Search Results (2,161)

Introduction: In this study, we aimed to optimize the microfluidizer-based preparation of poly(lactic-co-glycolic acid) nano-micelles (PLGANM), increasingly used for parenteral delivery of poorly water-soluble drugs but typically exhibiting poor physical stability when produced by conventional methods. Method: By systematically tuning microfluidization (MFZ) parameters, we demonstrate an efficient strategy to enhance PLGANM stability and ensure robust, scalable manufacturing, relevant for long-term storage and clinical translation applications. The influence of several key factors designed by Central Composite Design (CCD), including the amount of PLGA and Tween 80, homogenization pressure, and number of passes of MFZ on the size, polydispersity (measured by DLS), and hence stability of the PLGANM, was analyzed for 60 days. 60 PLGANMs produced by the MFZ method (PMFZ) were compared with the PLGANM consisting of equivalent amounts of PLGA and T80 produced using the traditional oil-in-water method (POW). Desired limits were set to minimize standard deviations for Z-average, Zeta Potential, and PDI. Results: Coded variables for optimized PMFZ (OPMFZ) were found to be 82.96 mg PLGA, 6.78 mL 5% T80, 11,000 psi pressure, and 1 pass. Conclusions: This study demonstrates that microfluidization, when guided by a QbD framework, offers precise control over particle attributes and enables reproducible production of stable PLGANM. Full article

Poly(lactic acid) (PLA) has strong potential for use in sustainable packaging, automotive components, and structural materials; however, its inherent brittleness and limited thermal stability restrict broader application. To overcome these drawbacks, this study developed PLA-based composites reinforced with mica and compatibilized using poly(vinyl butyral) (PVB). To overcome the inherent brittleness and limited thermal stability of poly(lactic acid) (PLA), this study investigated the incorporation of mica as a reinforcing filler into PLA and PLA/poly(vinyl butyral) (PVB) composite systems. Five types of mica with varying particle sizes and densities were examined to evaluate their influence on the mechanical, thermal, and rheological properties of the composites. The PLA/PVB blend was prepared in an 8:2 weight ratio, and mica was added at 5 phr (35 g). PLA/mica composites showed limited improvement in mechanical performance due to poor interfacial compatibility between PLA and mica, resulting in decreased tensile strength and non-uniform filler dispersion. In contrast, the addition of PVB, a tough and flexible polymer containing hydroxyl groups (ca. 20 mol%) remaining after polymerization, significantly enhanced the interfacial interaction with mica and improved filler dispersion within the matrix. As a result, PLA/PVB/mica composites exhibited increased tensile strength and toughness. Thermal analysis revealed that mica restricted polymer chain mobility, leading to higher glass transition temperatures, while PVB promoted a more uniform crystalline structure. Rheological studies indicated that PLA/PVB/mica composites had higher complex viscosity and lower melt flow index (MFI) due to increased molecular interactions and reduced chain mobility. Notably, certain mica types containing Ca²⁺ ions catalyzed chain scission during melt processing, leading to reduced molecular weight and increased MFI. These findings demonstrate that the synergistic combination of PVB and mica can effectively improve the processability and performance of PLA-based composites, offering a promising route for developing sustainable materials for advanced applications. Full article

Anterior cruciate ligament (ACL) rupture causes joint instability and increases the risk of osteoarthritis due to the ligament’s limited healing capacity. Silk, particularly from Bombyx mori, combines high cytocompatibility with robust biomechanical properties. Its main components are fibroin and sericin, with the latter usually being removed to reduce immunogenicity and improve biocompatibility. Silk threads were processed either as raw silk (designated as “untreated”) or subjected to a patented degumming procedure (DE102021118652A1) to obtain purified silk. Both variants were used alone or in combination with poly(L-lactic acid-co-caprolactone) (P(LA-CL)) fibers, yielding four scaffold groups: untreated silk, purified silk, untreated silk/P(LA-CL), and purified silk/P(LA-CL). Three-layer scaffolds were fabricated using a zigzag embroidery pattern. Structural analysis revealed scaffold porosity of ≈38% for silk, ≈46% for purified silk, and up to ≈70% for scaffolds containing P(LA-CL). Uniaxial tensile testing showed that purified silk scaffolds achieved the highest maximum force at break (≈684 N), whereas elongation at maximum force was limited in the hybrid scaffolds—silk/P(LA-CL) ≈ 28% and p-silk/P(LA-CL) ≈ 32%—despite the high intrinsic extensibility of P(LA-CL). All scaffolds supported cell adhesion and showed no cytotoxicity. P-silk and p-silk/P(LA-CL) scaffolds exhibited the highest fibroblast adherence and pronounced paxillin expression, indicating strong cell–material interactions. Gene expression of ligament-related ECM components and connexin 43 was maintained across all groups. These results demonstrate that embroidered silk fibroin scaffolds provide a reproducible architecture with tunable porosity and mechanical properties, supporting fibroblast colonization and ligament-specific ECM expression. Such scaffolds represent promising candidates for ACL tissue engineering and future graft development. Full article

Second cheese whey (SCW), a major by-product of ricotta cheese production, poses significant environmental challenges due to its high organic load. Biohydrogen (bio-H₂) and poly-β-hydroxybutyrate (PHB) production offer a sustainable reuse of SCW, that provides ideal nutrients for microbial growth. This study aimed to convert SCW into Bio-H₂ and PHB using a 5-liter tubular bioreactor in a sequential lactic fermentation and photofermentation system. Two lighting conditions were tested: white LED (WL) and selected LED (SL). Optimal results were achieved with a co-inoculum of Lactococcus lactis MK L84 and Lacticaseibacillus paracasei MK L49 at pH 4.5–5.5, followed by photofermentation with Rhodopseudomonas palustris 42OL under SL condition. The process yielded an average of 0.47 L of H₂ per liter of substrate and 1.66% wPHB/wCDW. This approach successfully transformed dairy waste into high-value products, promoting circular economy principles. Full article

This work investigates the modification of poly(lactic acid) (PLA) film properties for food packaging applications through the incorporation of modified gelatin (Gel-mod) and a choline chloride/glycerol deep eutectic solvent (DES). PLA/Gel-mod/DES materials were melt-processed and evaluated with respect to structure, morphology, thermal and mechanical behavior, processability, wettability, barrier performance, and compostability. Two incorporation routes were investigated for adding Gel-mod into the PLA matrix: direct incorporation and masterbatch preparation. FTIR and SEM analyses confirmed improved interfacial interactions and more homogeneous dispersion when Gel-mod was directly incorporated, compared with the masterbatch route. DES acted as an effective plasticizer and nucleating agent, reducing Tg, increasing crystallinity, and enhancing processability while maintaining thermal stability. Mechanical properties decreased relative to neat PLA, primarily due to increased crystallinity and chain scission. PLA_4Gel-mod demonstrated a more balanced performance, with higher elongation at break and improved processability than the other formulations, likely due to its single processing cycle, which minimized PLA degradation. Increased hydrophilicity led to higher water vapor transmission rates, correlating with accelerated biodegradation. Overall, the synergistic incorporation of DES and gelatin provides a viable strategy to tailor PLA properties, enabling the development of compostable packaging films suitable for sustainable food contact applications. Full article

Background/Objectives: Biodegradable implants have emerged as a promising alternative to traditional metallic fixation devices in pediatric orthopedic surgery. Avoiding implant removal is especially advantageous in children, who would otherwise require a second operation with additional anesthetic and surgical risks. This study reviews the current use of poly(lactic-co-glycolic acid) (PLGA) implants in pediatric fracture fixation and evaluates how they address limitations associated with traditional hardware. Methods: A narrative review was conducted summarizing current evidence, clinical experience, and case examples involving PLGA-based devices used in pediatric trauma. Special emphasis was placed on the degradation mechanism of PLGA, its controlled hydrolysis profile, and the capacity of the material to provide temporary mechanical stability during bone healing before complete resorption. The review included studies of PLGA use in forearm, distal radius, ankle, and elbow fractures, comparing outcomes to those obtained with metallic implants. Results: Across multiple clinical reports and case series, PLGA implants demonstrated effective fracture healing, stable fixation, and complication rates comparable to traditional metallic devices. Patients treated with resorbable implants benefited from reduced postoperative morbidity, no requirement for implant removal, and improved imaging compatibility. Conclusions: PLGA-based bioabsorbable implants represent a safe and effective alternative to conventional metal fixation in children. Their favorable degradation kinetics and clinical performance support their growing use in pediatric trauma surgery, while ongoing advances in polymer design and bioresorbable alloys continue to expand future applications. Full article

Age-associated hair loss is primarily driven by decreased function and proliferation of hair follicle stem cells (HFSCs), often exacerbated by increased inhibitory signaling and changes in the stem cell niche. Macrophage polarization to the anti-inflammatory M2 phenotype is known to increase stem cell proliferation. We investigated the effects of poly-D,L-lactic acid (PDLLA) on hair growth in middle-aged skin, focusing on its role in modulating macrophage polarization and HFSC activity. Senescent macrophages were analyzed for Piezo1 activity, macrophage polarization, and secretion of hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) after PDLLA treatment. Downstream effects on HFSC proliferation, stemness, and Wnt signaling were assessed, including inhibition experiments using the Piezo1 blocker GsMTx4. In vivo analyses assessed hair follicle number, diameter, length, anagen duration, and hair coverage following PDLLA administration in middle-aged mice. PDLLA increased Piezo1 expression and activity in senescent macrophages, enhancing M2 polarization and secretion of HGF and IGF-1. This activated the RAS/ERK signaling pathway, promoting HFSC proliferation and stemness. Furthermore, PDLLA upregulated Wnt signaling molecules (Wnt3a, Wnt10b, and β-catenin) and anagen phase-related factor (Axin2, LEF1, and Lgr5), which were decreased by GsMTX4. In middle-aged animal skin, PDLLA administration led to increased hair follicle number, diameter, and length, as well as prolonged anagen and greater hair coverage. Collectively, these findings suggest that PDLLA rejuvenates the middle-aged skin microenvironment, at least in part through Piezo1-associated M2 macrophage polarization and enhanced HFSC function, offering a promising therapeutic strategy for age-related hair loss targeting both the immune and the stem cell compartments. Full article

Background: Wounds with an avascular component represent a significant challenge in medical care due to impaired blood flow. Synthetic matrices, such as poly-lactic acid (PLA), have demonstrated promising results in promoting wound healing in complex wounds, including those with restricted blood supply, such as diabetic foot and venous leg ulcers. Objective: This case series presents the outcomes of five patients with wounds containing exposure of avascular components, of various etiologies successfully treated with PLA matrices. Case description: Five patients presented complex wounds involving exposure of bone, tendon, fascia, or osteosynthetic material. Wound bed preparation included debridement followed by PLA application covered with additional layers (non-adherent dressing, absorbent dressing, and compression bandage) as needed. Weekly assessments were conducted until full wound closure was achieved. Results: All cases showed successful outcomes, with PLA promoting granulation tissue formation and re-epithelialization, contributing to wound closure. One patient required skin grafts for complete healing. No local infections were reported before or after PLA application. Conclusions: PLA matrices are a practical and effective option for managing complex wounds, promoting tissue regeneration and optimizing wound bed quality for skin grafts or flaps. While these findings are promising, further studies are needed to confirm the broader applicability and efficacy of PLA in the management of wounds containing exposure of avascular structures. Full article

Poly (lactic-co-glycolic acid) (PLGA) is a widely used copolymer with applications across medical, pharmaceutical, and other industrial fields. Its biodegradability and biocompatibility make it one of the most versatile polymers for nanoscale drug delivery. The present review addresses current knowledge and recent advances in PLGA-based co-delivery nanoformulations with a special reference to design strategies, functional mechanisms, and translational potential. Conventional and advanced fabrication methods, the structural design of PLGA-based nanocarriers, approaches to scale-up and reproducibility, classification of co-delivery types, mechanisms governing drug release, surface modification and functionalization are all discussed. Special attention is given to PLGA-based co-delivery systems, encompassing drug–drug, drug–gene, gene–gene and multi-modal combinations, supported by recent studies demonstrating synergistic therapeutic outcomes. The review also examines clinical translation efforts and the regulatory landscape for PLGA-based nanocarriers. Unlike most existing reviews that typically focus either on PLGA fundamentals or on co-delivery approaches in isolation, this article bridges these domains by providing an integrated, comparative analysis of PLGA-based co-delivery systems and elucidating a critical gap in linking design strategies with translational requirements. In addition, by emphasising the relevance of PLGA-based co-delivery for combination therapies, particularly in cancer and other complex diseases, the review highlights the strong clinical and translational potential of these platforms. Key challenges, such as reproducibility, large-scale manufacturing, and complex regulatory pathways, are discussed alongside emerging trends and future perspectives. Taken together, this review positions PLGA-based co-delivery strategies as a critical driver for advancing precision therapeutics and shaping the future landscape of nanomedicine. Full article

Fused filament fabrication (FFF) is a widely used material extrusion-based 3D printing process known for its cost-effectiveness, versatility, and ability to produce intricate components. However, the strength of interlayer bonding is significantly influenced by printing parameters, material characteristics, and the chosen printing paths. The present study employs a custom response surface design derived from an L9 orthogonal array to strictly investigate the impact of three distinct infill patterns under varying printing temperatures and printing speeds on the responses of flexural strength, σ_b, and elasticity modulus, E (MPa). Flat-oriented poly-lactic acid (PLA) specimens were subjected to three-point bending tests to evaluate flexural strength for 100% infill rates and a 0.2 mm layer height. Besides the experimental investigation and the statistical analysis, failure modes of the fractured samples were observed to correlate the independent printing parameters with the aforementioned response. The desirability function was employed to identify the set of optimal parameters for maximizing the flexural strength and elasticity modulus for the particular PLA material brand examined. The results indicated that infill pattern and printing speed have significant impact on both responses. The optimal parameters were identified as “centroid” for infill style, 203.03 °C for printing temperature and 25 mm/s for printing speed. Full article

Background/Objectives: Neovascular age-related macular degeneration (nAMD) poses a serious threat to the eyesight of older adults, representing a leading cause of irreversible vision loss. Anti-vascular endothelial growth factor (anti-VEGF) treatments are effective but require repeated intraocular injections and show poor responses in some patients. CGK012 is a novel derivative of decursin that inhibits the Wnt/β-catenin pathway. This study aimed to elucidate the mode of action of CGK012 and examine its therapeutic effects. Methods: We performed in vitro cellular studies in a retinal pigment epithelial (RPE) cell line (ARPE-19) and human umbilical vein endothelial cells (HUVECs). We examined the in vivo efficacy of CGK012-loaded implants in laser-induced choroidal neovascularization (CNV) rabbit models. We also determined the implants’ in vitro dissolution, intraocular release, and disposition characteristics. Results: CGK012 decreased angiogenic/proinflammatory factor expression and suppressed the epithelial–mesenchymal transition (EMT) in RPE cells by promoting intracellular β-catenin degradation. Additionally, it repressed the expression of cyclin D1 and c-myc, downstream target genes of β-catenin, and inhibited HUVEC capillary tube formation. CGK012-loaded poly (lactic-co-glycolic acid) (PLGA) intravitreal implants significantly reduced vascular leakage in a laser-induced CNV rabbit model. Notably, CGK012 released from the implant was highly permeable to retina/choroid tissue and downregulated β-catenin, angiogenic/inflammatory factors, and vimentin in the rabbit model. The CGK012 concentration reached a plateau at 28–42 days in the vitreous humor and decayed with a half-life of 14 days without systemic exposure. Conclusions: Our findings demonstrate that CGK012 implants prevent choroidal neovascularization through the Wnt/β-catenin pathway suppression and produce high concentrations of CGK012 in the posterior eye segment with prolonged release. Thus, these implants provide more therapeutic choices for nAMD treatment. Full article

Background/Objectives: Though ototoxic, cisplatin is a mainstay of chemotherapy for a variety of cancers. One suggested mechanism of cisplatin ototoxicity involves damage to the spiral ganglion afferent neurons in the inner ear. There is a need for a high-throughput model to screen medications for efficacy against cisplatin and to develop a local therapeutic to mitigate cisplatin’s debilitating side effects. Microparticles encapsulating a therapeutic medication are an injectable and tunable method of sustained drug delivery, and thus a promising treatment. Methods: SH-SY5y human neuroblastoma cells were used as a cell line model for the spiral ganglion neurons. The cells were dosed with cisplatin and four potential therapeutics (melatonin, metformin, cyclosporine, and N-acetylcysteine), with cell viability measured by CCK-8 assay. The most promising therapeutic, N-acetylcysteine (NAC), was then encapsulated into multiple poly(lactic-co-glycolic acid) (PLGA) microparticle subtypes of varied lactide–glycolide (L:G) ratios and NAC amounts. The elution profile of each microparticle subtype was determined over two months. Results: Of the therapeutics screened, only cells dosed with 1 or 10 mM NAC prior to cisplatin injury demonstrated an improvement in cell viability (73.8%, p < 1 × 10⁻⁸) when compared to cells dosed with cisplatin alone. The 75:25 L:G microparticles demonstrated an increase in the amount of NAC released compared to the 50:50 L:G microparticles. Conclusions: NAC is a potential therapeutic agent for cisplatin toxicity when tested in a neuronal cell line model. NAC was encapsulated into PLGA microparticles and eluted detectable concentrations of NAC for 6 days, which is a first step towards otoprotection for the weeks long duration of chemotherapy treatment. This work describes a method of screening potential therapeutics and a strategy to develop local drug eluting treatments to protect against cisplatin ototoxicity. Full article

The increasing use of biodegradable plastics derived from renewable sources (PLA, PHB, PBAT, and others) in the packaging industry raises controversies and risks related to potentially integrating these plastics into municipal waste streams, which may significantly hinder future recycling efforts. This publication addresses this issue by investigating a selected bio-based and biodegradable commercial mixture of poly(lactic acid) and poly(butylene adipate terephthalate) (PLA/PBAT), referred to as (BIO), in blends with polypropylene (PP) and polystyrene (PS). The blends were prepared with three different mass contents of 1, 5, and 10 wt.% using (PP) and (PS) as base materials. The effects of introducing biodegradable and bio-based plastics into municipal waste streams (PCR—Post-Consumer Recycling), which typically contain polypropylene, various grades of polyethylene, and polystyrene, remain unknown. The purpose of the study was to assess the consequences of contaminating municipal waste destined for recycling (using PP and PS as examples) with small amounts (between 1 and 10%) of BIO plastics. The designed experiment and the obtained results simulate the expected presence of BIO contamination in future PP and PS recyclates. The prepared mixtures were subjected to injection molding to produce test specimens, which were then analyzed for changes in their physical properties such as tensile strength, impact strength and hardness. Thermal properties were assessed using Differential Scanning Calorimetry (DSC), while dynamic properties were analyzed at variable temperatures using Dynamic Mechanical Thermal Analysis (DMTA). The tests provided insights into how the addition of selected, but insignificant ratios (of 1 to 10%) of biopolymers affects the properties of (PP) and (PS) compared to materials without content of biopolymers. The conducted tests of mechanical properties (static and dynamic) and thermomechanical properties have shown that the change in the properties of the mixture depends not only on the amount of biodegradable polymer but also on the nature of the load. It would be advisable to analyze mechanical properties in relation to the duration of the load; therefore, a long-term load analysis is necessary. For dynamic tests, a decrease in impact strength was demonstrated with increasing biodegradable polymer content in the produced mixtures. Similar behavior was recorded for hardness measurements. The results underscore the need for continued research, given the valuable findings for processors and the advancement of mechanical recycling technologies. Full article

Tendon injuries present significant clinical challenges due to limited intrinsic healing and complex pathological mechanisms. Here, we developed a novel 3D bioprinted methacrylated type I collagen (ColMA) scaffold integrated with Growth Differentiation Factor-5 (GDF-5)-loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticles and dynamically cultured it under perfusion to establish a tenogenic microenvironment in vitro. Pathological human Tendon Stem/Progenitor Cells (hTSPCs) derived from tendinopathic surgical explants were encapsulated to investigate their impaired extracellular matrix (ECM) deposition and associated pro-inflammatory signaling. GDF-5-loaded nanoparticles (average diameter 140 ± 40 nm) were fabricated via microfluidic-assisted nanoprecipitation and homogeneously incorporated within the ColMA synthetic ECM to enable sustained growth factor release. Continuous perfusion culture (1 mL/min) ensured efficient mass transfer and supported cell viability above 70% over 21 days. Pathological hTSPCs exhibited impaired ECM remodeling, characterized by the absence of type I collagen and a 2.56-fold increase in type III collagen at day 7, indicative of a fibrotic-like phenotype. Western blot densitometry demonstrated a 5.31-fold elevation in secreted tenomodulin at day 14, while ECM analysis verified a type III to type I collagen ratio of 4.5. In addition, a markedly pro-inflammatory cytokine profile was observed, with elevated secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8) from day 7 onward, consistent with the chronic inflammatory status of cells derived from pathological tendon tissues. This modular 3D platform represents a robust in vitro model for mechanistic studies and the advancement of personalized regenerative strategies targeting chronic tendon disorders. Full article