The continuous advancement of tissue engineering demands the development of novel biomaterials and strategies to create functional and translational tissue constructs. Despite the emergence of new materials, gelatin remains one of the most practical and versatile, widely used biomaterials, combining biocompatibility, tunable properties, and ease of processing, while its biodegradability and derivation from circular economy resources further position it as a sustainable option. This review unfolds the recent trends in gelatin uses across three key areas. First, advances in functionalization, including chemical modifications that enhance mechanical properties and enable smart, self-healing systems, as well as hybridization with natural, synthetic, or inorganic components to expand multifunctionality. Second, innovations in fabrication techniques, from lyophilization and electrospinning to 3D and 4D bioprinting, which allow precise architectural control and patient-specific scaffold design. Third, emerging applications in tissue engineering, demonstrating the latest achievements of gelatin-based hydrogels, nanoparticles, and composites for skin, soft tissue, bone, cartilage, and ocular regeneration, including drug delivery and stimulus-responsive platforms. As predicted in previous reports on gelatin use, this versatile biomaterial continues to be one of the most widely applied and highly valued materials for tissue engineering purposes.

Cannabidiol (CBD) is a compound of high pharmacological interest, requiring accessible analytical methods for its identification and measurement. This study proposes the transformation of the classic Beam reaction, traditionally a qualitative colorimetric test, into a robust, low-cost quantitative technique using UV-Vis spectrophotometry. The method is based on the formation of a specific chromophore between CBD/CBDA and a 5

The phytochemical variability in Cannabis sativa L. chemovars represents an underexplored factor in environmentally sustainable nanomaterial production. In this study, three distinct chemovars, (i) High-Δ9-Tetrahydrocannabinol (THC) (89% THC), (ii) Balanced (60% Cannabidiol (CBD)), and (iii) High-CBD (89% CBD), were comparatively evaluated to determine their suitability for the green synthesis of silver nanoparticles (AgNPs). Ethanolic inflorescence extracts were used to recover bioactive secondary metabolites; among them, the High-CBD extract exhibited the highest total phenolic (3.34 mg gallic acid equivalent/g) and flavonoid (29.49 mg quercetine equivalent/g) contents, together with superior antioxidant capacity (53.16% 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH) inhibition), indicating enhanced redox potential for nanoparticle formation. The terpene profile of High-CBD showed a dominance of myrcene (21.4%), contributing to the stabilization of the system. Using the High-CBD extract, predominantly spherical nanoparticles of 5 ± 0.9 nm were synthesized and confirmed by UV-vis, EDS, and TEM. The biogenic AgNPs demonstrated significant dose-dependent antibacterial activity, with minimum bactericidal concentration (MBC) of 1.0 mg/mL against Staphylococcus aureus and 4.5 mg/mL against Escherichia coli. These findings highlight the critical role of chemovar-dependent phytochemical composition and support a phytochemistry-guided approach for developing silver nanoparticles with potential biomedical applications.

ABSTRACT The integration of nanomaterials into consumer products has outpaced our understanding of their immunological impact. This study evaluates the dose‐dependent effects of two commercial nanoparticle formulations, titanium dioxide (TiO 2 ) and silica (SiO 2 ), on RAW 264.7 murine macrophages. While both formulations possessed primary particle sizes of ∼24–27 nm, they differed in specific surface area, surface chemistry, and baseline aqueous dispersion behavior, with TiO 2 forming larger micron‐scale aggregates. FTIR confirmed characteristic Ti–O–Ti and Si–O–Si structural frameworks. Biological assays revealed contrasting cellular responses. The TiO 2 formulation exhibited substantially lower cytotoxicity than SiO 2 , maintaining viability while stimulating early metabolic activity (up to 130% of control at 24–48 h) and upregulating TNF‐α secretion by 50%–300%. Conversely, SiO 2 induced a potent, dose‐dependent reduction in metabolic activity, reaching an 85% decrease at higher concentrations (250–500 µg/mL) after 72 h. Normalizing nitric oxide secretion to total cellular metabolic activity revealed an activated, hyper‐secretory state in the remaining SiO 2 exposed population, despite reductions in uncorrected TNF‐α levels. These findings demonstrate that the distinct macrophage responses elicited by commercial TiO 2 and SiO 2 formulations are governed by an integrated ensemble of physicochemical properties, including surface area, surface chemical framework, and dispersion dynamics, rather than primary particle size or chemical identity alone.

Background/Objectives: Glaucoma is the leading cause of irreversible blindness worldwide and oxidative stress is considered to play a key role in its development. While antioxidants offer a promising approach to mitigating oxidative stress, their clinical application is often hindered by bioavailability and absorption challenges. Entrapment antioxidants within liposomes may overcome these issues, enhancing their stability and delivery. The aim of this study was to develop a novel composite liposomal formulation for glaucoma treatment, designed to enhance lipoic acid bioavailability and administration through its incorporation into the lipid bilayer. Methods: Liposomes were prepared via lipid film hydration and extrusion. To characterize them, the following analyses were performed: FTIR spectroscopy, liposomal bilayer melting temperature (Tm), TEM, DLS, Z-potential, antioxidant activity, and cytotoxicity assays. Results: The efficient incorporation of lipoic acid into the liposomes’ lipid bilayer was confirmed by FTIR. This incorporation resulted in an increase in the Tm, from 37.0 °C for liposomes to 40.0 °C for liposomes with lipoic acid (L-LA). TEM images confirmed that the spherical morphology of the lipid vesicles remained unchanged following LA incorporation. Dynamic Light Scattering analysis revealed effective diameters of 423 ± 36 nm for L liposomes and 404 ± 62 nm for L-LA liposomes. Notably, the Z-potential shifted from +4.7 ± 0.4 mV (L) to −0.4 ± 0.3 mV (L-LA). Furthermore, L-LA exhibited significant antioxidant activity (31.6 ± 0.4%) compared with L (5.3 ± 0.3%) and biocompatibility, suggesting its potential for therapeutic applications. Conclusions: In summary, biocompatible composite liposomes with antioxidant capacity were successfully developed, resulting in promising candidates for neuroprotective glaucoma therapy.

The search for biodegradable alternatives to traditional dressings has driven the development of thermoplastic starch nanocomposite films (T) with polyvinyl alcohol (P) and cellulose nanocrystals (CNC). Films were prepared via the casting technique with varying PVA concentrations (10, 20, 30, and 40 % w/v) and CNC reinforcements (2.5, 5.0, and 10 % w/w). The synthesis and characterization of copper oxide nanoparticles (NPCuO) was also carried out. The best-performing films were further modified with NPCuO to study their controlled release. The final material developed (T/P/10CNC/NPCuO) was extensively characterized, with measurements of thickness, swelling capacity in PBS buffer, tensile test, contact angle measurements, thermogravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FTIR). In addition, solubility, water vapor permeation, NPCuO release by visible ultraviolet spectroscopy (UV-Vis) and the cytocompatibility of the developed films were studied. NPCuO characterization showed hexagonal morphologies, a zeta potential of -32 mV, a hydrodynamic diameter of 122 nm (PDI = 0.5). Mechanical tests revealed that adding 10 % CNC tripled the stress at rupture compared to unreinforced films. Contact angle measurements (62°) confirmed hydrophilicity, a desirable property for dressings. The films showed good solubility in PBS, sustained release of nanoparticles for 8 h. Water vapor permeability increased from 0.9 to 1.75 g.mm-2.kPa-1.day-1 with CNC addition and to 1.88 g.mm-2.kPa-1.day-1 with NPCuO. NPCuO release was low but provided enhanced antioxidant activity: 76 % (24 h), 67 % (48 h), 43 % (72 h), and 38 % (96 h), outperforming T/P/10CNC. These nanocomposites exhibit promising mechanical, permeability, and antioxidant properties, making them suitable candidates for transdermal dressings.

Polycrystalline samples of Al 3+ -substituted barium–cobalt U-type hexagonal ferrites, with the chemical composition Ba 4 Co 2 Fe 36− x Al x O 60 ( x = 0.0, 0.2, 0.4, 0.6, 0.8 and 1.0), were synthesised.

Silica NPs (SiNPs) used as a platform to deliver molecules have huge potential for biomedical applications.

Cannabidiolic Acid (CBDA) is a promising natural compound with potent antioxidant, anti-inflammatory, and anti-emetic properties. Its antioxidant activity rivals that of vitamin E, while its anti-inflammatory effects are also remarkable. Additionally, CBDA has been shown to effectively reduce nausea and emetic attacks. As a more natural and water-soluble alternative to CBD, CBDA offers improved bioavailability and absorption. However, despite its promising potential, the development of effective CBDA delivery systems is still in its early stages. Among the various materials suitable for drug delivery, alginate is a widely used biopolymer due to its abundance and common availability in nature. This study aimed to develop an efficient CBDA delivery carrier using a microflow-dripping method to microencapsulate CBDA into alginate carriers (Alg-CBDA). The antioxidant, antimicrobial, and cytotoxicity properties of these Alg-CBDA capsules were then evaluated. Our results demonstrated that encapsulating CBDA within alginate capsules yielded a novel multifunctional biomaterial with prolonged antioxidant activity up to 72 h and antimicrobial activity against Gram-positive bacteria. Furthermore, the encapsulation process significantly reduced CBDA's cytotoxicity, broadening its potential applications. To our knowledge, this is the first study demonstrating the advantages of CBDA within a drug delivery framework.

UV-irradiation method has grown as an alternative approach to in situ synthetize silver nanoparticles (AgNPs) for avoiding the use of toxic reducing agents. In this work, an antimicrobial material by in situ synthesizing AgNPs within 3D-printed collagen-based scaffolds (Col-Ag) was developed. By modifying the concentration of AgNO3 (0.05 and 0.1 M) and UV irradiation time (2 h, 4 h, and 6 h), the morphology and size of the in situ prepared AgNPs could be controlled. As a result, star-like silver particles of around 23 ± 4 μm and spherical AgNPs of 220 ± 42 nm were obtained for Ag 0.05 M, while for Ag 0.1 M cubic particles from 0.3 to 1.0 μm and round silver precipitates of 3.0 ± 0.4 μm were formed in the surface of the scaffolds at different UV irradiation times. However, inside the material AgNPs of 10–28 nm were obtained. The DSC thermal analysis showed that a higher concentration of Ag stabilizes the 3D-printed collagen-based scaffolds, while a longer UV irradiation interval produces a decrease in the denaturation temperature of collagen. The enzymatic degradation assay also revealed that the in situ formed AgNPs act as stabilizing and reinforcement agent which also improve the swelling capacity of collagen-based material. Finally, antimicrobial activity of Col-Ag was studied, showing high bactericidal efficiency against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. These results showed that the UV irradiation method was really attractive to modulate the size and shape of in situ synthesized AgNPs to develop antimicrobial 3D-printed collagen scaffolds with different thermal, swelling and degradation properties.

Additive manufacturing, widely known as 3D printing, has revolutionized the production of biomaterials. While conventional 3D-printed structures are perceived as static, 4D printing introduces the ability to fabricate materials capable of self-transforming their configuration or function over time in response to external stimuli such as temperature, light, or electric field. This transformative technology has garnered significant attention in the field of biomedical engineering due to its potential to address limitations associated with traditional therapies. Here, we delve into an in-depth review of 4D-printing systems, exploring their diverse biomedical applications and meticulously evaluating their advantages and disadvantages. We emphasize the novelty of this review paper by highlighting the latest advancements and emerging trends in 4D-printing technology, particularly in the context of biomedical applications.

When silica nanoparticles (SiNP) reach the water bodies interact with the already existing pollutants in the environments. This study aimed to evaluate the ecotoxicity of SiNP under the presence/absence of Cu in mosquitofish (Gambusia holbrooki). Fish were exposed to 0, 10 and 100 mg SiNP L-1, alone or mixed with Cu (0.25 mg L-1). After 96 h, the amount of colony forming units (CFU) of bacteria living on the skin mucus was analysed, and oxidative stress, tissue damage enzymes, and neurotoxicity were evaluated. We observed a reduction in CFU when Cu was present in the media. The liver was the target organ, evidencing a decrease in tissue damage enzymatic activities, activation of the antioxidant system in all treatments, and lipid oxidative damage when the SiNP and Cu were mixed. Overall, SiNP ecotoxicity was proved, which could also be enhanced by the presence of ubiquitous elements such as metals.

Growth hormone deficiency has been treated by the daily administration of recombinant human growth hormone (hGH) for decades. Patient compliance to this treatment is generally incomplete due to challenges including dose frequency and lack of perceived benefits. This stimulates the research on new formulations to reduce the number of periodic administrations. In this study silica nanoparticles and silica-collagen nanocomposites were evaluated for hGH loading and release. Bare nanoparticles showed higher hGH adsorption capacity than thiol- and isobutyl-bearing particles of similar diameters. Monitoring of bound protein conformation changes indicated hGH structure retention when adsorbed on bare silica nanoparticles and suggested no alterations on protein activity. Protein-loaded particles incorporated into collagen matrices (silica-collagen nanocomposites) showed a progressive protein release profile different from the observed for hGH-loaded silica nanoparticles and hGH-loaded collagen matrices. While both the collagen and the silica nanoparticle systems reached a 100 % release after 4 and 7 days respectively, silica-collagen nanocomposites showed a bi-phasic prolonged hGH release reaching approximately an 80 % after 15 days. These findings suggest that biocompatible silica-collagen nanocomposites could be used as vehicles for the prolonged delivery of hGH which could lead to a potential reduction in the number of periodic administrations.

Silica nanoparticles (SiNP) are the most produced nanomaterials due to their variety of applications. When released to environments, surface water bodies are their main final sink. SiNP toxicity is still inconclusive and may vary according to particle properties such as their size. We analyzed the size-related effects of SiNP (22 and 244 nm) on mortality, life history traits, and oxidative stress in the cladoceran Ceriodaphnia reticulata. The smaller SiNP (LC5072 h: 105.5 µg/ml) were more lethal than the larger ones (LC5072 h >500 µg/ml). The 22 nm-sized SiNP decreased the number of molts and neonates, increased superoxide dismutase and inhibited glutathione S-transferase activities, while larger SiNP did not exert substantial effects on the organisms at the tested concentrations. In conclusion, SiNP toxicity depended on their size, and this information should be considered for regulatory purposes and to the development of safe-by-design nanoproducts to ultimately guarantee the environment protection.

Background: Green synthesis of nanomaterials has gained interest over the years as it has many benefits compared to conventional methods. Green methods are non-toxic and economic due to the use of aqueous extracts as reducing agents. Yerba mate is a widely used herb in South America, showing an available and economical alternative to conventional methods Methods: Different copper and zinc nanostructures were obtained using yerba mate extract (Ilex paraguariensis) as a reducing and capping agent. Furthermore, adjusting NaCl concentration and temperature, it was possible to successfully tune and examine the morphology of the resulting nanostructures by Scanning Electron Microscopy (SEM). Phenolic oxidation was evaluated by Raman spectroscopy and Fourier Transform Infrared Spectroscopy (FT-IR) to assess the role of yerba mate extract in the reaction. Moreover, antimicrobial activity versus Pseudomonas aeruginosa was assayed, and antioxidant activity was performed by the DPPH method. Results and Conclusion: The present study reveals a powerful method to obtain zinc and copper nanostructures, showing a logarithmic reduction of Pseudomonas aeruginosa of 2.14 and 5.92 CFU/mL at 96 hours respectively and scavenger activity of 42% and 22%, respectively. These properties highlight the potential of the nanomaterials for applications in catalysis, textile, biomedical and agricultural fields.

Synthetic and natural biomaterials are a promising alternative for the treatment of critical-sized bone defects. Several parameters such as their porosity, surface, and mechanical properties are extensively pointed out as key points to recapitulate the bone microenvironment. Many biomaterials with this pursuit are employed to provide a matrix, which can supply the specific environment and architecture for an adequate bone growth. Nevertheless, some queries remain unanswered. This review discusses the recent advances achieved by some synthetic and natural biomaterials to mimic the native structure of bone and the manufacturing technology applied to obtain biomaterial candidates. The focus of this review is placed in the recent advances in the development of biomaterial-based therapy for bone defects in different types of bone. In this context, this review gives an overview of the potentialities of synthetic and natural biomaterials: polyurethanes, polyesters, hyaluronic acid, collagen, titanium, and silica as successful candidates for the treatment of bone defects.

Electroactive hydrogels based on derivatives of polyethyleneglycol (PEG), chitosan and polypyrrole were prepared via a combination of photopolymerization and oxidative chemical polymerization, and optionally doped with anions (e.g., lignin, drugs, etc.). The products were analyzed with a variety of techniques, including: FT-IR, UV-Vis, 1H NMR (solution state), 13C NMR (solid state), XRD, TGA, SEM, swelling ratios and rheology. The conductive gels swell ca. 8 times less than the non-conductive gels due to the presence of the interpenetrating network (IPN) of polypyrrole and lignin. A rheological study showed that the non-conductive gels are soft (G′ 0.35 kPa, G″ 0.02 kPa) with properties analogous to brain tissue, whereas the conductive gels are significantly stronger (G′ 30 kPa, G″ 19 kPa) analogous to breast tissue due to the presence of the IPN of polypyrrole and lignin. The potential of these biomaterials to be used for biomedical applications was validated in vitro by cell culture studies (assessing adhesion and proliferation of fibroblasts) and drug delivery studies (electrochemically loading the FDA-approved chemotherapeutic pemetrexed and measuring passive and stimulated release); indeed, the application of electrical stimulus enhanced the release of PEM from gels by ca. 10–15% relative to the passive release control experiment for each application of electrical stimulation over a short period analogous to the duration of stimulation applied for electrochemotherapy. It is foreseeable that such materials could be integrated in electrochemotherapeutic medical devices, e.g., electrode arrays or plates currently used in the clinic.

There is an increasing medical need for the development of new materials that could replace damaged organs, improve healing of critical wounds or provide the environment required for the formation of a new healthy tissue. The three-dimensional (3D) printing approach has emerged to overcome several of the major deficiencies of tissue engineering. The use of Cannabis sativa as a therapy for some diseases has spread throughout the world thanks to its benefits for patients. In this work, we developed a bioink made with gelatin and alginate that was able to be printed using an extrusion 3D bioprinter. The scaffolds obtained were lyophilized, characterized and the swelling was assessed. In addition, the scaffolds were loaded with Cannabis sativa oil extract. The presence of the extract provided antimicrobial and antioxidant activity to the 3D scaffolds. Altogether, our results suggest that the new biocompatible material printed with 3D technology and with the addition of Cannabis sativa oil could become an attractive alternative to common treatments of soft-tissue infections and wound repair.