
Cancer therapies are often limited by poor cellular specificity and tumor microenvironment-mediated immunosuppression. We developed a dual-function graphene oxide (GO)-based gene delivery platform combining direct cancer cell elimination with stromal and immune reprogramming. CD47-targeting siRNA and ANT1-encoding plasmid DNA selectively induced apoptosis in tumor cells, while TGFβ-targeting siRNA altered cancer-associated fibroblasts (CAFs) phenotype and was associated with a shift in macrophage polarization toward a pro-inflammatory, tumor-restraining phenotype. We evaluated this approach in a 3D multicellular lung cancer model consisting of A549 cells, human lung fibroblasts, and THP1-derived macrophages. TGFβ silencing alone modulated stromal and immune features without direct cytotoxicity, whereas CD47/ANT1 modulation reduced overall cell viability to ∼51%. When both therapeutic functions were applied together, overall cell viability was further reduced to ∼29%. EGFR-targeted GO-CD47-ANT1 (GE11-peptide modified formulation) enhanced tumor-cell uptake and selective apoptosis in CK7+ cancer cells to 91%, while sparing CK7- nonmalignant populations (16%). Mechanistically, combined therapy suppressed immunosuppressive macrophage markers (CD163, IL10, TGFβ), restored epithelial integrity (E-cadherin 3.5-fold), and attenuated CAF activation (αSMA 0.3-fold; vimentin 0.6-fold). GE11 peptide functionalization shifted nanocarrier internalization toward EGFR-mediated cancer cell uptake, minimizing off-target delivery to fibroblasts and macrophages. These findings demonstrate that synergistic modulation of cancer cells and the tumor microenvironment is essential for robust and selective tumor elimination. Our study establishes a modular, mechanism-informed GO platform integrating dual therapeutic functions-targeted cancer cell killing and microenvironmental reprogramming-highlighting its translational potential in physiologically relevant tumor models.
This in vitro study was designed to assess and compare the color stability of pigmented maxillofacial silicone elastomers reinforced with nano-zirconia and nano-zinc oxide with silicone without nanoparticles following accelerated weathering at various time intervals. A total of 150 disc-shaped pigmented maxillofacial silicone specimens were prepared and classified into one control group of 50 silicone elastomers pigmented without nanoparticles and two experimental groups of 50 nano-zirconia (ZrO2) and 50 nano-zinc oxide (ZnO). The samples were then exposed to artificial weathering for 200, 400, and 600 h of accelerated weathering. All color measurements were performed at baseline and after aging using same specimens assigned to each interval with a spectrophotometer in the Commission Internationale de l'Eclairage (CIELAB) color space. Color differences (ΔE) were analyzed using two-way repeated measures ANOVA with Greenhouse-Geisser correction (p < 0.05). Color change values of both groups increased markedly with time aging, indicating that nanoparticle reinforcement significantly influenced the color change over time. At all aging intervals, the ZrO2 group demonstrated the lowest ΔE values, followed by ZnO, while the control group exhibited the highest discoloration. After 600 h of accelerated aging, mean ΔE values were 3.23 for the control group, 2.82 for ZnO, and 2.16 for ZrO2, exhibiting a superior color stability of zirconia-reinforced silicone. Nano-ZrO2 showed better color change stability than nano-ZnO at all aging periods, indicating that it may be used to increase the esthetic longevity of maxillofacial silicone prosthesis.
Background:Bone defects caused by trauma, congenital disorders and degenerative diseases such as osteoporosis remain a major clinical challenge, especially in developing regions. Although bone grafting is the current gold standard for treating bone defects, it faces limitations, including donor site morbidity, limited availability and immune rejection. This study developed and evaluated a novel hybrid biomaterial composed of bovine β-lactoglobulin fibrils (BLGFs), oxidized dextran (ODEX) and collagen (COL) extracted from Chambo tilapia fish skin for bone tissue engineering applications. Methods:BLGFs were synthesized from whey protein, while ODEX was produced by oxidizing dextran. Three biomaterials-COL, BLGFs/ODEX and BLGFs/ODEX/COL-were synthesized and characterized using Fourier-transformed infrared (FTIR), scanning electron microscope (SEM), and X-ray diffraction (XRD). Cytocompatibility and haemocompatibility were assessed through MTT and haemolysis assays using rat red blood cells. Osteogenic potential was evaluated by Alizarin Red staining after culturing rat bone marrow stem cells in osteoinduction media. Results:The BLGFs/ODEX/COL hydrogel exhibited better porosity, biocompatibility and mechanical stability. SEM and MTT results confirmed robust cell adhesion, spreading, and viability, while haemolysis rates remained below 5%. Enhanced calcium deposition in rBMSCs indicated strong osteogenic differentiation. These results demonstrate that the BLGFs/ODEX/COL hydrogel is a promising, affordable, and biocompatible scaffold for bone tissue regeneration.
Tissue engineering aims to repair, replace, or regenerate damaged tissues by integrating principles of biology, engineering, and material science. Traditional ex vivo strategies, involving prefabricated cell/scaffold constructs followed by implantation, have shown promise but face significant limitations, including poor vascularization, immune rejection, high costs, and clinical translation challenges. These limitations have driven the emergence of in situ tissue engineering, which harnesses the body’s intrinsic regenerative capacity by recruiting endogenous stem or progenitor cells to sites of injury for repair. A key requirement for successful in situ regeneration is the design of biomimetic three-dimensional scaffolds capable of delivering bioactive molecules such as growth factors and cytokines in a controlled and spatiotemporal manner. In addition to biochemical cues, mechanobiology plays a central role by regulating cell adhesion, migration, proliferation, and differentiation through mechanotransduction pathways involving cytoskeletal remodeling, extracellular matrix (ECM) dynamics, and nuclear signaling. This review highlights mechanobiology-mediated strategies, scaffold designs, and applications for hard and soft tissue repair, as well as challenges and future directions in regenerative medicine.
Rapid technological advancement has led to a growing need for new materials with enhanced properties to meet the demands of emerging applications. Traditional single-component materials often fail to meet the required demands, pushing the exploration of new composite materials. In these contexts, polyhedral oligomeric silsesquioxanes (POSS) as hybrid nanomaterials exhibit excellent mechanical, thermal and chemical stability, making them ideal for advanced material design. In addition, their hydrophobic nature and ability to be functionalized enable antimicrobial properties with enhanced resistance to microbial adhesion. Compared to hybrid nanomaterials, single-component antiviral materials have limitations, including short-term durability and low surface stability. The rationale for developing the POSS-stearic acid hybrid composite is based on the ability to form a rigid nanocage framework of POSS, which provides structural robustness and enhanced stability. We show that by combining POSS with stearic acid, the hybrid material displays greater hydrophobicity than its individual components, making it an effective surface coating material that prevents the attachment of microbial pathogens, including viruses, such as human coronavirus-OC43 (HCoV-OC43) and Type A influenza virus (H1N1). We provide evidence that the present material not only serves as a barrier to viral attachment to the surface but also significantly reduces viral infectivity, possibly through direct neutralization, thereby offering a promising strategy for mitigating surface-mediated transmission of respiratory viruses.
Titanium implants can release ions that damage cells. Anodization creates a protective oxide layer, but conventional acid methods raise environmental and safety concerns. This study evaluates in vitro cytotoxicity and osseointegration with the Psidium guajava aqueous leaf extract (PgE) as an alternative anodization electrolyte for titanium plates. For this purpose, 1-cm2 titanium plates were anodized with H3PO4, a combination of H3PO4+HF or PgE, and each group was assessed for its impact on cell viability, adhesion, and proliferation in osteosarcoma (Saos-2) and fibroblast (NIH-3T3) cells. The plate surfaces were characterized by energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (PXRD), and contact angle measurements using the sessile drop method, demonstrating greater hydrophilicity in plates anodized with PgE. Cytotoxicity was assessed using both indirect assays (extraction media) and direct assays, where cells were seeded directly onto titanium plates; cell viability was determined by MTT and NRU assays after 24 and 96 h. Osseointegration was analyzed by counting nuclei through DAPI staining and adhesion using scanning electron microscopy. In indirect assays, all samples showed no significant difference compared to the control (ANOVA/Tukey’s; p < 0.05), while direct assays demonstrated an average increase in cell viability on all anodized plates. The number of cell nuclei increased on H3PO4 and PgE plates in both cell lines compared to pure titanium. SEM analysis revealed improved cell morphology and adhesion on surfaces anodized with H3PO4 or PgE, whereas cells on H3PO4+HF appeared thinner and less spread, suggesting impaired cellular anchorage. The results show that using PgE as an anodization electrolyte for titanium plates caused no cytotoxicity and enhanced cell proliferation and adhesion, outperforming conventional H3PO4+HF electrolyte. This makes it a promising and sustainable alternative aligned with green chemistry principles.
Cytotoxicity testing is a critical step in the preclinical evaluation of biomaterials and medical devices, with extracellular matrix (ECM)-based biomaterials constituting a significant category. The current ISO 10993-5:2009 standard, Biological Evaluation of Medical Devices-Part 5: Tests for In Vitro Cytotoxicity, delineates four metabolic assays that primarily rely on colorimetric methods and colony formation. However, relying solely on colorimetric assays or colony formation fails to provide precise insights into cell function/activity and may yield false-positive results, contributing to interlaboratory discrepancies. This study systematically evaluated ISO 10993-5-recommended assays for ECM-based commercial products, specifically assessing the impact of key assay variables including cell types, contact mode (test extracts versus test material itself), and media components (with or without serum) on biological outcomes. These evaluations support the development of more accurate and robust test methods. While all four assays indicated the noncytotoxic nature of the test samples, metabolic activity readings varied substantially depending on the serum presence, cell types, and assay method employed. To address these limitations and achieve more precise insights into cellular activity, cell membrane integrity (live/dead staining), cell-ECM attachment (actin cytoskeleton), proliferation (Ki67), and apoptosis (annexin V) were analyzed. Notably, despite observing increased metabolic activity (100%-150%) under serum-free conditions measured using MTT and XTT assays, live/dead and actin staining showed no corresponding changes in cell viability or attachment, and Ki67 indicated only ∼15% proliferation. Annexin V staining was detected only in human primary dermal fibroblasts, highlighting their greater reliability over L929 cells for detecting apoptosis. These findings provide a valuable reference for researchers, regulatory bodies, and industry stakeholders in refining cytotoxicity testing protocols and guiding future ISO 10993-5 revisions for more reliable assessment of biomaterials and medical devices.
Aim:Modification of conventional glass ionomer cement (GIC) using nanofillers is a promising approach to enhance its clinical performance. This study aimed to evaluate the surface roughness and color stability of conventional GIC after modification with a synthesized 70:30 hydroxyapatite/chitosan (HA/CTS) nanocomposite. Materials and Methods:A 70:30 hydroxyapatite/chitosan nanocomposite was synthesized and incorporated into GIC powder at 1, 3, and 5 wt.%. Four groups were prepared: Group I (control), Group II (1 wt.% HA/CTS), Group III (3 wt.% HA/CTS), and Group IV (5 wt.% HA/CTS). A total of 80 specimens were fabricated (n = 10 per group for each test). Surface roughness (Ra) was measured using a profilometer, while color stability (ΔE) was assessed using a spectrophotometer. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test (α = 0.05). Results:GIC modified with the 3 wt.% HA/CTS nanocomposite exhibited the lowest surface roughness and demonstrated clinically acceptable color change (ΔE ≤ 3.3) (p < 0.05). Higher nanocomposite loading (5 wt.%) resulted in significantly increased surface roughness and clinically perceptible color alteration. Conclusions:Incorporation of the 3 wt.% 70:30 HA/CTS nanocomposite into conventional GIC produced a smoother surface and acceptable esthetic outcome, suggesting a promising formulation for improved clinical performance.
BackgroundThe involvement of human subjects in the development of biomedical devices presents both ethical and practical challenges. Electroencephalography (EEG) signals exhibit interindividual variability and are subject to fluctuations induced by movement and emotional states. Hence, the fabrication of artificial tissues (phantoms) capable of accurately replicating human organs and tissues is of critical importance. The primary objective of this study was to create phantoms that accurately mimic the electrical conductivity of human head tissues.MethodsPhantom compositions were optimized to accomplish these objectives. This article details the fabrication and characterization of 116 tissue-mimicking rat head size phantoms (RHSPs) with diverse concentrations, mixing durations, volumes, and combinations of gelatin, salt, reduced graphene oxide (rGO) solution, silver nanopowder (Ag), graphite powder (Gr), polyvinyl alcohol (PVA) solution, sodium alginate (SA) solution, PVA/SA solutions, and potassium sorbate (KS), evaluated for their electrical conductivity properties using an LCR meter. Using the electrical conductivity values derived from the RHSP data, a regression equation was developed in Python, which was then employed to fabricate a human head phantom (HHP).ResultsConductive polymer-based phantoms with electrical conductivity and biological properties comparable to real cranial tissues were successfully developed, making them suitable for EEG electrode and cap applications. The developed HHP was powered by a signal generator, and artificial EEG brain waves were generated using the OpenBCI platform. Based on the acquired data, brain simulations were conducted using the low-resolution electromagnetic tomography (LORETA) program. The trials produced phantoms with electrical conductivity consistent with that of most tissues within the layers of the human skull. The study provides a framework for the economical and efficient fabrication of both single- and multilayer head phantoms.
The fabrication of novel bioelectrodes using electrospun nanofibers and a prototype for a sustainable triboelectric nanogenerator (TENG) is explored in this study. Poly(lactic acid-caprolactone) (PLCL) was electrospun as the matrix of the bioelectrode and functionalized with a commercial graphene XT3. Afterward, the fibers were coated with graphene ink (Gr.ink) or poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS). The average diameter of nanofibers increased multifold after coating. PEDOT:PSS-coated fibers showed the highest Young's modulus at 98 MPa. The nanofiber mats did not show decreased metabolic activity below the cytotoxic threshold. Graphene-functionalized PLCL fiber coated with Gr.ink showed a significant decrease in proliferation compared to untreated cells. The tested mats did not support human dermal cells' adhesion. The nanofibers blended with graphene and coated with PEDOT:PSS showed the highest conductivity, sufficient for use in TENG devices. A TENG device was assembled using PEDOT:PSS-covered PLCL/graphene fiber mats as electrodes and poly(lactic acid) with poly(glycerol sebacate) as active contact layers. The TENG device achieved a power density of 1.9 mW m-2 and, during 1 min of operation, charged the capacitor to a voltage corresponding to 71 nJ of stored energy. The TENG module proposed could address the energy demands of healthcare monitoring and wearable electronics, sustainably.
Infections, limited biocompatibility, and material degradation remain major challenges for metallic implants in biomedical applications. To address these issues, this study presents a multifunctional coating strategy for Grade 2 titanium using a base layer of segmented polyurethane (Tecoflex SG-80A), followed by the co-deposition of titanium dioxide nanoparticles and gentamicin sulfate. Corrosion polarization tests revealed enhanced passivation of polyurethane-coated surfaces with no signs of pitting corrosion. Coatings showed porous microstructures with both nanoparticles and antibiotics distributed within and along pore edges. Energy-dispersive X-ray spectroscopy (EDX) confirmed the surface presence of both components. Thermogravimetric analysis indicated loadings of 0.17 ± 0.02 mg of gentamicin and 0.30 ± 0.04 mg of TiO2 per specimen. SEM and AFM analyses showed that over 86% of the surface was covered with gentamicin and nanoparticles. Contact angle measurements revealed a hydrophilic character (35°) for coatings containing both gentamicin and TiO2 nanoparticles, favorable for biological interactions. Cytotoxicity assays using dental pulp mesenchymal cells and fibroblasts demonstrated no cytotoxic effects after 72 h, whereas antibacterial tests against Staphylococcus aureus and Escherichia coli indicated inhibitory effects. Gentamicin release from the coatings followed the Korsmeyer-Peppas model, suggesting a diffusion-driven profile. These results support the development of durable, biocompatible, and antibacterial coatings for titanium implants that can reduce infection risk, enhance corrosion resistance, and support tissue integration.
3D printing has emerged as an innovative technology over the last decade, with widespread uptake in several fields spanning science, technology and engineering; however, penetration into medical markets has been met with a variety of obstacles. At the 17th Global Conference on Sustainable Manufacturing in 2018, medical technology stakeholders held a workshop to discuss the barriers that hinder the widespread adoption and diffusion of 3D printing technology in the Australian medical field. Patient-specific 3D-printed bone scaffolds were the central focus of this workshop, with five major barriers identified: material issues; manufacturing and postprocess approval; medical and professional endorsement and adoption; reimbursement; and staff training. To determine the progress made towards overcoming these barriers, we have reviewed the body of literature published from the 2018 conference until now. The most significant progress was observed in material issues with a significant increase in the number of materials and combination of materials that have been successfully printed and used in multiple animal trials and limited human cases. Manufacturing and postprocess approval issues that enable 3D-printed bone scaffold implantation have seen preliminary success with a handful of case trials documented with various levels of success, yet a distinct level of development is still required to satisfy this barrier before commercial production parameters and widespread adoption will be recognized. Medical and professional endorsement and adoption, reimbursement and staff training are yet to experience significant progression, with the possibility that the extent of these barriers will not be clearly understood until well after regulatory approval has been achieved.
Microneedle-based access to plant phloem enables sustainable energy harvesting and in situ biochemical sensing, but its performance is limited by defense responses such as callose deposition triggered by mechanical overstimulation of cell walls. This study presents a combined numerical-experimental framework for investigation how microneedle penetration dynamics influence transient stress fields within plant cellular tissue. A 3D finite element model of tomato stem tissue was reconstructed from SEM data, incorporating elastic-plastic cell walls, compressible intracellular fluid, and an augmented-Lagrangian contact to simulate cell-wall rupture and middle-lamella delamination. Simulations reveal that lower insertion velocities significantly reduce stress transients and localize stress propagation, favoring single-cell failure over multicell delamination. This effect results from a reduced rate of energy transfer into the tissue during insertion, limiting elastic energy accumulation and mechanical loading of mechanosensory pathways associated with callose secretion. Microneedle prototypes were fabricated and tested on tomato stems. Despite the quasistatic experimental velocities, displacement-based comparison showed good agreement with numerical predictions. Both approaches confirmed that slower penetration shifts energy partitioning toward elastic storage and rheological dissipation. Overall, the developed mesoscale FEM framework reliably captures microneedle-tissue interactions and provides a transferable tool for optimizing minimally disruptive microneedle insertion strategies.
Background:Eugenol is a phenolic compound known for its antimicrobial, antifungal, and antioxidant properties. Its encapsulation in chitosan nanoparticles (EuChiNPs) enhances stability and therapeutic efficacy. Objectives:This study aimed to investigate the effects of EuChiNPs on Helicobacter pylori (H. pylori) infection in rats, focusing on its impact on inflammatory and apoptotic pathways. Methods:EuChiNPs were synthesized and characterized using DLS, TEM, and FTIR techniques. A total of 42 male Wistar rats were divided into six groups, including controls, H. pylori-infected, and treatment groups receiving EuChiNPs, standard antibiotics, or a combination. The effects of treatments were evaluated using RT-PCR, ELISA, Western blotting, and histopathology. Results:The combination of EuChiNPs and standard antibiotics significantly reduced the expression of inflammatory markers interleukin-1 beta (IL-1β) and interleukin-8 (IL-8). Serum levels of IL-1β, IL-8, and TNF-α were markedly decreased in the combination group compared with antibiotics alone (p < 0.0001). Western blot analysis revealed a reduction in caspase-3 and caspase-7 expression, indicating attenuation of apoptosis. Histopathological analysis showed improved mucosal integrity and reduced bacterial density in the combination treatment group. Conclusion:EuChiNPs demonstrated strong anti-inflammatory and antiapoptotic effects, especially when combined with standard antibiotics. This novel approach promises to improve H. pylori eradication while minimizing antibiotic resistance and side effects. Further clinical studies are recommended to validate these findings.
Collagen is the most abundant structural protein in animals and a key biomaterial due to its biocompatibility, biodegradability, and versatile functional properties. Traditionally, collagen has been obtained from land animal tissues such as bovine, porcine, and donkey skin, tendon, and bone. However, concerns regarding disease transmission, immunogenicity, and cultural restrictions have driven the exploration of alternative sources. Marine organisms, including fish, jellyfish, and sea cucumber, provide collagens that are widely reported to exhibit lower immunogenic responses compared with mammalian sources, alongside reduced zoonotic and prion-related safety concerns, although these observations are context-dependent and influenced by species origin, processing methods, and intended application. More recently, recombinant technologies using microbial and eukaryotic expression systems have emerged as innovative strategies to produce human-like collagens with tailored properties and improved safety. Together, these diverse sources expand the availability of collagen for a wide range of applications, from food and beverage systems to biomedical uses in tissue engineering, wound healing, and cosmetics. By outlining the advantages and limitations of land animal, marine, and recombinant collagen sources, this review highlights the growing importance of collagen as a multifunctional biomaterial and underscores the potential of emerging sustainable alternatives.
The incorporation of bio-based additives into polymers offers potential sustainability benefits, providing a more environmentally friendly alternative for applications in bioplastics and composites. However, the comparative effects of microalgae or Spirulina in polypropylene (PP) versus ethylene vinyl acetate (EVA) at fixed loadings without compatibilizers remain largely unknown. This study evaluates the influence of incorporating the biomass Arthrospira platensis (Spirulina) on the properties of two different polymer matrices: PP and EVA. The composites were prepared using an internal mixer as a torque rheometer, followed by compression molding to produce test specimens. Morphological and dispersion analyses were conducted using scanning electron microscopy (SEM) and optical microscopy. Mechanical properties were assessed through bending tests (ASTM D790) and toughness tests (ASTM D5045), and thermal characterization was performed using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). In the EVA, poor adhesion was observed between the Spirulina biomass and the polymer matrix, resulting in modest reductions in stiffness without significant compromise of the mechanical properties compared to the neat polymer, suggesting that Spirulina may act primarily as a filler. In the PP, better dispersion and adhesion of the biomass to the polymer matrix were observed. A 53% reduction in elasticity (Young’s modulus) was observed; however, no rupture occurred in the specimens containing Spirulina during the toughness tests, indicating its effectiveness in enhancing the toughness of the matrix, highlighting the feasibility of using its biomass as an additive in polymer matrices, with implications for the development of sustainable materials.
Green chemistry has recently made strides in the sustainable synthesis of next-generation nanomaterials using reducing agents sourced from plants. Biocompatible conversion of reduced graphene oxide from graphene oxide nanomaterials is of particular interest in medical applications. The leaf extract of C. igneus functions as a reducing agent to produce reduced graphene oxide nanosheets from its precursor graphene oxide. A variety of characterization techniques were employed to confirm the formation and stability of reduced graphene oxide nanosheets. The cytotoxicity and glucose uptake potential of nanosheets have been evaluated through in vitro cell-based assays. The MTT assay revealed a concentration-dependent cytotoxic effect on Chang liver and U87MG cells, with maximum 84.5% and 76.3% cell viability, respectively. Reduced graphene oxide exhibited a significant rise in glucose uptake, comparable to the metformin drug, with increasing concentration. Enhanced glucose transport mediated by the nanosheets resulted in increased glucose uptake. Effective IC50 values of 84.46 μg·mL-1 and 93.83 μg·mL-1 were obtained in vitro enzyme inhibition studies against α-amylase and α-glucosidase, respectively. The enzyme kinetic investigation found noncompetitive inhibition for both enzymes. Molecular docking studies of C. igneus leaf derivatives were performed against α-amylase and α-glucosidase. Corosolic acid was selected based on favorable docking scores, binding interactions, and low root-mean-square deviation and was subjected to molecular dynamics simulations, which confirmed the stability of the resulting complex. This study concludes that reduced graphene oxide nanosheets derived from C. igneus leaves represent a novel antidiabetic agent that can reduce blood glucose levels and mitigate the complications associated with Type II diabetes.
Cellulose-based hydrogel films are promising alternatives to plastic for wrapping. Hydrogel films based on carboxymethyl cellulose (CMC) and microcrystalline cellulose (MCC) must exhibit high mechanical strength and be capable of absorbing moisture. Crosslinking increases the absorption capacity and mechanical strength of hydrogel films. As a filler, MCC can synergize with citric acid, which acts as an environmentally friendly crosslinker to enhance mechanical strength. This research aimed to develop a suitable CMC/MCC formulation and citric acid as a crosslinker, resulting in a hydrogel with high water absorption and mechanical strength. CMC/MCC formulations were combined with citric acid concentrations of 5%, 7.5%, and 10%. The results showed that the MCC and citric acid will affect absorption and mechanical strength. The addition of MCC up to 50% tends to produce a brittle hydrogel film, and this phenomenon is also correlated with increased citric acid. A 90:10 CMC/MCC formulation with 5% citric acid (w/v) resulted in a water uptake of 222.72 ± 9.32 at pH 7.0. In contrast, the 80:20 CMC/MCC formulation resulted in a water uptake of 603.02 ± 26.98. They both showed higher rehydration of the dry gel than the others. FTIR confirmed the sharpening of the peak wave number at 1705 cm-1, which is identical to the protonated carbonyl group and correlates with the water absorption capacity. The morphology of hydrogel films containing a CMC/MCC ratio of 90:10 exhibits a smoother surface than that of those with a CMC/MCC ratio of 80:20, which feature bubbles on the surface cracks of the hydrogel film due to the presence of more water absorption channels. Hydrogel films with a CMC/MCC ratio of 90:10 and 5% citric acid (w/v) can be developed for wrapping by modifying their hygroscopic properties. In contrast, hydrogel films with an 80:20 ratio and 5% citric acid are suitable for use as absorbents.
Gelatin-based nanoformulations have received special attention for drug delivery applications because of their regulatory acceptability. A thorough understanding of the factors controlling the interaction of gelatin nanocarriers with cellular systems is crucial for their future biomedical applications. The present study addresses the effect of genipin crosslinking on the ability of gelatin nanoparticles (GNPs) to deliver curcumin, a pharmacologically active ingredient from turmeric into lung cancer (A549) cells. Briefly, the methodology was optimized to prepare GNP (15 mg/mL) crosslinked with 0.25, 0.5, and 1.0 mg/mL of genipin (GN-GNP1-3, respectively). The crosslinking of GN-GNP1-3 was established through UV-VIS, Fourier transform infrared spectroscopy, and circular dichroism measurements. Dynamic light scattering and transmission electron microscopy showed nearly identical hydrodynamic size (165 ± 15 nm) and shape (spherical) for GN-GNP1-3. Subsequently, these nanocarriers were loaded with curcumin and evaluated for drug delivery properties (loading efficiency and release kinetics), cellular uptake, cytotoxicity, and associated mechanisms. These studies together revealed that GN-GNP1-3 of increasing degree of crosslinking exhibited higher curcumin loading efficiency, facilitated slow and sustained release of curcumin over a prolonged period (80 h) by a non-Fickian mechanism, and ultimately increased the cellular uptake and the effectiveness (or cytotoxicity) of entrapped curcumin in A549 cells. The pharmacological abrogation investigations established that curcumin-loaded GN-GNP3 was internalized within A549 cells through caveolae-mediated endocytosis. In conclusion, genipin crosslinking of gelatin-based nanocarriers seemed to be a novel strategy to increase the cellular uptake cum effectiveness of a hydrophobic payload like curcumin.
Background:Microbes having affinity to metallic surfaces develop a highly structured and sessile colony known as biofilms which poses significant challenges to the domain of implant surgery. Biofilm-mediated infections and the associated burden have prompted the search for multipronged approaches to tackle the problem. Gram-positive pathogens, most notably Staphylococcus aureus, has been known to colonize human tracts and form biofilms on implants and prosthetic devices. Antibiotic tolerance, drug efflux, and recalcitrance to the host immune response have added to the existing predicament of the biofilm infections. Objective:The search for inexpensive but effective avenues for combating biofilms has led to the use of metal nanoparticles conjugated with plant-derived proteins. Methods:In this study, a protein from Moringa oleifera leaf extract, p62, which has been previously identified to have antibiofilm properties, was conjugated with spherical gold nanoparticles (AuNPs) to target S. aureus biofilm formation. Results:The adsorption of p62 on the AuNPs was confirmed through microscopy, and the kinetics of binding was determined by plasmon resonance. The p62 coated AuNPs remained stable in solution and caused the successful disintegration of mature biofilms, more efficiently than the protein alone. The p62-AuNPs were also found to disrupt the morphology of the cocci and cause cell death as evidenced from the live/dead cell imaging through confocal microscopy. The protein and the nanoparticle were not cytotoxic to C2C12 human myoblast cell lines, affirming their suitability to be used on implants.