Search Results (740)

Aging-related decline involves changes in oxidative stress, inflammation, mitochondrial function, telomere maintenance, metabolic regulation, and extracellular matrix homeostasis. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement and searched PubMed, Scopus, Embase, and Web of Science for English-language studies published from 1993 to 2025. Twelve primary studies met the eligibility criteria: four randomized clinical studies, four animal studies, one in vitro mechanistic study, and three delivery-system/formulation studies. Risk of bias was assessed using Cochrane Risk of Bias 2 (RoB 2), the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool, and a review-specific domain-based checklist informed by the National Toxicology Program/Office of Health Assessment and Translation framework. Representative compounds, including resveratrol, astragaloside IV, Ganoderma lucidum polysaccharide, epigallocatechin-3-gallate (EGCG) and betulinic acid, were associated with mitochondrial regulation, antioxidant defense, cytoskeletal stability, gut–brain signaling, extracellular-matrix protection, and longevity-related signaling. Nanoliposomes and poly(lactic-co-glycolic acid) (PLGA) nanoparticles improved selected stability, penetration, and pharmacokinetic outcomes. However, the evidence base was heterogeneous and predominantly preclinical; human evidence was limited to four relatively small studies, and certainty ranged from moderate to very low. The findings support mechanistic and translational potential but do not establish definitive anti-aging efficacy in humans. Full article

Orthodontic adhesives can accumulate biofilm, which may lead to long-term white-spot lesions; however, incorporating poly (lactic-co-glycolic acid) (PLGA) nanoparticles could improve their anticariogenic properties. Objective: To develop PLGA nanoparticles containing antiseptic agents for orthodontic adhesives, improve antibacterial activity against Streptococcus mutans, and assess cytotoxicity in gingival fibroblasts. Methods: PLGA nanoparticles with chlorhexidine and chitosan were synthesized and characterized using FTIR, SEM, and UV-Vis spectroscopy. Antibacterial activity was evaluated by agar diffusion and microdilution assays, and cytotoxicity and microhardness were also assessed. Results: PLGA-NPs showed moderate antibacterial effects, with inhibition rates from 74.25% to 54.05% in agar diffusion and reduced activity in microdilution (CC50: 3.75 µg/mL in adhesive, 15 µg/mL free). PLGA-NPs-CHx exhibited stronger antibacterial activity, with inhibition ranging from 89.38% to 73.75% and a CC50 of 0.93 µg/mL in both forms. PLGA-NPs-CH also showed significant inhibition (83.11% to 69.39%) and a CC50 of 1.87 µg/mL in adhesive and 7.5 µg/mL free. Vickers microhardness values were similar across groups: 74.67 HV for adhesive only, 74.11 HV for adhesive with PLGA-NPs, 74.22 HV for PLGA-NPs-CH-Adh, and 74 HV for PLGA-NPs-CHx-Adh. Conclusions: Incorporating PLGA nanoparticles functionalized with antiseptic agents into orthodontic adhesives shows promising antibacterial potential and may benefit orthodontic practice. Full article

Background: Osteoarthritis (OA), affecting approximately 240 million people worldwide, currently lacks targeted, long-acting therapeutic options. This study investigates how physicochemical properties (i.e., size, surface charge, polydispersity) influence poly(lactic-co-glycolic acid) (PLGA) microsphere (MS) diffusion into articular cartilage for enhanced corticosteroid delivery. Methods: PLGA MSs were synthesized via oil/water emulsions to create a variety of sizes and surface charges. MSs were loaded with corticosteroid (H-17-B) and release kinetics were studied in vitro and analyzed via HPLC. Diffusion of the MSs was investigated via a bovine explant model. Results: Unmodified PLGA MSs (approximately 0.58–0.98 µm) were synthesized via single-stage oil/water emulsion with varying poly(vinyl alcohol) concentrations and sonication intensities. All formulations exhibited near-neutral surface charges (−0.27 to 4.28 mV). Smaller particles achieved greater cartilage penetration, with bi-exponential diffusion models (R² = 0.706–0.999) outperforming classical Fickian approaches. However, multi-timepoint validation demonstrated fundamentally non-diffusive transport, likely governed by steric exclusion from the dense collagen network (0.05–0.06 µm pore size). Surface functionalization with avidin/palmitic acid or polyethylene glycol (PEG)/biotin yielded microspheres with controlled properties (0.36–0.97 µm; PDI: 0.10–0.32). In vitro release studies with hydrocortisone-17-butyrate (H-17-B; encapsulation efficiency of 79.8% ± 4.8%) demonstrated biphasic kinetics best fit by bi-exponential models (R² > 0.95). Unmodified microspheres exhibited 7.1% cumulative release by Day 14. High-performance liquid chromatography revealed that H-17-B undergoes ester hydrolysis to hydrocortisone during release, with surface modifications significantly affecting drug stability. Specifically, PEGylated microspheres maintained 96% of the drug in H-17-B form at Day 14 compared to only 37% for unmodified particles. Release was governed by PLGA degradation with concentration-independent kinetics, enabling predictable dose scalability. Conclusions: This work establishes that the behavior of PLGA microspheres in cartilage is controlled by size, charge, and surface functionalization. Surface modifications overcome physical barriers while stabilizing the encapsulated corticosteroid against premature hydrolysis, providing a framework for designing intra-articular drug delivery systems for osteoarthritis treatment. Full article

The production of polymeric nanoparticles using microfluidic systems holds great potential for controlled drug delivery applications. In this study, the effects of flow parameters and surfactant properties on the characteristics of PLGA (Poly (lactic-co-glycolic acid)) nanoparticles were systematically investigated. First, the total flow rate (TFR) and flow rate ratio (FRR) were optimized to ensure stable droplet formation. Subsequently, the effects of different surfactant types (anionic, cationic, and nonionic) and their varying concentrations were evaluated. Using the selected parameters, capsaicin-loaded PLGA nanoparticles were successfully produced. The particles were prepared using a microfluidic platform, and the organic phase was subsequently removed via solvent evaporation. The resulting formulations were comprehensively characterized in terms of particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency (%EE). Additionally, the in vitro release profiles and cytotoxicity of capsaicin-loaded nanoparticles were evaluated. This study aimed to elucidate the decisive role of surfactant parameters in the microfluidic production of PLGA nanoparticles and to contribute to the development of optimized and reproducible formulations. Full article

Background: Actinium-225 (²²⁵Ac) is receiving major attention as the radionuclide of choice for targeted alpha therapy (TAT) due to its outstanding physical properties such as a long physical half-life of 9.9 days and a short range of alpha (α)-particles which are responsible for the destruction of malignant tumors, whilst sparing normal surrounding tissues. Although the physical properties of ²²⁵Ac make it a desirable radionuclide for TAT, its application is challenging due to the lack of chelators available to stabilize its daughter radionuclides, resulting in the recoil effect. This occurs when there is a breakdown between the radionuclide and the chelator, therefore minimizing the therapeutic effects of the radiopharmaceutical. Nanodrug delivery systems (NDDSs) may minimize the challenge of ²²⁵Ac’s recoiling daughters and increase tumor penetration. Aim: This study aimed at using poly(lactic-co-glycolic)acid (PLGA) and chitosan (CS) nanoparticles as a delivery vehicle for targeted alpha therapy of prostate cancer in order to increase the therapeutic effect of ²²⁵Ac PSMA617-TFA. Methods and Results: PLGA nanoparticles were prepared using a nanoprecipitation method, after which they were functionalized with chitosan and folic acid. Following synthesis of ²²⁵Ac PSMA617-TFA, the radiopharmaceutical was loaded onto the nanoparticles. SEM analysis and FTIR were performed for characterization of the nanoparticles, and in-vitro drug release of ²²⁵Ac PSMA617-TFA at pH = 6.5 and pH = 7.4, respectively, was measured. The nanoparticles prepared had an average size of 200 nm and had a positive charge. This was further confirmed using a zetasizer and with scanning electron microscope (SEM) analysis. The PLGA-CS nanoparticles indicated a high encapsulation efficiency after 24 h. The results also showed a controlled release of ²²⁵Ac PSMA617-TFA over 72 h. The results of this study indicate that PLGA-CS nanoparticles are suitable for retaining ²²⁵Ac and its recoiling daughters (²²¹Fr and ²¹³Bi) at the tumor site, potentially providing a platform for future therapeutic evaluation. Conclusions: The results of this study indicate that PLGA-CS nanoparticles demonstrate feasibility as a drug delivery vehicle for ²²⁵Ac PSMA617-TFA, with effective retention of ²²⁵Ac and its decay daughters. However, biological validation through in vitro cellular studies and in vivo preclinical models is required before therapeutic effectiveness can be established. Full article

In this study, novel electrospun polymer mats based on biocompatible poly(lactic acid) (PLA) and hydrophilic poly(ethylene glycol) (PEG) were successfully fabricated for the co-delivery of two natural polyphenols, quercetin (QUE) and rosmarinic acid (RA). Scanning electron microscopy (SEM) revealed the formation of defect-free, continuous nanofibers with high interconnected porosity. By mimicking the structural features of the native extracellular matrix, these nanofibrous platforms facilitate pronounced combined antioxidant and anticancer action. X-ray diffraction (XRD) analysis confirmed that the rapid solvent evaporation during electrospinning induced a physical state transformation, converting both QUE and RA from their native crystalline structures into an amorphous dispersion within the polymer fibrous materials, thereby optimizing their potential bioavailability. The obtained hybrid fibrous materials possessed good mechanical properties. Moreover, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay demonstrated that the incorporation of PEG enhanced matrix hydrophilicity, allowing the four-component PLA/PEG/QUE/RA mats to achieve the highest antioxidant efficiency (98.1%), suggesting an enhanced, complementary radical-neutralization pathway. Furthermore, in vitro biological assessments against human cervical carcinoma cell line (HeLa) and normal murine embryo fibroblasts BALB/3T3 demonstrated prominent anticancer activity, while noncancerous cells were significantly less affected. The dual-loaded PLA/PEG/QUE/RA fibrous mats induced significant cell shrinkage, chromatin condensation, and apoptotic cell death in HeLa cells, while normal BALB/3T3 fibroblasts retained cell membrane integrity and displayed higher resistance. Modeled after the native extracellular matrix, these bioinspired materials demonstrate significant antioxidant and anticancer activity, highlighting their potential for applications in localized cancer therapy, wound management, and tissue engineering. Full article

Background/Objectives: Poly(lactic-co-glycolic acid) (PLGA) microparticles are widely used for sustained drug delivery, yet the release behavior reported in the literature remains difficult to predict across studies. It was hypothesized that this limitation reflects insufficient information content in commonly reported formulation variables rather than model inadequacy. Methods: A curated dataset of 321 PLGA microparticle formulations from 113 publications comprising 89 drugs and 4913 release observations was analyzed. Early time release was parameterized using Korsmeyer–Peppas descriptors (n, K), and burst release was quantified as the 24 h cumulative release. Machine learning models were evaluated using formulation-grouped cross-validation, applicability-domain analysis, and leave-one-study-out validation to assess cross-laboratory transportability. Results: Under formulation-grouped validation, predictability was limited (stacked ensemble: $R^2=0.156$ for n, $R^2=0.169$ for K, burst $R^2=0.100$). Leave-one-study-out validation yielded negative pooled $R^2$ values for all targets ($-0.061$, $-0.040$, and $-0.180$, respectively), indicating failure to generalize across laboratories. Applicability-domain filtering did not materially improve performance, supporting the interpretation that prediction is limited by missing or inconsistently reported variables rather than covariate extrapolation alone. Conclusions: These results reveal an information-limited regime in PLGA release prediction in which the literature covariates enable only weak formulation-level prediction under grouped validation and cannot support transferable models. Minimum reporting priorities are therefore proposed, including standardized characterization of polymer molecular weight, end-group chemistry, quantitative emulsification and solvent-removal parameters, and microstructural or porosity measurements, to enable reproducible formulation screening. Full article

Colorectal cancer (CRC) is driven by oxidative stress, chronic inflammation, and disruption of cytoprotective signaling pathways. This study aimed to evaluate whether poly(lactic-co-glycolic acid) (PLGA)-based nanoparticle delivery enhances the chemoprotective efficacy of paeonol against 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis, with a focus on modulation of the NRF2/HO-1 pathway. Sixty male Wistar rats were randomly assigned to six groups: control, paeonol (PNL), PNL-PLGA, DMH, DMH + PNL, and DMH + PNL-PLGA. CRC was induced using DMH over 10 weeks. Serum tumor biomarkers (AFP, CEA, CA19-9, CA125, CA15-3), oxidative stress markers (ROS, MDA, antioxidant enzymes), inflammatory cytokines, DNA damage, apoptosis- and autophagy-related gene expression, and hepatic and renal function were assessed. Histopathological and ultrastructural analyses of colonic tissues were performed. DMH exposure was markedly associated with increased tumor biomarkers, oxidative stress, and inflammatory mediators, DNA damage, and impaired liver and kidney function. It was also associated with the restoration of NRF2/HO-1 signaling, improved redox balance, suppression of inflammation, reduction in DNA damage, and preservation of regulated NRF2/HO-1 signaling, antioxidant defenses, autophagy markers, and apoptotic proteins, as well as severe histological and ultrastructural alterations. Free paeonol partially attenuated these changes. In contrast, PNL-PLGA was significantly associated with restoring NRF2/HO-1 signaling, improving redox balance, suppressing inflammation, reducing DNA damage, and preserving colonic architecture and ultrastructure. These findings demonstrate that a PLGA-based nanoformulation of paeonol markedly improves its chemopreventive efficacy against DMH-induced CRC, primarily by activating NRF2/HO-1 signaling and modulating oxidative stress, inflammation, apoptosis, and autophagy, highlighting its potential as a promising nanotherapeutic strategy for colorectal cancer. Full article

Additive manufacturing has emerged as a transformative technology for fabricating complex drug-eluting medical devices, offering unprecedented design freedom and functional integration capabilities. This comprehensive review systematically analyzes 3D printing technologies applied to pharmaceutical device manufacturing, focusing on drug-eluting vascular stents as a representative application. This review covers six primary additive manufacturing techniques, ranging from high-resolution vat photopolymerization (25 μm resolution) to direct energy deposition, with a focus on their capabilities for produce pharmaceutical devices with controlled drug release properties. Novel 4D/5D/6D printing technologies introduce stimuli-responsive behaviors enabling programmable drug release profiles and adaptive device functionality. Manufacturing process optimization reveals superior design flexibility compared to conventional methods, with 85–95% reduction in design iteration time and elimination of tooling costs for complex geometries. The material landscape encompasses traditional metals (316L stainless steel, cobalt–chromium), biodegradable polymers (polylactic acid, PLA; polycaprolactone, PCL; poly(lactic-co-glycolic acid), PLGA), shape-memory materials (i.e., polymers and alloys capable of recovering a pre-programmed shape upon exposure to a specific stimulus such as body temperature, moisture, or light), and advanced nanocomposites, each offering distinct drug-loading capacities (100–500 μg/cm²) and release kinetics. Critical challenges include standardization requirements (International Organization for Standardization (ISO) 5840 and American Society for Testing and Materials (ASTM) F2606), pharmaceutical-grade manufacturing protocols, and regulatory pathways for novel drug-device combinations. This review identifies key research priorities including development of biocompatible printing materials, accelerated drug release testing protocols, and scalable manufacturing processes suitable for medical device production. This analysis demonstrates that 3D printing enables integration of multiple pharmaceutical functions within single devices, controlled spatiotemporal drug delivery, and elimination of secondary manufacturing steps for drug coating processes, advancing the development of next-generation therapeutic medical devices. Full article

Hepatocellular carcinoma (HCC) is among the most prevalent and lethal malignancies worldwide, with limited therapeutic outcomes due to systemic toxicity and suboptimal efficacy of conventional chemotherapeutics such as doxorubicin (DOX). In this study, we formulated and standardized DOX-loaded chitosan/poly (lactic-co-glycolic acid) nanoparticles (DLCNs) via a nanoprecipitation method and evaluated their therapeutic potential in a diethylnitrosamine (DEN)-induced Wistar rat model of HCC. Physicochemical analyses confirmed nanoscale size, favorable zeta potential, and high encapsulation efficiency, while Fourier-transform infrared spectroscopy (FTIR) verified polymer–drug interactions. Biochemical analysis revealed that DLCNs significantly normalized elevated liver function markers (Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), restored serum α-fetoprotein (AFP) to near-control levels, and reduced lipid peroxidation compared with free DOX and DEN controls. Antioxidant profiling demonstrated marked recovery of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), indicating restoration of hepatic redox balance. Histopathological evaluation further corroborated these findings, showing recovery of hepatic lobular architecture and reduction in necrosis and inflammatory infiltrates in DLCN-treated Wistar Albino rats, while free DOX groups exhibited hepatocellular damage. Overall, the results demonstrate that encapsulating DOX in a chitosan/PLGA nanocarrier improves therapeutic efficacy, mitigates hepatotoxicity, and enhances antioxidant defense, establishing DLCNs as a favorable candidate for HCC. Full article

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation and chronic airway inflammation. Current therapeutic strategies primarily offer symptomatic relief and are often limited by systemic side effects, inadequate lung deposition, and poor patient compliance. Naringin (NAR), a natural flavonoid with strong antioxidant, anti-inflammatory, and anti-fibrotic activities, has demonstrated potential in mitigating COPD-associated pathophysiology. However, its therapeutic application is restricted by poor water solubility, low bioavailability, and rapid metabolism. Nanotechnology-based drug delivery systems, particularly poly(lactic-co-glycolic acid) (PLGA) nanoparticles, provide an effective approach for lung-targeted therapy. Their nanoscale size promotes deep lung deposition, enhanced cellular uptake, reduced lung clearance, improved therapeutic efficacy, and reduced systemic side effects. The present study aimed to develop NAR-loaded PLGA nanoparticles (NAR PLGA NP) for enhanced cell-targeting in inflammatory lung conditions. NAR PLGA NP were prepared using the emulsion solvent evaporation method, with PLGA in the organic phase and soya lecithin (SL) with poly(vinyl alcohol) (PVA) as surfactants in the aqueous phase. A face-centered central composite design was employed to optimize the formulation. The optimized nanoparticles were characterized for size distribution by dynamic light scattering, entrapment efficiency, Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), and in vitro drug release. The safety of PLGA and lecithin-coated PLGA nanoparticles (LC PLGA NP) was assessed using an MTT assay on lung epithelial cells, followed by cellular uptake studies, angiogenesis by chick Yolk Sac Membrane (YSM) assay, and in vitro evaluation of reactive oxidative stress (ROS) and anti-inflammatory activity. The optimized PLGA formulation showed a hydrodynamic diameter of 201 ± 1 nm with PDI 0.20 ± 0.03 and EE of 76.11 ± 2.1%, and 81.7 ± 4.9% drug release at 72 h, whereas LC PLGA NP showed a hydrodynamic diameter of 308 ± 3 nm, PDI of 0.21 ± 0.05, entrapment efficiency of 82.45 ± 4.8%, and 71.4 ± 3.2% drug release at 72 h. Both PLGA NP and LC PLGA NP demonstrated good cytocompatibility with lung epithelial cells, efficient cellular uptake, and a significant reduction in intracellular reactive oxygen species (ROS) levels (**** p value < 0.0001). Moreover, the formulations markedly suppressed pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, indicating anti-inflammatory activity. The angiogenesis assay further suggested their ability for lung tissue repair and remodeling. These findings support the potential of LC PLGA NP as a promising cell-specific targeting system for naringin in inflammatory lung conditions. Full article

Background/Objectives: Flavonoids are low-molecular-weight polyphenolic compounds that are universally distributed in plants. They are a chemically varied group of secondary metabolites with a broad range of biological activity. The use of flavonoids is known to decrease the risk of many chronic diseases due to their radical scavenging, antioxidant, anti-inflammatory, anticarcinogenic, and antimutagenic properties. Limitations in the use of flavonoids include their low water solubility and poor stability, and therefore their low bioavailability. The encapsulation of flavonoids in different nanocarriers has helped to overcome this limitation. Taking this into account, in this work, the encapsulation of four flavones with several therapeutic applications—7-hydroxyflavone, 7,8-dihydroxyflavone, baicalein, and luteolin—in poly(lactic-co-glycolic) acid (PLGA)-derived polymeric nanoparticles (NPs) has been investigated. Methods: A physicochemical characterization of the NPs has been carried out using different techniques, including the evaluation of antioxidant and antimicrobial activities. Results: In all cases, the encapsulation efficiency of the four flavones in the prepared NPs was high (>90%), the zeta potential was about −31 mV, and the size was nanometric (~450 nm). The drug release from the nanoparticles was also studied, showing first-order kinetics. Statistical tools were applied to the release rate constants. The antioxidant activity and the in vitro antimicrobial activity of the free and flavone-loaded NPs were investigated, in the case of the latter using Gram-positive and Gram-negative bacteria. Results show that when the flavones are encapsulated, they retain their therapeutic properties. Conclusions: In summary, PLGA-based NPs not only prevent flavone degradation but also significantly boost solubility, ultimately optimizing bioavailability. Our results underscore these NPs as a promising platform for efficient flavone delivery. Full article

Autoimmune diseases are characterized by chronic inflammation, immune dysregulation, and excessive oxidative stress, which collectively contribute to a progressive tissue damage and organ dysfunction. Although conventional immunosuppressive and anti-inflammatory therapies remain the main therapeutic approach, their clinical efficacy is often limited by poor pharmacokinetic properties, low tissue selectivity, systemic toxicity, and adverse effects following long-term administration. In this context, antioxidant-based nanoformulations have emerged as promising multi-target therapeutic strategies for the modulation of oxidative and inflammatory pathways involved in autoimmune disorders. This review focuses on polymeric and non-polymeric nanoformulations designed to improve the solubility, stability, bioavailability, controlled release, and targeted delivery of antioxidant and anti-inflammatory agents for autoimmune disease treatment. Recent advances in nanocarrier systems applications, including nanogels, poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), polymethacrylate, chitosan, hyaluronic acid, hydroxyapatite (HAP), lipid-based and ROS-responsive nanosystems, are discussed. The therapeutic potential of nanoencapsulated steroidal and non-steroidal anti-inflammatory drugs, antioxidant compounds, enzymes, inorganic elements, and nucleic acid-binding systems is evaluated through preclinical and limited clinical evidence. Many of these reported nanoformulations exhibit enhanced therapeutic efficacy, improved tissue targeting, reduced systemic toxicity, and the ability to simultaneously modulate oxidative stress and inflammatory signaling pathways. Despite the encouraging findings, important challenges remain regarding clinical translation, long-term safety, reproducibility, and large-scale production. In overall, antioxidant nanoformulations represent a promising and evolving platform for the development of more effective and targeted therapies against autoimmune diseases. Full article

Solid tumors typically expand in a “cold” immunosuppressive tumor microenvironment (TME) and resist killing by CAR T cells or conventional therapy. Herein, we show that intratumoral injection of C3a and C5a receptor 1 (C3ar/C5ar1) pharmaceutical antagonists in an in situ forming implant (ISFI) can robustly suppress such tumors. Antagonizing autocrine C3ar/C5ar1 signaling in eight human and murine cancers of diverse lineages was universally anti-mitotic and pro-apoptotic in vitro, and growth-repressive in vivo. In contrast to i.p. administration of C3ar/C5ar1 antagonists to tumor-bearing mice, injecting the antagonists intratumorally in slow release poly (lactic-co-glycolic acid) (PLGA) polymer caused near-complete tumor elimination. The focused blockade of C3ar/C5ar1 GPCR signaling in an intratumoral ISFI opposed solid cancers by jointly repressing cancer cell viability/growth, tumor-associated angiogenesis, and myeloid-derived suppressor cell (MDSC) recruitment. Thus, the sustained blockade of C3ar/C5ar1 signaling in an intratumoral ISFI uninterruptedly disrupts three processes essential for solid cancer growth while avoiding adverse effects on other cell types. Our findings may apply to multiple cancer types in which discrete tumor masses can be targeted. Full article

Anterior cruciate ligament reconstruction relies on interference screw fixation, yet insufficient graft osseointegration remains a critical clinical challenge. This study aimed to develop and characterize a 3D-printed polymeric–hydroxyapatite composite interference screw with an osteoinductive surface to enhance localized osteogenic responses. Screws were designed, modeled, and fabricated using fused deposition modeling 3D printing with a polycaprolactone-poly(lactic-co-glycolic acid)-hydroxyapatite composite. Physico-chemical characterization was performed using scanning electron microscopy. Biocompatibility was assessed through mesenchymal stem cell metabolic activity assays and morphological analysis. Osteogenic gene expression was quantified by RT-qPCR following culture in osteogenic differentiation medium. In vivo osseointegration was evaluated histologically at five and nine weeks following implantation in the proximal tibial epiphysis of a rat model. 3D printing successfully produced screws with consistent geometry and surface characteristics. The composite material supported robust mesenchymal stem cell proliferation without cytotoxicity or morphological abnormalities. Histological examination revealed progressive bone formation with no adverse tissue reactions, including the absence of cyst formation, osteolysis, or excessive fibrosis. RT-qPCR revealed upregulation of osteogenic markers in those enhanced screws. These results indicate that the 3D-printed polymeric–hydroxyapatite composite screws are biocompatible and capable of stimulating localized osteogenic activity, supporting their potential as a biological foundation for future evaluation in anterior cruciate ligament reconstruction applications. Full article