Achieving high shape fidelity remains a primary challenge in extrusion-based bioprinting, where the viscoelastic nature of hydrogels typically leads to "die swell", a post-extrusion expansion that compromises structural accuracy. This study presents a systematic investigation into the die swell phenomenon by analyzing the complex interplay between process parameters (pressure, temperature, nozzle diameter) and material rheology. Using a Design of Experiments (DOE) approach on functionalized collagen hydrogels, we isolated the main effects of process variables and identified significant interactions that modulate the swelling behavior. Crucially, by integrating rheological data, specifically the ratio between the first normal stress difference (N1) and shear stress (τ), with process kinematics, we developed a robust numerical model capable of predicting the extent of die swell. This model not only validates the theoretical framework of Tanner’s law in a bioprinting context but also provides a predictive tool for process optimization. These findings offer a foundational dataset and a mathematical framework that pave the way for future AI-driven strategies and machine learning algorithms aimed at real-time error correction in biofabrication.

Polymer matrix composites derived from organic waste represent a viable solution for enhancing environmental sustainability. This study investigates the development and characterization of eco-friendly composite filaments using polylactic acid (PLA) reinforced with orange peel particulates (OPPs), evaluating their potential for fused filament fabrication (FFF). PLA/OPP composites were fabricated with varying reinforcement concentrations (2.5-20 wt%) and different particle sizes. The materials were characterized through mechanical testing, thermal analysis (DSC), and FTIR spectroscopy, while functional performance was evaluated via DPPH and ABTS antioxidant assays. The experimental results indicated that a specific low OPP concentration (2.5 wt%) maintained the tensile strength of the neat matrix while significantly improving ductility by 16.67%, thereby enhancing the processability for fused deposition modeling (FDM). Conversely, reinforcement levels exceeding 10 wt% led to a decline in mechanical properties due to fiber agglomeration and matrix saturation. Thermal analysis revealed that higher OPP content influences the crystallization kinetics, while FTIR spectra confirmed good interfacial compatibility through hydrogen bonding. Notably, the incorporation of OPP imparted significant antioxidant activity to the composites, which increased proportionally with filler content. In conclusion, this study demonstrates that low-content PLA/OPP composites successfully balance mechanical performance with functional bioactivity, providing a sustainable material suitable for active packaging and 3D printing applications.

Poor solubility and low permeability remain major obstacles to the oral bioavailability of mesalazine (5-aminosalicylic acid, 5-ASA), a BCS Class IV anti-inflammatory drug used in the treatment of inflammatory bowel diseases. In this study, we report a novel eutectogel (EG) platform based on a natural deep eutectic solvent (NADES) composed of choline chloride and lactic acid (ChCl:LA, 1:10 molar ratio). The NADES significantly enhanced mesalazine solubility, reaching 35 mg/mL, nearly 40-fold higher than in water. The drug-loaded NADES was structured using hydroxyethyl cellulose and Carbomer 140 to obtain a gel matrix, which was subsequently coated with Eudragit (R) S100 to provide pH-dependent release and gastro-resistance. Physicochemical characterization was carried out via FT-IR and NMR spectroscopy, polarized optical microscopy (POM), and swelling studies in simulated fluids. In vitro release studies under simulated gastrointestinal conditions revealed minimal drug release at gastric pH (1.2) and a sustained release (>80%) at colonic pH (7.4) over 48 h. These results support the potential of ChCl:LA-based eutectogels as a biocompatible, green, and effective delivery system for the site-specific release of poorly soluble drugs in the colon.

Glioblastoma (GBM) is the most aggressive primary brain tumor and remains difficult to treat due to its invasive nature, therapeutic resistance, and the presence of the blood–brain barrier (BBB), which represents a major obstacle to effective drug delivery. This study describes the development of biocompatible solid lipid nanoparticles (SLNs) based on a novel arginine stearate derivative for the encapsulation of idebenone, a synthetic antioxidant with potential biological activity. The objective of this work was to design and characterize a lipid-based nanoparticulate system for idebenone delivery and to evaluate its physicochemical properties and preliminary in vitro biological effects. The nanoparticles were characterized by Dynamic Light Scattering (DLS) and Differential Scanning Calorimetry (DSC), and in vitro release profiles were investigated under different pH conditions. Antioxidant activity and cell viability assays were also performed in glioblastoma and non-tumorigenic cell lines. The results indicate successful formulation of idebenone-loaded SLNs with good encapsulation efficiency, maintained antioxidant activity, and promising physical stability over time as monitored by size analysis. The rationale behind the development of arginine stearate-based SLNSs is to optimize the performance of pharmaceutical active ingredients, such as idebenone, versus non-tumorigenic cells. Overall, these findings support the potential of the developed SLNs as a promising delivery system for further in vitro and in vivo investigations.

The effective management of perioperative and post-traumatic bleeding is critical to preventing severe complications, shock, and fatal outcomes. In this context, chitosan emerges as a premier polymeric biomaterial due to its exceptional biochemical properties and inherent hemostatic nature. Among commercially available solutions, the Axiostat sponge stands out as a promising device for promoting hemostasis at surgical and endovascular access sites. This study aimed to conduct a comprehensive chemical-physical characterization of the Axiostat device. The investigation sought to quantify its antioxidant capacity, antibacterial activity, and swelling ratio upon contact with biological fluids—all critical parameters for clot stability and infection prevention. The evaluation was conducted through a multi-scale approach: in vitro Cytotoxicity tests on human adult epidermal keratinocytes (HaCaT) cell lines confirmed the material's biocompatibility. Results demonstrated significant antibacterial activity, with particularly marked efficacy against the pathogen Klebsiella pneumoniae. In vivo application on patients undergoing endovascular procedures validated the device’s effectiveness in the secure closure of arterial access sites. The analysis demonstrates that the Axiostat sponge does not merely act as a mechanical barrier but as a multifunctional medical device. The combination of excellent hemostatic properties, biocompatibility, and antibacterial capacity renders it a high-value clinical tool for optimizing post-operative recovery and reducing infectious complications.

Background/Objectives: The safe completion of a non-invasive procedure is crucial to the success of an endovascular approach. Chitosan, a natural polysaccharide derived from chitin, is an ideal material for the study and application of medical devices in post-operative wound management. Methods: The present work is based on a retrospective study conducted on a sample of patients treated with Axiostat (a sterile, single-use, non-absorbable dressing), composed of 100% chitosan and designed to instantly stop bleeding through a mucus adhesion mechanism for the treatment of conditions such as Leriche’s syndrome. The objective was to evaluate the efficacy and safety of the hemostatic Axiostat dressing in patients undergoing anticoagulant and/or antiplatelet therapy in whom endovascular procedures using the axillary artery as an access site are performed to treat Leriche syndrome. Results: The obtained results showed that Axiostat is safe and effective in promoting hemostasis at the axillary vascular access site even when prolonged hemostasis was required in patients on antiplatelet and anticoagulant therapy. The mean time to hemostasis was 5.75 min in all types of patients considered.

Background/Objectives. Psoriasis is a common chronic skin inflammatory disorder pathogenetically associated with genetic, environmental, and immunological factors. The hallmarks of psoriatic lesions include sustained inflammation related to alterations in the innate and adaptive immune response, uncontrolled keratinocyte proliferation, differentiation, and death, as well as dysregulated crosstalk between immune cells and keratinocytes. In search of novel therapeutic strategies based on the use of natural products and dietary components to combine to the available conventional and innovative therapeutics, we explored the anti-inflammatory, antioxidant, and immunomodulatory activities of Curcumin (CU)-based solid lipid nanoparticles (SLNs) carrying the omega-3 fatty acid linolenic acid (LNA) in an in vitro model of psoriasis that had been previously constructed and characterized by us. Methods. This in vitro model consists of differentiated in vitro THP-1 macrophages (Mφs) and NCTC-2544 keratinocytes exposed or not to conditioned medium (CM) from Mφs treated with the Toll-like receptor-7 ligand imiquimod (IMQ). Results. In Mφs, the treatment with CU-LNA-SLNs inhibited the IMQ-induced expression of proinflammatory cytokines (IL-23, IL-8, IL-6: 43%, 26.5% and 73.7% inhibition, respectively, vs IMQ-treated Mφs), as well as the hyperproliferative response (12.8% inhibition vs IMQ-treated Mφs) and the increase in cell death observed in keratinocytes treated with Mφ-derived CM (64.7% inhibition). Moreover, in the same conditions, CU-LNA-SLNs reverted to control levels of the increased keratinocyte expression of two markers of ferroptosis, a form of death recently involved in the pathogenesis of psoriasis (TFRC and MDA: 13.4% and 56.1% inhibition, respectively). Conclusions. These results suggest that CU-LNA-SLNs could inhibit psoriatic inflammation, as well as the hyperproliferation and death of keratinocytes in psoriatic lesions, and could be considered as a new possible therapeutic strategy for psoriasis to be further evaluated for the topic treatment of psoriatic skin in vivo.

Cosmetic products contain numerous metals used as pigments, UV filters, preservatives, antiperspirants and antimicrobial agents, which are responsible for allergic skin reactions, with the most common being nickel. To reduce skin penetration of Ni, innovative pharmaceutical formulations such as lipogels with chelating action against the metal ions themselves can be used. Chelation therapy allows a chelating agent to combine with metal ions to form a stable ring structure called a chelate. The chelate structure is more soluble in water than the toxic metal, which facilitates removal of the toxic metal from the tissue and its excretion by the kidneys. The aim of the following work was to evaluate the chelating properties against nickel ions of different types of lipogels containing flavonoids such as resveratrol and epigallocatechin gallate with chelating activities largely dependent on the number and position of their hydroxyl groups. The results obtained showed that lipogels based on epigallocatechin gallate show high chelating action against nickel, especially at low concentrations. In addition, rheological studies showed an ideal profile to ensure viscoelasticity and swelling of the lipogel within 48 h, confirming reports of 75% epigallocatechin release from the lipogel after 48 h. Tests have shown that lipogels based on epigallocatechin gallate have high chelating action against nickel, especially at low concentrations.

Resveratrol is a naturally occurring phytoalexin found in red grapes, cocoa berries, and red grape wine. This compound exhibits potent antioxidant, anti-inflammatory, and anticancer properties. However, its clinical application is significantly hindered by poor aqueous solubility and rapid degradation at physiological pH, resulting in extremely low systemic bioavailability. This review explores three key aspects: green extraction methods for the efficient and sustainable isolation of resveratrol; structure–activity relationship studies of resveratrol derivatives to identify compounds with improved bioavailability and therapeutic efficacy; and advanced drug delivery systems to enhance resveratrol solubility, stability, and achieve targeted tissue delivery. All of these solutions collectively aim to increase resveratrol bioavailability, enabling the development of effective pharmaceutical formulations and maximizing the clinical potential of this promising compound. The aim of this review is to summarize the key studies published in the last five years, highlighting innovative advancements in sustainable extraction, structural modifications, and delivery strategies for resveratrol.

Hyaluronic acid (HA) is a natural, linear, polysaccharide, formed by repetitions of d-glucuronic acid and D-N-acetylglucosamine. It is the major component of extracellular matrix and essential for many tissues. Its derivatives are widely used in medicine, drug delivery, and tissue engineering thanks to their characteristics such as biocompatibility, biodegradability, nonimmunogenicity, and versatility. On the other hand, being the hydrogels constituted only by HA not stable, chemical modifications, covalent cross-linking, and gelling agents are needed in order to obtain their stability. Therefore, different strategies for obtaining physical and chemical HA hydrogels have been developed, such as click chemistry reactions, enzymatic and disulfide cross-linking, supramolecular assembly via inclusion complexation, and so on. HA-based hydrogels are so attractive and versatile materials for drug delivery, tissue engineering, regenerative medicine, cell therapy, and diagnostics. In particular, the overexpression of HA receptors on various tumor cells makes them promising drug delivery systems for targeted cancer therapy. In this context, the aim of the present chapter is to report the recent advances regarding the design of chemical and physical HA-based hydrogels and, particularly, their various applications for drug delivery and tissue engineering.

Mesoporous silica nanoparticles (MSNs) are promising drug carriers for cancer therapy. Their functionalization with ligands for specific tissue/cell targeting and stimuli-responsive cap materials for sealing drugs within the pores of MSNs is extensively studied for biomedical and pharmaceutical applications. The objective of the present work was to establish MSNs as ideal nanocarriers of anticancer drugs such as 5-FU and silymarin by exploiting characteristics such as their large surface area, pore size, and biocompatibility. Furthermore, coating with various biopolymeric materials such as carboxymethyl chitosan-dopamine and hyaluronic acid-folic acid on their surface would allow them to play the role of ligands in the process of active targeting to tumor cells in which there is an overexpression of specific receptors for them. From the results obtained, it emerged, in fact, that these hybrid nanoparticles not only inhibit the growth of glioblastoma and breast cancer cells, but also act as pH-responsive release systems potentially useful as release vectors in tumor environments.

Melanoma is one of the most aggressive forms of skin cancer, which is characterized by metastasis and poor prognosis due to the limited effectiveness of current therapies and the toxicity of conventional drugs. For this reason and in recent years, one of the most promising strategies in the treatment of this form of cancer is the use of drug delivery systems as carriers capable of conveying the therapeutic agent into the tumor microenvironment, thus preventing its degradation and improving its safety and effectiveness profiles. In the present work, microparticles based on silk fibroin and epifibroin 0039, silk-derived proteins loaded with idebenone, were created, which act as therapeutic carriers for topical use in the treatment of melanoma. The resulting particles have a spherical shape, good loading efficiency, and release capacity of idebenone. Efficacy studies have demonstrated a reduction in the proliferation of COLO-38, melanoma tumor cells, while safety tests have demonstrated that the microparticles are not cytotoxic and do not possess prosensitizing activity. Notably, transdermal release studies revealed that all particles released idebenone over more days. The analysis of the stimulatory markers of the proinflammatory process, CD54 and CD86, did not show any increase in expression, thus confirming the absence of potential prosesensitization effects of the silk fibroin-based particles. The research, therefore, found that idebenone-loaded silk protein microparticles could effectively reduce the proliferation of melanoma cells without cytotoxicity. This indicates the promise of a safe and effective treatment of melanoma.

Wounds caused by trauma and/or surgery represent a significant challenge in contemporary medical practice, requiring innovative approaches to promote optimal healing and reduce the risk of bleeding and complications resulting from it. In this context, chitosan, a natural polysaccharide derived from chitin, represents an ideal material for the study and application of medical devices, in the form of dressings, in wound management for pre- and/or post-operative wounds due to its ability to induce hemostasis and its high biocompatibility with biological tissues. The aim of this work was to discuss the structural characteristics, properties and application of chitosan-based hemostatic dressings in hemostatic processes resulting from pre- or post-surgical approaches.

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia caused by abnormalities in insulin secretion and/or action. In patients with diabetes, complications such as blindness, delayed wound healing, erectile dysfunction, renal failure, heart disease, etc., are generally related to an increase in ROS levels which, when activated, trigger hyperglycemia-induced lesions, inflammation and insulin resistance. In fact, extensive cell damage and death occurs mainly due to the effect that ROS exerts at the level of cellular constituents, causing the deterioration of DNA and peroxidation of proteins and lipids. Furthermore, elevated levels of reactive oxygen species (ROS) and an imbalance of redox levels in diabetic patients produce insulin resistance. These destructive effects can be controlled by the defense network of antioxidants of natural origin such as phloretin and gallic acid. For this reason, the objective of this work was to create a nanocarrier (hydrogel) based on gallic acid containing phloretin to increase the antioxidant effect of the two substances which function as fundamental for reducing the mechanisms linked to oxidative stress in patients suffering from chronic diabetes. Furthermore, since the bioavailability problems of phloretin at the intestinal level are known, this carrier could facilitate its release and absorption. The obtained hydrogel was characterized using Fourier transform infrared spectroscopy (FT-IR). Its degree of swelling (a%) and phloretin release were tested under pH conditions simulating the gastric and intestinal environment (1.2, 6.8 and 7.4). The antioxidant activity, inhibiting lipid peroxidation in rat liver microsomal membranes induced in vitro by a free radical source, was evaluated for four hours. All results showed that gallate hydrogel could be applied for releasing intestinal phloretin and reducing the ROS levels.

Background: Hypertension affects 32% of adults worldwide, leading to a significant global consumption of cardiovascular medications. Atenolol, a β-adrenergic receptor blocker, is widely prescribed for cardiovascular diseases such as hypertension, angina pectoris, and myocardial infarction. According to the Biopharmaceutics Classification System (BCS), atenolol belongs to Class III, characterized by high solubility but low permeability. Currently, atenolol is commercially available in oral formulations. Increasing attention is being directed towards developing cost-effective transdermal delivery systems, due to their ease of use and better patient compliance. Eutectogels represent next-generation systems that are attracting great interest in the scientific community. Typically obtained from deep eutectic solvents (DESs) combined with gelling agents, these systems exhibit unique properties due to the intrinsic characteristics of DESs. Methods: In this study, a DES based on choline chloride as a hydrogen bond acceptor (HBA) and propylene glycol as a hydrogen bond donor (HBD) was explored to enhance the topical delivery of atenolol. The solubility of atenolol in the DES was evaluated using spectroscopic and thermodynamic measurements which confirmed the formation of hydrogen bonds between the drug and DES components. Additionally, the safety of the DES was assessed in a cell viability assay. Subsequently, we formulated eutectogels with different concentrations using animal gelatin and Tego Carbomer 140, and characterized these formulations through rheological measurements, swelling percentage, and permeation studies with Franz cells. Results: These novel eutectogels exhibit superior performance over conventional hydrogels, with a release rate of approximately 86% and 51% for Carbomer- and gelatin-based eutectogels, respectively. In contrast, comparable hydrogels released only about 27% and 35%. Conclusions: These findings underscore the promising potential of eutectogels for the transdermal delivery of atenolol.

Rapid haemostasis during surgery is essential when one wants to reduce the duration of operations, reduce the need for transfusions, and above all when one wants to achieve better patient management. The use of haemostatic agents, sealants, and adhesives improves the haemostatic process by offering several advantages, especially in vascular surgery. These agents vary widely in their mechanism of action, composition, ease of application, adhesion to wet or dry tissue, immunogenicity, and cost. The most used are cyanoacrylate-based glues (Glubran 2) or polysaccharide hydrogel-microsphere powder (AristaTMAH). This work is based on a retrospective study carried out on a sample of patients with different vascular diseases (FAV, pseudoaneurysm, and PICC application) in which two different haemostatic sealants were used. The aim was to assess the safety, the advantages, and the ability of both sealants to activate the haemostatic process at the affected site, also in relation to their chemical-physical characteristics. The obtained results showed that the application of Glubran 2 and AristaTMAH as surgical wound closure systems is effective and safe, as the success achieved was ≥94% on anastomoses of FAV, 100% on stabilization of PICC catheters, and ≤95% on pseudoaneurysms.

The aim of this work was to evaluate the antineoplastic effect of newly synthesized nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) alone or PLGA esterified with 2,2′-[propane-2,2-diylbis (thio)] diacetic acid (TKL), loaded with docetaxel (DTX) and/or docosahexaenoic acid (DHA), as innovative site-specific therapeutic carriers. The obtained materials were characterized by FT-IR and 1H-NMR, while the dimensional analysis of the nanoparticles obtained was performed by Dynamic Light Scattering. The encapsulation efficiency of the nanoparticles was evaluated, and in vitro skin permeation tests were also performed. The antitumor activity of the nanomaterial was studied in the human adenocarcinoma HCT116 cell line. In particular, viability tests in bidimensional culture, as well as in tumor spheroids, were conducted. The use of these nanocarriers could facilitate the stable and efficient delivery of DTX and DHA through the upper segments of the gastrointestinal tract to the colon. In addition, the presence of the ROS-sensitive 2,2′-[propane-2,2-diylbis (thio)] diacetic acid in their matrix should promote the site-specific release of DTX in the tumor mass, where high levels of reactive oxygen species could be found.

The development of biomedical applications is a transdisciplinary field that in recent years has involved researchers from chemistry, pharmacy, medicine, biology, biophysics, and biomechanical engineering. The fabrication of biomedical devices requires the use of biocompatible materials that do not damage living tissues and have some biomechanical characteristics. The use of polymeric membranes, as materials meeting the above-mentioned requirements, has become increasingly popular in recent years, with outstanding results in tissue engineering, for regeneration and replenishment of tissues constituting internal organs, in wound healing dressings, and in the realization of systems for diagnosis and therapy, through the controlled release of active substances. The biomedical application of hydrogel membranes has had little uptake in the past due to the toxicity of cross-linking agents and to the existing limitations regarding gelation under physiological conditions, but now it is proving to be a very promising field This review presents the important technological innovations that the use of membrane hydrogels has promoted, enabling the resolution of recurrent clinical problems, such as post-transplant rejection crises, haemorrhagic crises due to the adhesion of proteins, bacteria, and platelets on biomedical devices in contact with blood, and poor compliance of patients undergoing long-term drug therapies.