films, and PLA/PPC-based composite films were prepared by melt blending and hot-press molding. The effects of the introduction of PPC on the composite films were analyzed through in-depth studies on mechanical properties, water vapor and oxygen transmission rates, thermal analysis, compost degradability, and bacterial inhibition properties of the composite films. When the introduction ratio coefficient of PPC was 30%, the tensile strength of the composite film increased by 19.68%, the water vapor transmission coefficient decreased by 14.43%, and the oxygen transmission coefficient decreased by 18.31% compared to that of the composite film without PPC, the cold crystallization temperature of the composite film increased gradually from 96.9 °C to 104.8 °C, and PPC improved the crystallization ability of composite film. The degradation rate of the composite film with PPC increased significantly compared to the previous one, and the degradation rate increased with the increase in the PPC content. The degradation rate was 49.85% and 46.22% faster on average than that of the composite film without PPC when the degradation was carried out over 40 and 80 days; the composite film had certain inhibition, and the maximum diameter of the inhibition circle was 2.42 cm. This study provides a strategy for the development of PLA-based biodegradable laminates, which can promote the application of PLA-based laminates in food packaging.

Ring Opening Polymerization of Six- and Eight-Membered Racemic Cyclic Esters for Biodegradable Materials.

The low percentage of recyclability of the polymeric materials obtained by olefin transition metal (TM) polymerization catalysis has increased the interest in their substitution with more eco-friendly materials with reliable physical and mechanical properties. Among the variety of known biodegradable polymers, linear aliphatic polyesters produced by ring-opening polymerization (ROP) of cyclic esters occupy a prominent position. The polymer properties are highly dependent on the macromolecule microstructure, and the control of stereoselectivity is necessary for providing materials with precise and finely tuned properties. In this review, we aim to outline the main synthetic routes, the physical properties and also the applications of three commercially available biodegradable materials: Polylactic acid (PLA), Poly(Lactic-co-Glycolic Acid) (PLGA), and Poly(3-hydroxybutyrate) (P3HB), all of three easily accessible via ROP. In this framework, understanding the origin of enantioselectivity and the factors that determine it is then crucial for the development of materials with suitable thermal and mechanical properties.

The degradation of polylactic acid face mask components in different environments.

The disposal of fossil fuel-based plastics poses a huge environmental challenge, leading to increased interest in biodegradable alternatives such as polylactic acid (PLA). This study focuses on the environmental impact and degradation of PLA face mask components under various conditions (UV (Ultraviolet) radiation, DI water, landfill leachate of various ages, seawater, and enzyme). Under UV exposure, notable changes in physicochemical properties were observed in the PLA masks, including increased oxidation over time. Degradation rates varied across environments, with old landfill leachate and enzyme degradation having a notable impact, especially on meltblown layers. Furthermore, it was found that seawater conditions hampered the degradation of PLA masks, likely due to the inhibitory effect of high salt concentrations. The pathways of chemical group changes during degradation were elucidated using 2D-COS (Two-Dimensional Correlation Spectroscopy) maps. The investigation into the release of microparticles and oligomers further revealed the degradation mechanism. Moreover, PLA masks were found to release fewer microparticles when degraded in studied environments when compared to traditional polypropylene masks. Furthermore, correlation analysis highlighted the influence of factors such as carbonyl index and contact angle on degradation rates, underscoring the complex interplay between environmental conditions and PLA degradation. This comprehensive investigation advances the understanding of PLA degradation pathways, which are crucial for mitigating plastic pollution and promoting the development of sustainable products.

Biodegradable Polymers in Veterinary Medicine-A Review.

During the past two decades, tremendous progress has been made in the development of biodegradable polymeric materials for various industrial applications, including human and veterinary medicine. They are promising alternatives to commonly used non-degradable polymers to combat the global plastic waste crisis. Among biodegradable polymers used, or potentially applicable to, veterinary medicine are natural polysaccharides, such as chitin, chitosan, and cellulose as well as various polyesters, including poly(ε-caprolactone), polylactic acid, poly(lactic-co-glycolic acid), and polyhydroxyalkanoates produced by bacteria. They can be used as implants, drug carriers, or biomaterials in tissue engineering and wound management. Their use in veterinary practice depends on their biocompatibility, inertness to living tissue, mechanical resistance, and sorption characteristics. They must be designed specifically to fit their purpose, whether it be: (1) facilitating new tissue growth and allowing for controlled interactions with living cells or cell-growth factors, (2) having mechanical properties that address functionality when applied as implants, or (3) having controlled degradability to deliver drugs to their targeted location when applied as drug-delivery vehicles. This paper aims to present recent developments in the research on biodegradable polymers in veterinary medicine and highlight the challenges and future perspectives in this area.

Fabrication of 3D-printed scaffolds loaded with gallium acetylacetonate for potential application in osteoclastic bone resorption.

We recently reported the potential of a new gallium compound, gallium acetylacetonate (GaAcAc) in combating osteoclastic bone resorption through inhibition of osteoclast differentiation and function. Herein, we focused on 3D-printed polylactic acid scaffolds that were loaded with GaAcAc and investigated the impact of scaffold pretreatment with polydopamine (PDA) or sodium hydroxide (NaOH). We observed a remarkable increase in scaffold hydrophilicity with PDA or NaOH pretreatment while biocompatibility and in vitro degradation were not affected. NaOH-pretreated scaffolds showed the highest amount of GaAcAc loading when compared to other scaffolds (p < 0.05). NaOH-pretreated scaffolds with GaAcAc loading showed effective reduction of osteoclast counts and size. The trend was supported by suppression of key osteoclast differentiation markers such as NFAT2, c-Fos, TRAF6, & TRAP. All GaAcAc-loaded scaffolds, regardless of surface pretreatment, were effective in inhibiting osteoclast function as evidenced by reduction in the number of resorptive pits in bovine cortical bone slices (p < 0.01). The suppression of osteoclast function according to the type of scaffold followed the ranking: GaAcAc loading without surface pretreatment > GaAcAc loading with NaOH pretreatment > GaAcAc loading with PDA pretreatment. Additional studies will be needed to fully elucidate the impact of surface pretreatment on the efficacy and safety of GaAcAc-loaded 3D-printed scaffolds.

Concomitant Delivery of Pirarubicin and Salinomycin Synergistically Enhanced the Efficacy of Cancer Therapy and Reduced the Risk of Cancer Relapse.

Pirarubicin attracted considerable attention in clinical studies because of its high therapeutic efficacy and reduced toxicity in comparison with other anthracyclines. Nevertheless, ~ 30% patients undergoing PIRA treatment still experience relapse and metastasis. Clinical advancements unveiled that cancer stem cells (CSCs) residing in the tumor constitutes a major factor for such limitations and subsequently are the reason for treatment failure. Consequently, eradicating CSCs alongside bulk tumor is a crucial undertaking to attain utmost therapeutic efficacy of the treatment. Nevertheless, majority of the CSCs inhibitors currently under examination lack specificity, show unsynchronized bioavailability with other primary treatments and exhibit notable toxicity in their therapeutic applications, which is primarily attributable to their inadequate tumor-targeting capabilities. Therefore, we have developed a biodegradable polylactic acid based blend block copolymeric NPs for concomitant delivery of CSCs inhibitor Salinomycin (SAL) & chemotherapeutic drug Pirarubicin (PIRA) with an aim to improve the efficacy of treatment and prevent cancer relapse. Prepared NPs showed < 100 nm size and excellent loading with sustained release for both the drugs. Also, PIRA:SAL co-loaded NPs exhibits synergistically enhanced cytotoxicity against cancer cell as well as CSCs. Most importantly, NPs mediated co-delivery of the drugs showed complete tumor eradication, without any reoccurrence throughout the surveillance period. Additionally, NPs treatment didn't show any histopathological alteration in vital organs confirming their non-toxic nature. Altogether, present study concludes that the developed PIRA:SAL NPs have excellent efficacy for tumor regression as well as prevention of cancer relapse, hence can be used as a potential combination therapy for cancer treatment.