Hydrogels For Delivery Research Articles

Laboratory synthesis and preparation of thermo-responsive polymeric micelle and hydrogel for resveratrol delivery and release

Laboratory synthesis and preparation of thermo-responsive polymeric micelle and hydrogel for resveratrol delivery and release

Hydrogel for Sustained Delivery of Therapeutic Agents

In recent years, hydrogels have emerged as a highly promising platform for the sustained delivery of therapeutic agents, addressing critical challenges in drug delivery systems, from controlled release to biocompatibility [...]

Amphiphilic Gelator-Based Shear-Thinning Hydrogel for Minimally Invasive Delivery via Endoscopy Catheter to Remove Gastrointestinal Polyps.

Injectable polymeric hydrogels delivered via endoscopic catheter have emerged as promising submucosal agents, offering durable, long-lasting cushions to enhance the efficacy of endoscopic submucosal dissection (ESD) for the removal of small, flat polyps from the gastrointestinal tract (GIT). However, polymer-based injections do not meet the easy-injectability criteria via catheter because their high viscosity tends to clog the catheter needle. To the best of knowledge, for the first time, report the fabrication of an amphiphile-based small molecule hydrogel of diglycerol monostearate (DGMS)thatself-assembles to form hydrogel (DGMSH) for delivery via an endoscopic catheter. Physicochemical characterization of the hydrogel reveals its fibrous morphology, shear-thinning behaviour, and easy injectability, along with its scalability and long shelf-life (6 months). Ex vivo studies on the goat's stomach and intestine demonstrate the ease of injectability through the catheters and the development of visible submucosal cushion depots with the desired height. Moreover, the hydrogel can encapsulate both hydrophobic and hydrophilic drugs/dyes. In vivo studies in small animals have found that the hydrogel depot is durable, biocompatible, non-immunogenic, and has a hemostatic effect. Endoscopic studies in the porcine model demonstrate a safe injection and endoscopic excision of GI polyps acting as a suitable agent for ESD.

Chitosan-based self-healing thermosensitive hydrogel loaded with siHMGB1 for treatment of rheumatoid arthritis via macrophage repolarization.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease marked by immune cell activation, particularly macrophages. An imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages causes synovial inflammation and joint damage, worsening RA. This study presents a biomacromolecular hydrogel delivery system with apoferritin nanoparticles for effective delivery of small interfering high mobility group protein (siHMGB1). The system was designed to promote the polarization of M1 macrophages to the M2 phenotype by downregulating the HMGB1/TLR4/NF-κB-p65 signaling pathway, offering a potential therapeutic approach for the treatment of RA. The oxidized chondroitin sulfate - chitosan - sodium glycerol β - phosphate - Fn/siHMGB1 (OCF/siHMGB1) hydrogel system possessed temperature-sensitive and self-healing properties, enabling the sustained, stable, and efficient release of siHMGB1 at the affected joint. After effective uptake by macrophages, siHMGB1 could effectively repolarize M1-phenotype macrophages to M2-phenotype via the HMGB1/TLR4/NF-κB-p65 signaling pathway both in vitro and in vivo. Additionally, it suppressed the release of pro-inflammatory cytokines and upregulated anti-inflammatory cytokines, which significantly blocked the TLR4/p65-mediated inflammatory signaling. In conclusion, the siHMGB1-loaded hydrogel delivery system designed in this study is effective in treating RA and highlights the potential of gene therapy to induce repolarization of M1 to M2 macrophages for RA treatment.

Alginate-chitosan hydrogel formulations for VEGFA expressed baculovirus delivery promoting angiogenesis for wound healing and revascularization

Abstract Background Baculoviruses, engineered to express growth factors, offer a promising avenue for short-term gene therapy, such as wound dressings, due to their safety and specificity. Encapsulation in natural polymers like alginate and chitosan addresses limitations like serum inactivation and fragility, while promoting sustained delivery and shielding from immune inactivation. Wound healing involves complex processes that can be enhanced by maintaining an antimicrobial, moist environment, which promotes cell migration and angiogenesis. Vascular endothelial cell growth factor A (VEGFA) is known to be one of the most potent pro-angiogenic factors and plays a key role in wound healing. Purpose This investigation seeks to enhance wound healing and angiogenesis, support the revascularization process, and provide anti-inflammatory and anti-microbial effects. Additionally, it aims to assess the preclinical efficacy and safety of the approach. Methods Ionic cross-linking was used for virus encapsulation under aseptic conditions. The capsules were assessed for their surface morphology, particle size, zeta potential, and in vitro release profile. Additionally, their therapeutic potential was studied using cell lines. The efficacy of hydrogel delivery of VEGFA-expressing baculoviruses in promoting cell migration and angiogenesis for wound healing applications was investigated on Human Umbilical Vein Endothelial Cells (HUVECs). Hydrogel morphology, swelling, and encapsulation efficiency were evaluated, along with endothelial tube formation assays and hemocompatibility studies on HUVECs. Results Encapsulation of baculovirus expressing the VEGFA gene in alginate and chitosan–alginate hydrogels achieve a high encapsulation efficiency of 99.9%. This allows for prolonged virus delivery and an increased therapeutic window. The encapsulated baculovirus maintains activity and is released over eight days, with a transduction efficiency of over 40%. This promotes tube formation, cell proliferation, and cell migration for angiogenesis, particularly beneficial for chronic wound-healing applications. The hydrogels also prevented E. coli and C. albicans growth directly below and inhibited C. albicans growth surrounding the alginate–chitosan hydrogels. The hydrogels demonstrated no cytotoxicity and good blood compatibility. Conclusion This proof of concept underscores the potential of encapsulated baculovirus delivery systems for various gene therapy applications including cardiovascular tissue regeneration and revascularization.

Temperature‐Responsive Injectable Hydrogels Containing Gelatin and Cell Adhesion Peptides for Adipose‐Derived Stem Cell Delivery

ABSTRACTResearch on injectable polymers (IPs) has been actively conducted in recent decades for biomedical applications. Temperature‐responsive IPs are especially effective because they can be gelled by injecting them into a living organism without external contamination. Adipose‐derived stem cells (AdSCs) can be easily harvested in a minimally invasive manner and differentiated into various cell lineages. Versatile therapeutic applications have been developed through the secretion of various cytokines from AdSCs. In this study, we prepared IP hydrogels comprising a temperature‐responsive polymer with reactive succinimide groups (tri‐PCG‐OSu), a biomacromolecule (gelatin) as a crosslinker, and Pluronic with RGDS peptide (PL‐RGDS) as a cell adhesion factor to extend the duration of the gel state and improve cell engraftment in the IP hydrogels for AdSC delivery. The combined use of gelatin and cell adhesion peptides in the polymer matrix improved the fraction of living cells encapsulated in the IP hydrogels and increased the expression levels of angiogenic factors in AdSCs cultured within them. We also presume that a certain number of cells in the IP hydrogels could be differentiated into adipocytes using the differentiation‐inducing medium. These results suggest that our temperature‐responsive IP system could be used as a cell delivery material for regenerative medicine.

Nanozyme Hydrogels Promote Nerve Regeneration in Spinal Cord Injury by Reducing Oxidative Stress.

Inhibiting secondary cell death and promoting neuronal regeneration are critical for nerve repair after spinal cord injury (SCI). The excessive accumulation of reactive oxygen species (ROS) after SCI causes cell death and induces apoptosis. These reactions further increase the level of ROS production, leading to a vicious cycle of spinal cord tissue damage. Therefore, intervention targeting ROS is a potential therapeutic approach to improve the recovery of locomotor function after SCI. In this study, we designed and synthesized a nanozyme hydrogel delivery system loaded with multiple drugs, LA/Me/Se NPs-h. LA/Me/Se NPs-h exhibited a satisfactory size distribution and excellent stability, enhancing the bioavailability of therapeutic drugs. Moreover, we explored the antioxidant and protective effects of LA/Me/Se NPs-h against oxidative stress-induced cell damage caused by ROS production after SCI in vitro. In the mice SCI model, the Basso mouse scale and gait analysis showed that LA/Me/Se NPs-h significantly promoted the recovery of locomotor function after SCI. The histological and immunofluorescence results of the injury site revealed that LA/Me/Se NPs-h upregulated the expression of GFAP, NF-200, and superoxide dismutase in spinal cord lesion, reduced caspase-3 expression, improved spinal cord continuity, reduced lesion cavity, and inhibited the axonal demyelination. Consequently, LA/Me/Se NPs-h increased the activity of antioxidant enzymes and reduced neuronal apoptosis by reducing oxidative stress and ultimately promoted nerve regeneration. Taken together, this study demonstrated promising nanozyme hydrogels and provided an effective therapeutic strategy for SCI and other ROS-related diseases.

Fluconazole-loaded Hyaluronic Acid-modified Transfersomal Hydrogels Containing D-panthenol for Ocular Delivery in Fungal Keratitis Management.

Fungal keratitis (mycotic keratitis) is an eye infection in which the cornea is infected by fungi and such fungal keratitis management can be effectively possible by ocular administration of antifungal drugs. The main objectives of the present research were to develop and evaluate fluconazoleloaded transfersomal hydrogels for ocular delivery in the effective management of fungal keratitis. A 23 factorial design-based approach was used for statistical optimization, where (A) the ratio of lipid to edge activators, (B) the amount of hyaluronic acid (% HA), and (C) the ratio of edge activators (sodium deoxycholate to Span 80) were taken as three factors. The average vesicle diameter (Z, nm) of transfersomes was taken as a response. Further, fluconazole-loaded transfersomes (FTO) were incorporated into 1% Carbopol 940-based hydrogel (OF1) and 2% HMPC K4M-based hydrogel (OF2) containing D-panthenol (5% w/w). The optimal variable setting for the optimized formulations of FTO was (A) = 9.15, (B) = 0.30%, and (C) = 3.00. FTO exhibited 66.39 nm Z, 0.247 polydispersity index, - 33.10 mV zeta potential, and 65.38 ± 1.77 % DEE, and desirable elasticity. TEM image of FTO demonstrated a unilamellar vesicular structure. The ex vivo ocular permeation of fluconazole from transfersomal hydrogels was sustained over 24 h. All the transfersomal hydrogels showed good bioadhesion and excellent antifungal activity with respect to the zone of inhibition against Candida albicans than Aspergillus fumigates, in vitro. HET-CAM study results demonstrated that both the hydrogels were nonirritant and safe for ocular. Short-term physical stability study suggested the stability of the developed formulation. The current research demonstrated a new way to enhance the ocular penetration of fluconazole via transfersomal hydrogel formulations for ocular delivery in the effective management of fungal keratitis.

Mannose coated selenium nanoparticles normalize intestinal homeostasis in mice and mitigate colitis by inhibiting NF-κB activation and enhancing glutathione peroxidase expression

Impaired intestinal homeostasis is a major pathological feature of inflammatory bowel diseases (IBD). Mannose and selenium (Se) both demonstrate potential anti-inflammatory and anti-oxidative properties. However, most lectin receptors bind free monosaccharide ligands with relatively low affinity and most Se species induce side effects beyond a very narrow range of dosage. This has contributed to a poorly explored therapies for IBD that combine mannose and Se to target intestinal epithelial cells (IECs) for normalization gut homeostasis. Herein, a facile and safe strategy for ulcerative colitis (UC) treatment was developed using optimized, mannose-functionalized Se nanoparticles (M-SeNPs) encapsulated within a colon-targeted hydrogel delivery system containing alginate (SA) and chitosan (CS). This biocompatible nanosystem was efficiently taken up by IECs and led to increased expression of Se-dependent glutathione peroxidases (GPXs), thereby modulating IECs’ immune response. Using a mouse model of DSS-induced colitis, (CS/SA)-embedding M-SeNPs (C/S-MSe) were found to mitigate oxidative stress and inflammation through the inhibition of the NF-kB pathway in the colon. This stabilized mucosal homeostasis of IECs and ameliorated colitis-related symptoms, thereby providing a potential new approach for treatment of IBD.

Self-assembled mixed nanomicelles based hydrogel for enhanced transdermal bioavailability of allopurinol in gout therapy: In vitro and In vivo evaluation

Allopurinol (ALP), a preferred first line medication for the treatment of gout and hyperuricemia, exhibits poor solubility, a short half-life, and undergoes the hepatic first-pass effect, thus resulting in low oral bioavailability. Additionally, ALP is associated with several adverse effects, including hypersensitivity reactions, gastrointestinal issues, and hepatotoxicity. Here, we developed methoxy poly (ethylene glycol)- poly(lactide) (mPEG-PLA)/D-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed nanomicelles (MNs)-based hydrogel for transdermal delivery of ALP to enhance its bioavailability, In vivo safety, and efficacy for gout treatment. To this end, mPEG-PLA diblock copolymer was synthesized via ring-opening copolymerization and characterized using Fourier transform infrared spectroscopy (FTIR), SEM micrograph, proton nuclear magnetic resonance (1H NMR) and Differential scanning calorimetric thermograms (DSC) analysis. Self-assembled mixed nanomicelles were formulated by thin film dispersed technique. The optimized mixed nanomicelles were analyzed for their physicochemical properties and subjected to in vitro, ex vivo and in vivo investigations. The final formulation (ALP-loaded MNs) exhibited a size of 59.12 nm, an encapsulation efficiency (EE) of 87 %, a PDI of 0.053, and a zeta potential of −22.3 mV. In Vitro release kinetics of the ALP-loaded MNs exhibited a sustained and site-specific release profile (p < 0.001). As compared with the ALP based hydrogel, 32-fold higher permeation flux was noticed from ALP-MNs loaded hydrogel with argan oil (ALP-MNs-AO-HG). The in vivo skin irritation study showed that the ALP-MNs-HG was well-tolerated with minimal signs of edema or erythema. ALP-MNs-AO-HG notably enhanced ALP bioavailability with a 7.67 ± 0.01 fold higher AUC0−t, 4.8 ± 0.03 fold longer mean residence time, and a 6 ± 0.04 fold extension in half-life as compared to the oral drug suspension. These results indicate that ALP-MNs based transdermal hydrogels exhibit the potential to enhance therapeutic outcomes by increasing bioavailability and abating the adverse effects associated with oral administration.

Multifunctional conductive stem cell delivery hydrogel combined with low-frequency pulsed electromagnetic fields for spinal cord injury repair

Spinal cord injury (SCI) is a severe traumatic disease for which no satisfying treatment is available. The severe inflammatory reactions and poor endogenous regenerative capacity cause difficulty in functional recovery. Neural stem cells (NSCs) transplantation is currently a promising treatment for repairing SCI. However, there is a lack of effective ways to improve the survival rates of NSCs and promote the neuron differentiation rates of NSCs. Conductive hydrogel can mimic environment which is suitable for neurodevelopment. Low-frequency pulsed electromagnetic fields (LPEMFs) have the advantages of safety, non invasiveness, and tissue repair, making it a potential method of repairing SCI. In this study, an injectable, self-healing magnetic, and conductive hydrogel was synthesized to carry out NSCs with LPEMFs for repairing SCI. In vitro experiments, under the treatment of LPEMFs and conductive hydrogel, the microglia tend to polarize into M2 phenotype, rather than M1 phenotype. Meanwhile, NSCs tend to differentiate into neuronal direction. In SCI model, conductive hydrogel loaded with NSCs combined with LPEMFs can promote functional recovery, through reducing inflammation and promoting neuron differentiation of NSCs. This study provides a novel NSCs transplantation strategy combined with physical interventions for SCI treatment, which brings a new desire to repair SCI.

Cutting-edge developments in the application of hydrogels for treating skin photoaging

Skin photoaging, caused by prolonged exposure to ultraviolet (UV) radiation, manifests as intricate biological transformations, encompassing oxidative damage and structural alterations. Despite a growing need for effective interventions, the existing therapeutic repertoire for treating skin photoaging remains constrained. Recent investigations have shifted focus towards the application of hydrogels as a novel avenue for addressing this concern. Various active substances can be combined with hydrogels for transdermal delivery, including compounds from the ocean, plants, cell active substances, which can promote skin UV damage repair mainly through antioxidant, anti-inflammatory and promote collagen production. This review seeks to offer a thorough summary of recent progress in employing hydrogels for addressing skin photoaging. Topics covered include the mechanism of skin photoaging, and emerging trends in hydrogel-based therapies for skin rejuvenation. The discussion also explores challenges and outlines potential future directions in leveraging hydrogels as therapeutic agents to address skin photoaging.

Ascorbyl palmitate nanofiber-reinforced hydrogels for drug delivery in soft tissues

Nanofiber-based hydrogel delivery systems have recently shown great potential in biomedical applications, specifically due to their high surface-to-volume ratio of ultra-fine nanofibers and their ability to carry low solubility drugs. Herein, we introduce a visible light-triggered in situ-gelling drug vehicle (GAP Gel) composed of ascorbyl palmitate (AP) nanofibers and gelatin methacryloyl polymer. AP nanofibers form self-assembled structures through intermolecular interactions with a hydrophobic drug-loading core. We demonstrate that the hydrophilic periphery of AP nanofibers allows them to interact with other hydrophilic molecules via hydrogen bonds. The presence of AP nanofibers significantly enhances the viscoelasticity of GAP Gel in a concentration-dependent manner. Further, GAP Gel shows in vitro biocompatibility and sustained drug delivery efficacy when loaded with a hydrophobic antibiotic. Likewise, GAP Gel shows excellent in vivo biocompatibility when implanted in immunocompetent mice in various forms. Lastly, GAP Gels maintain cell viability when cultured in a 3D-environment over 7 days, establishing it as a promising and versatile hydrogel platform for the delivery of biotherapeutics.

Injectable Alginate-Based Hydrogels Encapsulating Engineered Endothelial Extracellular Vesicles for the Treatment of Critical Limb Ischemia.

Critical limb ischemia (CLI) is a peripheral arterial disease resulting from chronic inflammation of vascular systems. Recent studies have shown that inhibiting macrophage inflammation has the potential to treat CLI, and extracellular vesicles (EVs) from endothelial cells can inhibit macrophage activation. However, the limited cell-targeting capabilities and rapid clearance of EVs from the injection site limit the in vivo application of the EVs. Here, we modified endothelial EVs with platelet membranes (pM/EVs) to boost the inhibition effects on macrophage inflammation and developed an injectable alginate-based collagen composite (ACC) hydrogel for localized delivery of pM/EVs (pM/EVs@ACC) for CLI treatment. We found that pM/EVs can effectively inhibit macrophage inflammation in vitro. Furthermore, pM/EVs@ACC treatment significantly promotes the recovery of limb functions, restoring the feet' blood supply and relieving inflammation. Our findings provide compelling evidence that the pM/EVs@ACC injectable system mediating delivery of pM/EVs is a promising strategy for CLI treatment.

On-Demand Removable Chitosan Based Self-Healing and Antibacterial Hydrogel for Delivery of Tetracycline and Curcumin As Potential Wound Dressing Material.

Wound care is a flourishing branch of healthcare wherein a great amount of research is devoted to develop competent wound dressings. Safe, cost-effective, and biocompatible dressings aid in wound healing without inflicting external trauma and subsequent scar formation. Toward this, we have attempted to develop robust wound dressing material with self-healing and antibacterial properties. We have cross-linked chitosan with 4-formyl phenylboronic acid (4-FPBA) and in situ generated dehydroascorbic acid (DHA) utilizing the dynamic imine and boronate ester linkages. Displaying a channeled microstructure in the SEM micrographs, the hydrogel exhibits a massive water uptake capacity of ∼900% at acidic pH. The hydrogel could completely self-heal within 3 min, and the results are further supported by rheological analysis. By virtue of positive surface charge, it shows a promising tissue adhesive property. Moreover, it affords clean and compliant removal from the wound surface via dissolution induced by dopamine to potentially reduce secondary scarring from peeling of wound dressings. The dressing could significantly act against skin infections caused by S. aureus bacteria with enhanced antimicrobial efficiency via loading of antibiotic drug, tetracycline hydrochloride. A sustained release of tetracycline and Curcumin was observed, which demonstrated the release ability for hydrophilic and hydrophobic bioactive agents. In-vitro studies revealed 93% cell viability with a hemolytic ratio as low as 2.5%, thereby presenting a good self-healing and biocompatible material for wound healing.

Phytic acid-loaded polyvinyl alcohol hydrogel promotes wound healing of injured corneal epithelium through inhibiting ferroptosis

As the important barrier of intraocular tissue, cornea is easy to suffer various kinds of injuries. Among them, acute alkali burn is a thorny ophthalmic emergency event, which can lead to corneal persistent epithelial defects, ulcers, and even perforation. Ferroptosis, a mode of regulatory cell death, has been found to play a key role in the process of corneal alkali burn, of which lipid peroxidation and intracellular iron levels are considered to be the possible therapeutic targets. To seek new effective treatments, the study herein focused on the occurrence of oxidative stress and ferroptosis in corneal alkali burn, exploring the role of phytic acid (PA), a natural small molecule with both antioxidant and iron chelating capacity, in the repair of corneal epithelial injury. The in vivo therapeutic results showed that PA eyedrops treatment promoted the recovery of corneal morphology and function, and in vitro experiments proved that PA prompted the repair of oxidative stress induced-corneal epithelial injury through ferroptosis inhibition. In addition, better drug treatment effect could be achieved through hydrogel delivery and sustained release, and our in vivo experiments showed the superior therapeutic effects of PA delivered by PVA hydrogels with larger molecular weights on corneal injury. In summary, this study demonstrated the excellent effect of natural small molecule PA with antioxidant and high efficiency chelating ferrous ions on ferroptosis inhibition, and showed the outstanding application prospect of PVA/PA hydrogels in the treatment of corneal epithelial injury.

The Application of Nanotechnology for the Diagnosis and Treatment of Endocrine Disorders: A Review of Current Trends, Toxicology and Future Perspective.

The endocrine system regulates many biological systems, and disruptions may result in disorders, such as diabetes, thyroid dysfunction, Cushing's syndrome, and obesity. The total incidence of endocrine illnesses was found to be 47.4%, excluding type 2 diabetes mellitus, with a significant frequency of newly diagnosed endocrine disorders. Nanotechnology manipulates particles at the atomic and molecular levels, opening up new paths for studying disease etiology and therapeutic alternatives. The goal of using nanomaterials in the treatment of endocrine illnesses is to create endogenous nano-biosensors that can detect even modest changes in hormone levels and react spontaneously to restore normal function. The size and surface characteristics of nanoparticles enhances the sensitivity in nano-sensors and are functionalized for targeted drug delivery. Nano-sized carriers composed of lipids, polymers, carbon, or metals have been shown to work much better than standard drug delivery methods. Nanoparticles (NPs) offer various advantages over current methods for diagnosing and treating endocrine disorders, acting as hydrogels for insulin delivery and wound healing. Incorporating selenium NPs into inorganic nanoparticles enhances their bioactivity and targeted delivery. Gold NPs show a promising precise insulin delivery. Mesoporous silica NPs maintain glycemic level effectively and lipid and polymeric NPs protect drugs from degradation in the gastrointestinal tract. Carbon nanotubes (CNTs) have become popular in thyroid surgeries. These characteristics make nanoparticles valuable for developing effective diagnostic and therapeutic systems. NP-based medicines have been thoroughly researched in order to identify the beginning point for the creation of theranostics, which may function in two ways: as imaging agents or therapeutics. The study posits that nanotechnology bridges diagnostics and therapies, potentially revolutionizing endocrine disorder treatments. This review delves into nanotechnology techniques, emphasizing their applications in diagnosing and treating diabetes mellitus.

Dimethyl Fumarate-Loaded Gellan Gum Hydrogels Can Reduce In Vitro Chemokine Expression in Oral Cells.

Dimethyl fumarate (DMF), originally proposed to treat multiple sclerosis, is considered to have a spectrum of anti-inflammatory effects that effectively control periodontitis, mainly when applied with a hydrogel delivery system. Chemokine expression by gingival fibroblasts is a significant driver of periodontitis; thus, hydrogel-based strategies to deliver DMF, which in turn dampen chemokine expression, are of potential clinical relevance. To test this approach, we have established a bioassay where chemokine expression is induced by exposing gingival fibroblast to IL1β and TNFα, or with saliva. We show herein that DMF effectively reduced the expression of CXCL8, CXCL1, CXCL2, and CCL2-and lowered the phosphorylation of ERK and JNK-without affecting cell viability. This observation was confirmed by immunoassays with CXCL8. Consistently, the forced chemokine expression in HSC2 oral squamous epithelial cells was greatly diminished by DMF. To implement our hydrogel-based delivery system, gingival fibroblasts were cocultured with gellan gum hydrogels enriched for DMF. In support of our strategy, DMF-enriched gellan gum hydrogels significantly reduced the forced chemokine expression in gingival fibroblasts. Our data suggest that DMF exerts its anti-inflammatory activity in periodontal cells when released from gellan gum hydrogels, suggesting a potential clinical relevance to control overshooting chemokine expression under chronic inflammatory conditions.

Arthroscopic device with bendable tip for the controlled extrusion of hydrogels on cartilage defects

Advanced tools for the in situ treatment of articular cartilage lesions are attracting a growing interest in both surgery and bioengineering communities. The interest is particularly high concerning the delivery of cell-laden hydrogels. The tools currently available in the state-of-the-art hardly find an effective compromise between treatment accuracy and invasiveness. This paper presents a novel arthroscopic device provided with a bendable tip for the controlled extrusion of cell-laden hydrogels. The device consists of a handheld extruder and a supply unit that allows the extrusion of hydrogels. The extruder is equipped with a disposable, bendable nitinol tip (diameter: 4 mm, length: 92 mm, maximum bending angle: 90°) that guarantees access to hard-to-reach areas of the joint, which are difficult to get to, with conventional arthroscopic instruments. The tip accommodates a biocompatible polymer tube that is directly connected to the cartridge containing the hydrogel, whose plunger is actuated by a volumetric or pneumatic supply unit (both tested, in this study). Three different chondrocyte-laden hydrogels (RGD-modified Vitrogel®, methacrylated gellan gum, and an alginate–gelatine blend) were considered. First, the performance of the device in terms of resolution in hydrogel delivery was assessed, finding values in the range between 4 and 102 µL, with better performance found for the pneumatic supply unit and no significant differences between straight tip and bent tip conditions. Finite element simulations suggested that the shear stresses and pressure levels generated during the extrusion process were compatible with a safe deposition of the hydrogels. Biological analyses confirmed a high chondrocyte viability over a 7-day period after the extrusion of the three cell-laden hydrogel types, with no differences between the two supply units. The arthroscopic device was finally tested ex vivo by nine orthopedic surgeons on human cadaver knees. The device allowed surgeons to easily deliver hydrogels even in hard-to-reach cartilage areas. The outcomes of a questionnaire completed by the surgeons demonstrated a high usability of the device, with an overall preference for the pneumatic supply unit. Our findings provide evidence supporting the future arthroscopic device translation in pre-clinical and clinical scenarios, dealing with osteoarticular treatments.

Alginate/methacrylic acid/calcium ion-based pH-sensitive drug delivery hydrogel for the treatment of ulcerative colitis

Oral colon-targeted drug formulations play a pivotal role in managing colon diseases, yet the effectiveness of most hydrophobic drug formulations in reaching the colon orally is hindered by challenges such as poor solubility, premature release in the stomach, and low bioavailability. In this study, we devised a pH-sensitive dual-network hydrogel utilizing sodium alginate and methacrylic acid for treating ulcerative colitis. The primary rigid network layer is activated thermally through free radicals, while the secondary flexible network layer is formed by the coordination of alginic acid and calcium ions. Sulfadiazine was loaded into the hydrogels using a solution displacement method. We conducted a comprehensive analysis of the morphology, mechanical properties, and drug release mechanisms of the hydrogels. The hydrogel demonstrated outstanding pH-responsive swelling properties. In acidic environments, protonation of carboxyl groups led to hydrogel network contraction, while in weakly alkaline environments, deprotonation induced electrostatic repulsion, facilitating swelling and controlled drug release. The alteration of pH from 1.2 to 7.4 increased the drug release rate from 33 % to 92 %, aligning with the first-order kinetic release model. The drug-loaded gel exhibited a compressive stress of 0.13 MPa at 50 % strain, and its superior mechanical properties ensured stability before drug release. Moreover, the hydrogel displayed excellent biocompatibility, hemocompatibility, and thermal stability. In summary, these findings underscore the substantial potential of drug-loaded gels in advancing controlled drug delivery systems.