Search Results (140)

According to the World Health Organization, musculoskeletal injuries affect more than 1.71 billion people around the world. These injuries are a major public health issue and the leading cause of disability. There has been a recent interest in hydrogels as a potential biomaterial for musculoskeletal tissue regeneration. This is due to their high water content (70–99%), ECM-like structure, injectability, and controllable degradation rates. Recent preclinical studies indicate that they can enhance regeneration by modulating the release of bioactive compounds, growth factors, and stem cells. Composite hydrogels that combine natural and synthetic polymers, like chitosan and collagen, have compressive moduli that are advantageous for tendon–bone healing. Some of these hydrogels can even hold up to 0.8 MPa of tensile strength. In osteoarthritis models, functionalized systems such as microspheres responsive to matrix metalloproteinase-13 have demonstrated disease modulation and targeted drug delivery, while intelligent in situ hydrogels have exhibited a 43% increase in neovascularization and a 50% enhancement in myotube production. Hydrogel-based therapies have been shown to restore contractile force by as much as 80%, increase myofiber density by 65%, and boost ALP activity in bone defects by 2.1 times in volumetric muscle loss (VML) models. Adding TGF-β3 or MSCs to hydrogel systems improved GAG content by about 60%, collagen II expression by 35–50%, and O’Driscoll scores by 35–50% in cartilage regeneration. Full article

In recent years, significant progress has been made in breast reconstructive surgery, particularly with the use of three-dimensional (3D) disassemblable scaffolds. Reconstructive plastic surgery aimed at restoring the shape and size of the mammary gland offers medical, psychological, and social benefits. Using autologous tissues allows surgeons to recreate the appearance of the mammary gland and achieve tactile sensations similar to those of a healthy organ while minimizing the risks associated with implants; 3D disassemblable scaffolds are a promising solution that overcomes the limitations of traditional methods. These constructs offer the potential for patient-specific anatomical adaptation and can provide both temporary and long-term structural support for regenerating tissues. One of the most promising approaches in post-mastectomy breast reconstruction involves the use of autologous cellular and tissue components integrated into either synthetic scaffolds—such as polylactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), and polycaprolactone (PCL)—or naturally derived biopolymer-based matrices, including alginate, chitosan, hyaluronic acid derivatives, collagen, fibrin, gelatin, and silk fibroin. In this context, two complementary research directions are gaining increasing significance: (1) the development of novel hybrid biomaterials that combine the favorable characteristics of both synthetic and natural polymers while maintaining biocompatibility and biodegradability; and (2) the advancement of three-dimensional bioprinting technologies for the fabrication of patient-specific scaffolds capable of incorporating cellular therapies. Such therapies typically involve mesenchymal stromal cells (MSCs) and bioactive signaling molecules, such as growth factors, aimed at promoting angiogenesis, cellular proliferation, and lineage-specific differentiation. In our review, we analyze existing developments in this area and discuss the advantages and disadvantages of 3D disassemblable scaffolds for mammary gland reconstruction, as well as prospects for their further research and clinical use. Full article

Glioblastoma is the most common and aggressive malignant primary brain tumour. Patients with glioblastoma have a median survival of only around 14.6 months after diagnosis, despite the availability of various conventional multimodal treatments including chemotherapy, radiation therapy, and surgery. Therefore, photodynamic therapy (PDT) has emerged as an advanced, selective and more controlled therapeutic approach, which has minimal systemic toxicity and fewer side effects. PDT is a less invasive therapy that targets all cells or tissues that possess the photosensitizer (PS) itself, without affecting the surrounding healthy tissues. Polymeric NPs (PNPs) as carriers can improve the targeting ability and stability of PSs and co-deliver various anticancer agents to achieve combined cancer therapy. Because of their versatile tuneable features, these PNPs have the capacity to open tight junctions of the blood–brain barrier (BBB), easily transport drugs across the BBB, protect against enzymatic degradation, prolong the systemic circulation, and sustainably release the drug. Conjugated polymer NPs, poly(lactic-co-glycolic acid)-based NPs, lipid–polymer hybrid NPs, and polyethylene-glycolated PNPs have demonstrated great potential in PDT owing to their unique biocompatibility and optical properties. Although the combination of PDT and PNPs has great potential and can provide several benefits over conventional cancer therapies, there are several limitations that are hindering its translation into clinical use. This review aims to summarize the recent advances in the combined use of PNPs and PDT in the case of glioblastoma treatment. By evaluating various types of PDT and PNPs, this review emphasizes how these innovative approaches can play an important role in overcoming glioblastoma-associated critical challenges, including BBB and tumour heterogeneity. Furthermore, this review also discusses the challenges and future directions for PNPs and PDT, which provides insight into the potential solutions to various problems that are hindering their clinical translation in glioblastoma treatment. Full article

Background/Objectives: Personalized 3D-printed (3DP) metallic implants delivery systems are being explored to repair bone fractures, allowing the customization of medical implants that respond to individual patient needs, making it potentially more effective and of greater quality than mass-produced devices. However, challenges associated with postsurgical infections caused by bacterial adhesion remain a clinical issue. To address this, local antibiotic therapies are receiving extensive attention to minimize the risk of implant-related infections. This study investigated the use of amikacin (AMK), a broad-spectrum aminoglycoside antibiotic, incorporated onto 3D-printed 316L stainless steel implants using biodegradable polymer coatings of chitosan and poly lactic-co-glycolic acid (PLGA). Methods: This research examined different approaches to coat 3DP implants with amikacin. Various polymer-based coatings were studied to determine the optimal formulation based on the characteristics and release profile. The optimal formulation was performed on the antibacterial activity studies. Results: AMK-chitosan with PLGA coating implants controlled the rate of drug release for up to one month. The 3DP drug-loaded substrates demonstrated effective, concentration-dependent antibacterial activity against common infective pathogens. AMK-loaded substrates showed antimicrobial effectiveness for one week and inhibited bacteria significantly compared to the uncoated controls. Conclusions: This study demonstrated that 3DP metal surfaces coated with amikacin can provide customizable drug release profiles while effectively inhibiting bacterial growth. These findings highlight the potential of combining 3D printing with localized delivery strategies to prevent implant-associated infections and advance the development of personalized therapies. Full article

Human adipose stem cells (ASCs) are multipotent cells expressing mesenchymal stem cell (MSC) markers that are capable of multilineage differentiation and secretion of bioactive factors. Their “homing” to injured tissues is mediated by chemokines, cytokines, adhesion molecules, and signaling pathways. Enhancing ASC homing is critical for improving regenerative therapies. Strategies include boosting chemotactic signaling, modulating immune responses to create a supportive environment, preconditioning ASCs with hypoxia or mechanical stimuli, co-culturing with supportive cells, applying surface modifications or genetic engineering, and using biomaterials to promote ASC recruitment, retention, and integration at injury sites. Scaffolds provide structural support and a biomimetic environment for ASC-based tissue regeneration. Natural scaffolds promote adhesion and differentiation but have mechanical limitations, while synthetic scaffolds offer tunable properties and controlled degradation. Functionalization with bioactive molecules improves the regenerative outcomes of different tissue types. Ceramic-based scaffolds, due to their strength and bioactivity, are ideal for bone healing. Composite scaffolds, combining polymers, ceramics, or metals, further optimize mechanical and biological properties, supporting personalized regenerative therapies. This review integrates concepts from cell biology, biomaterials science, and regenerative medicine to offer a comprehensive understanding of ASC homing and its impact on tissue engineering and clinical applications. Full article

Antimicrobial resistance arises from treatment non-adherence and ineffective delivery systems. Optimal wound dressings combine localized drug release, exudate management, and bacterial encapsulation through hydrogel-forming nanofibers for enhanced therapy. In this work, polylactic acid (PLA) and polyvinylpyrrolidone (PVP) fibers loaded with chlorhexidine (CHX) were developed using Solution Blow Spinning (SBS), a scalable electrospinning alternative that enables in situ deposition. Molecular interactions between CHX and polymers in solution (by UV-Vis and fluorescence spectroscopy) and in solid state (by FTIR, XRD and thermal analysis) were studied. The morphology of the polymeric fibers was determined by optical microscopy, showing that PVP fibers are thinner (1625 nm) and more uniform than those of PLA (2237 nm). Finally, drug release from single-polymer fibers discs, overlapping fibers discs (PLA/PVP/PLA and PVP/PLA/PVP), and solid dispersions was determined by UV-Vis spectrometry. PVP-based fibers exhibited faster CHX release due to their hydrophilic nature, while PLA fibers proved sustained release, attributed to their hydrophobic matrix. This study highlights the potential of PLA/PVP-CHX fibers made from SBS as advanced wound dressings, combining biocompatibility and personalized drug delivery, offering a promising platform for localized and controlled antibiotic delivery. Full article

Graphene-based materials (GBMs) have shown significant promise in cancer therapy due to their unique physicochemical properties, biocompatibility, and ease of functionalization. Their ability to target solid tumors, penetrate the tumor microenvironment (TME), and act as efficient drug delivery platforms highlights their potential in nanomedicine. However, the complex and dynamic nature of the TME, characterized by metabolic heterogeneity, immune suppression, and drug resistance, poses significant challenges to effective cancer treatment. GBMs offer innovative solutions by enhancing tumor targeting, facilitating deep tissue penetration, and modulating metabolic pathways that contribute to tumor progression and immune evasion. Their functionalization with targeting ligands and biocompatible polymers improves their biosafety and specificity, while their ability to modulate immune cell interactions within the TME presents new opportunities for immunotherapy. Given the role of metabolic reprogramming in tumor survival and resistance, GBMs could be further exploited in metabolism-targeted therapies by disrupting glycolysis, mitochondrial respiration, and lipid metabolism to counteract the immunosuppressive effects of the TME. This review focuses on discussing research studies that design GBM nanocomposites with enhanced biodegradability, minimized toxicity, and improved efficacy in delivering therapeutic agents with the intention to reprogram the TME for effective anticancer therapy. Additionally, exploring the potential of GBM nanocomposites in combination with immunotherapies and metabolism-targeted treatments could lead to more effective and personalized cancer therapies. By addressing these challenges, GBMs could play a pivotal role in overcoming current limitations in cancer treatment and advancing precision oncology. Full article

Malignant skin conditions are classified as the most common forms of cancer, with an evolution of one million new cases reported every year. Research efforts in the medical field are focused on developing innovative strategies for the dissemination of measures for preventing cancer and providing new antitumor compounds. The present research examines the development and evaluation of 1% Carbopol-based hydrogels incorporating two porphyrin derivatives—5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1) and 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2)—to create formulations suitable for topical photodynamic therapy (PDT) applications. The physicochemical properties of the obtained hydrogels were carefully evaluated, revealing the successful integration of the porphyrins into the 1% Carbopol hydrogel matrix. Rheological analysis demonstrated pseudoplastic behavior, with an increase in viscosity properties for P2.1 and P2.2, suggesting interactions with the Carbopol polymer structure. UV-visible and fluorescence spectroscopy confirmed the maintenance of the porphyrins’ photodynamic properties, essential for therapeutic efficacy. Pharmacotechnical studies highlighted the hydrogels’ suitability for topical applications. The formulations maintained an optimal pH range, ensuring skin compatibility and minimizing the potential for skin irritation. Their mechanical properties, including elasticity and rigidity, provided stability during handling and application. The high swelling capacity indicated effective moisture retention, enhancing skin hydration and drug release potential. Furthermore, the hydrogels demonstrated excellent spreadability, enabling uniform application and coverage, crucial for efficient light activation of the photosensitizers. The combination of robust physicochemical and pharmacotechnical properties highlights the potential of these porphyrin-loaded 1% Carbopol hydrogels as promising carriers for topical PDT. These results permit further biological and therapeutic investigations to optimize the formulation for clinical use, advancing the development of effective localized photodynamic therapies. Full article

Efficient and precise cancer therapy remains a challenge due to limitations in current treatment modalities. In this study, we developed a multifunctional hydrogel system that integrates photothermal therapy (PTT) and chemotherapy to achieve combined tumor treatment. The hydrogel, composed of γ-polyglutamic acid (γ-PGA), fifth-generation polyamide-amine dendrimers (G5), and polydopamine (PDA) nanoparticles, exhibits high photothermal conversion efficiency and temperature-responsive drug release properties. The hydrogel exhibited a high photothermal conversion efficiency of 45.6% under 808 nm near-infrared (NIR) irradiation. Drug release studies demonstrated a cumulative hydrophilic anticancer drug doxorubicin DOX release of 79.27% within 72 h under mild hyperthermia conditions (50 °C). In vivo experiments revealed a significant tumor inhibition rate of 82.3% with minimal systemic toxicity. Comprehensive in vitro and in vivo evaluations reveal that the hydrogel demonstrates excellent biocompatibility, photothermal stability, and biodegradability. Unlike conventional hydrogel systems, our γ-PGA-based hydrogel uniquely integrates a biocompatible and biodegradable polymer with polydopamine (PDA) nanoparticles, providing a smart and responsive platform for precise cancer therapy. This multifunctional hydrogel system represents a promising platform that combines PTT precision and chemotherapy efficacy, providing a robust strategy for advanced and safer cancer treatment. Full article

The printing of composite magnetic filaments using additive manufacturing techniques has emerged as a promising approach for biomedical applications, particularly in bone tissue engineering and magnetic hyperthermia treatments. This study focuses on the synthesis of nanocomposite ferromagnetic filaments and the fabrication of bone tissue scaffolds with time-dependent properties. Three classes of polylactic acid-based biocompatible polymers—EasyFil, Tough and Premium—were combined with magnetite nanoparticles (Fe₃O₄) at concentrations of 10 wt% and 20 wt%. Extruded filaments were evaluated for microstructural integrity, printed dog-bone-shaped specimens were tested for elongation and mechanical properties, and cylindrical scaffolds were analyzed for magnetic hyperthermia performance. The tensile strength of EasyFil polylactic acid decreased from 1834 MPa (0 wt% Fe₃O₄) to 1130 MPa (−38%) at 20 wt% Fe₃O₄, while Premium polylactic acid showed a more moderate reduction from 1800 MPa to 1567 MPa (−13%). The elongation at break was reduced across all samples, with the highest decrease observed in EasyFil polylactic acid (from 42% to 26%, −38%). Magnetic hyperthermia performance, measured by the specific absorption rate, demonstrated that the 20 wt% Fe₃O₄ scaffolds achieved specific absorption rate values of 2–7.5 W/g, depending on polymer type. Our results show that by carefully selecting the right thermoplastic material, we can balance both mechanical integrity and thermal efficiency. Among the tested materials, Tough polylactic acid composites demonstrated the most promising potential for magnetic hyperthermia applications, providing optimal heating performance without significantly compromising scaffold strength. These findings offer critical insights into designing magnetic scaffolds optimized for tissue regeneration and hyperthermia-based therapies. Full article

Polymer-based drug-controlled release systems offer greater efficacy and potency than conventional therapies. However, prominent drug side effects, lower circulation, and low drug loading capabilities limit their application range. In this work, the combination of Simvastatin (SIV) and Carvacrol (CAV) into PEG-PLGA microspheres (SIV-CAV-PP-MS) was achieved via an emulsification-solvent evaporation technique, resulting in microspheres characterized by high encapsulation efficiency and reduced particle size. In vitro studies demonstrated that the cumulative drug release increased with higher SIV and CAV levels in the release medium, reaching 88.91% and 89.35% at 25 days. Pharmacokinetic analysis revealed that the concentrations of SIV and CAV reached their maximum levels at approximately seven days in the SIV-CAV-PP-MS group, which indicates that using PEG-PLGA as a carrier significantly delays drug release. In vivo, evaluation demonstrated that the SIV-CAV-PP-MS high-dose group and positive drug control group showed reductions in low-density lipoprotein cholesterol levels by 0.39-fold and 0.36-fold compared to the Hyperlipidemia model group, and the addition of CAV significantly enhanced the lipid-lowering effects of SIV. Histological examinations indicated that the SIV-CAV-PP-MS medium-dose group displayed histological features more closely resembling those of normal mice compared to the Simvastatin control group, with a well-organized hepatocyte structure, a significant reduction in lipids, and improved liver health. The prepared polymeric microsphere utilizing SIV and SAV will be a promising dosage form for hyperlipidemia disease patients, with superior lipid-lowering efficacy and improved patient compliance. Full article

Localization in the central nervous system, diffuse growth, the presence of stem cells, and numerous resistance mechanisms, all make glioblastoma (GBM) an incurable tumor. The standard treatment of GBM consisting of surgery; radio- and chemotherapy with temozolomide provides insufficient therapeutic benefit and needs to be updated with effective modern solutions. One of the most promising and intensively explored therapeutic approaches against GBM is the use of nanotherapy. The first, and so far only, nanoparticle-based therapy approved for GBM treatment is NanoTherm^TM. It is based on iron oxide nanoparticles and the thermal ablation of the tumor with a magnetic field. Numerous other types of nanotherapies are being evaluated, including polymer and lipid-based nanoformulations, nanodiscs, dendrimers, and metallic, silica, or bioderived nanoparticles, among others. The advantages of these nanoscale drug carriers include improved penetration across the blood–brain barrier, targeted drug delivery, biocompatibility, and lower systemic toxicity, while major problems with their implementation involve scaling up their production and high costs. Nevertheless, taking all the impressive benefits of nanotherapies into consideration, it seems obvious that the combined effort of the scientific world will need to be taken to tackle these challenges and implement these novel therapies into clinics, giving hope that the battle against GBM can finally be won. Full article

Photodynamic therapy (PDT) is a light-activated chemical reaction used for the selective destruction of tissue. For this, various colorants may be applied, such as erythrosine (ERI), a dye already approved by the Food and Drug Administration (FDA) for various purposes. Although promising for PDT, ERI has a high hydrophilic profile that impacts its activity. To solve this, the combination of ERI with thermoresponsive and bioadhesive polymers may prove effective. Bio/mucoadhesive and thermoresponsive systems have attracted increasing interest in the development of novel pharmaceutical formulations for topical applications due to their ability to improve adhesion to the mucosa and prolong the residence time at the application site. In this study, systems based on poloxamer 407 (P407) in combination with cellulose derivatives (HPMC and NaCMC) were optimized, aiming at the topical release of ERI for PDT. The results demonstrated that the formulations containing low concentrations of cellulose derivatives exhibited greater adhesiveness and consistency at physiological temperature (37 °C), favoring the maintenance of the system at the application site. Regarding the gelation temperature (T_sol/gel), the formulations displayed values close to body temperature. The formulations with NaCMC showed a slightly higher T_sol/gel compared to HPMC ones, but it was adjustable by the polymer concentration. The addition of ERI influenced the mechanical and adhesive properties of the systems. In formulations containing HPMC, high concentrations of ERI increased bio/mucoadhesiveness, while in systems with NaCMC, the presence of ERI reduced this property. In both cases, the formulations maintained high consistency at 37 °C, contributing to the control of the active release at the application site. Rheological analysis revealed non-Newtonian behavior in all formulations, with greater consistency and elasticity at high temperatures. P407 was mainly responsible for the thermoresponsive transition from sol to gel, conferring desirable characteristics for topical application. Photodynamic activity was relevant in both formulations containing NaCMC and HPMC, which demonstrated greater capacity for degrading uric acid under light exposure. These systems are promising for the controlled release of drugs in photodynamic therapy, providing prolonged retention in the target tissue and maximizing the therapeutic efficacy of ERI. Full article

Spinal cord trauma leads to the destruction of the highly organized cytoarchitecture that carries information along the axis of the spinal column. Currently, there are no clinically accepted strategies that can help regenerate severed axons after spinal cord injury (SCI). Hydrogels are soft biomaterials with high water content that are widely used as scaffolds to interface with the central nervous system (CNS). Here, we examine a simple and reproducible method that results in consistently aligned fibrils within 3D matrices using thermally gelling biomimetic polymers. A collagen type I (Col)-based thermally gelling hydrogel system was used in combination with two other native extracellular matrix proteins: laminin I (LN) and hyaluronic acid (HA). Gelling kinetics for all gel types (Col, Col LN, Col HA) showed that at 37 °C, all three hydrogels formed gels consistently. A method of aspiration and ejection was used to produce Col-based hydrogels containing aligned fibrils. In vitro, embryonic spinal cord neurons survived and produced processes aligned to collagen fibrils. Next, we implanted either non-aligned or aligned hydrogels after a bilateral dorsal hemisection of the thoracic spinal cord at T7/T8. Pan neuronal antibody-positive fibrils were found within all implants; aligned hydrogels supported neurite growth along the parallel direction of the implanted hydrogels. Combined, our in vitro and in vivo data indicate that thermally gelling biomimetic hydrogels can produce aligned matrices through a method of aspiration and ejection, and this presents a novel platform for regenerative therapies for the CNS. Full article

Cellulose acetate butyrate is a biodegradable cellulose ester bioplastic produced from plentiful natural plant-based resources. Solvent-exchange-induced in situ gels are particularly promising for periodontitis therapy, as this dosage form allows for the direct delivery of high concentrations of antimicrobial agents to the localized periodontal pocket. This study developed an in situ gel for periodontitis treatment, incorporating a combination of metronidazole and doxycycline hyclate, with cellulose acetate butyrate serving as the matrix-forming agent. Consequently, assessments were conducted on the physicochemical properties, gel formation, drug permeation, drug release, morphological topography, and antimicrobial activities of the formulation. The formulation demonstrated an increased slope characteristic of Newtonian flow at higher bioplastic concentrations. The adequate polymer concentration facilitated swift phase inversion, resulting in robust, solid-like matrices. The mechanical characteristics of the transformed in situ gel typically exhibit an upward trend as the polymer concentration increased. The utilization of sodium fluorescein and Nile red as fluorescent probes effectively tracked the interfacial solvent–aqueous movement during the phase inversion of in situ gels, confirming that the cellulose acetate butyrate matrix delayed the solvent exchange process. The initial burst release of metronidazole and doxycycline hyclate was minimized, achieving a sustained release profile over 7 days in in situ gels containing 25% and 40% cellulose acetate butyrate, primarily governed by a diffusion-controlled release mechanism. Metronidazole showed higher permeation through the porcine buccal membrane, while doxycycline hyclate exhibited greater tissue accumulation, both influenced by polymer concentration. The more highly concentrated polymeric in situ gel formed a uniformly porous structure. Metronidazole and doxycycline hyclate-loaded in situ gels showed synergistic antibacterial effects against S. aureus and P. gingivalis. Over time, the more highly concentrated polymeric in situ gel showed superior retention of antibacterial efficacy due to its denser cellulose acetate butyrate matrix, which modulated drug release and enhanced synergistic effects, making it a promising injectable treatment for periodontitis, particularly against P. gingivalis. Full article