Search Results (781)

Fractures are becoming a bigger and bigger global health problem, with an estimated 178 million new cases each year and 455 million people living with disabilities caused by fractures. Donor site morbidity, the risk of immune rejection, and limited functional integration all make current grafting techniques less effective. Biomaterials that come from nature, like collagen, gelatin, chitosan, alginate, hyaluronic acid (HA), and silk fibroin, have become promising scaffolds because they are bioactive, mimic the extracellular matrix (ECM), and can be broken down by enzymes. Crosslinking and composite reinforcement can greatly change how well they work. For example, collagen scaffolds that are highly crosslinked with glutaraldehyde keep up to 51.9% of their tensile strength after being exposed to enzymes, while non-crosslinked scaffolds only keep 12% of their strength. Chitosan–hydroxyapatite matrices, on the other hand, can reach compressive strengths of 2–12 MPa, which is close to the strength of cancellous bone. Additive manufacturing and 4D printing allow for precise control of structures and the ability to change their shape over time, which helps with vascularization and mechanical adaptation. Injectable and in situ-forming hydrogels show clinically important results, such as filling 85% of osteochondral defects in rabbits, improving left ventricular ejection fraction by up to 9% in large-animal cardiac models, and speeding up healing by 25–40% in chronic wounds. Even with these improvements, it is still hard to get batch consistency, a standardized way to test mechanical properties, and production that meets GMP (Good Manufacturing Practices) standards and can be scaled up. Full article

Peptide-based supramolecular hydrogels have emerged as promising biomaterials due to inherent biocompatibility, tunable self-assembly, and structural similarity to the extracellular matrix. This work describes the design, synthesis and characterization of a library of symmetrical bolaamphiphiles based on dehydropeptides, systematically varying both the dehydroamino acid residue and the linker. Aromatic and aliphatic dicarboxylic acids with distinct rigidities were employed to elucidate their influence on molecular self-assembly, hydrogelation, and functional performance. Hydrogel formation was triggered using a pH-responsive approach, and critical aggregation and gelation concentrations were determined. Morphological analysis by transmission electron microscopy revealed dense fibrillar networks with nanometer-scale fiber diameters, while rheological studies demonstrated viscoelastic behavior, tunable mechanical strength, and, in selected systems, efficient self-healing properties. The incorporation of phenylalanyldehydrophenylalanine significantly enhanced hydrogel formation, highlighting the importance of π–π interactions and hydrophobicity. Biological evaluation using HaCaT keratinocytes confirmed low cytotoxicity across the series. A representative injectable hydrogel exhibited sustained release of the anticancer drug methotrexate, governed predominantly by Fickian diffusion. These results establish clear structure–property–function relationships and demonstrate the potential of symmetrical bolaamphiphilic dehydropeptides as versatile platforms for controlled drug delivery. Full article

The development of multifunctional, mechanically robust, and sustainable hydrogels from renewable biomaterials has attracted increasing attention for advanced biomedical applications; however, achieving an optimal balance between mechanical stability, biofunctionality, and infection control remains challenging. In this work, collagen (COL) extracted from raw trimming wastes from a tannery is used to fabricate COL/PAA/Fe composite hydrogels via the ammonium persulfate (APS)-initiated polymerization of acrylic acid (AA) coupled with Fe³⁺-mediated coordination cross-linking. The resulting hydrogel network is stabilized by synergistic COL-poly(acrylic acid) (PAA) hydrogen bonding and dynamic Fe³⁺–carboxylate coordination, imparting enhanced mechanical strength and elasticity. The optimized hydrogel exhibited maximum tensile and compressive strengths of ~0.176 MPa at 751% elongation and ~1.945 MPa at a strain of 80%, respectively. In addition, a high ionic conductivity of 4.11 S·m⁻¹ is achieved, enabling structural integrity under deformation and suitability for flexible electronic interfaces. The prepared hydrogel also displayed rapid autonomous self-healing behavior and substantial antibacterial properties against both Gram-positive and Gram-negative bacteria. Overall, COL is employed herein as a sustainable precursor, highlighting an eco-conscious approach to biomaterial design. This work presents a versatile strategy for producing mechanically stable and biofunctional hydrogels with strong potential for wound dressing, tissue engineering, and injectable biomedical applications. Full article

Botulinum toxin type A (BoNT/A) injection into the bladder wall is a milestone in the treatment of urinary incontinence in patients with neurogenic detrusor overactivity (NDOi) or overactive bladder syndrome (OABi) who are refractory to or unable to tolerate oral or transdermal therapies. However, the efficacy of BoNT/A is hampered by the low long-term adherence of patients to a treatment that requires repeated bladder injections under cystoscopy control. The discontinuation is particularly evident among incontinent patients with spontaneous voluntary voiding, regardless of whether the cause is NDOi or OABi, although clearly more marked among the latter group. In addition to the bother and pain associated with repeated cystoscopies, these patients show low tolerance to the high incidence of urinary tract infections (UTIs) and transient urinary retention, the two most common adverse events. Fewer injection points may render treatments less painful, apparently without reducing efficacy, but will not avoid the need for repeated cystoscopies, and no studies have demonstrated that such modification increases adherence. Eventually, accessing the bladder wall for BoNT/A administration via a transabdominal approach, under real-time ultrasound guidance, may overcome trans-urethral limitations, but the technique’s reproducibility remains unknown. An intensive investigation is ongoing to identify aids that facilitate the passage of the large, fragile BoNT/A molecule across the urothelium to reach the bladder nerves without injections. Electromotive Drug Administration (EMDA) of BoNT/A demonstrated efficacy and safety over a 6-year follow-up in NDOi patients at a single center, but the results were not reproduced at other institutions. The application of shock waves to the bladder using shock waves generated by Extracorporeal Shock Wave Lithotripsy (ESWL) machines to tear the urothelium and facilitate the passage of BoNT/A instilled in the bladder is ingenious, but the experience is very limited. Dimethyl sulfoxide, liposomes, and thermal-reversal hydrogel to deliver the toxin failed in pilot trials. BoNT/A in nano-formulations has high heat stability, resistance to pH changes, and to enzymatic degradation. Extended efficacy in dermal and intramuscular pilot applications is promising but needs to be replicated in the bladder. Full article

Background: Disease outbreaks remain a major constraint on aquaculture production, making vaccination essential for disease management in farmed fish. However, injectable oil-adjuvanted vaccines can be costly and may induce adverse inflammatory reactions and welfare concerns, motivating investigations into alternative injectable adjuvant materials. Methods: We conducted an in vivo safety evaluation of shear-thinning, amidated TEMPO-oxidized cellulose nanofiber (TO-CNF) hydrogels formulated with an inactivated Vibrio anguillarum bacterin. Formulations were administered intraperitoneally to Atlantic salmon (Salmo salar L.) using a common garden design with cohabitated treatment groups across triplicate tanks. Fish were monitored and sampled at pre-injection baseline and at 300-, and 600-degree days post-injection. Safety endpoints included mortality, macroscopic and histopathological outcomes, and growth evaluated relative to sham controls, unmodified TO-CNF, and a commercial oil-adjuvanted vaccine. Results: Amidated TO-CNF formulations were associated with increased mortality (up to 16–18% in higher reagent-loading groups) compared to commercial oil-adjuvanted vaccine, material, and sham controls. Affected fish exhibited adverse outcomes, including adhesions, proliferative lesions, ascites, edema, hemorrhage, and secondary opportunistic infections. In contrast, controls showed minimal mortality and pathology. Growth and immune response endpoints were variable and did not demonstrate consistent treatment-associated effects. Physicochemical analyses indicated differences in formulation stability and qualitative compositional differences across modification levels, but these were not quantified nor linked to specific causal mechanisms in this study. Conclusions: The amidated TO-CNF formulations tested here were associated with formulation-dependent safety risks under the conditions evaluated and are not yet suitable as injectable vaccine adjuvants in Atlantic salmon. These findings define important safety constraints for this material class and highlight the need for improved modification and purification strategies. More broadly, this work underscores the importance of establishing in vivo safety boundaries prior to efficacy optimization for emerging biomaterial-based vaccine adjuvants. Full article

Background/Objectives: Wound management presents a substantial clinical challenge due to the rising incidence of chronic wounds, infections, and the limitations of conventional dressings in creating an ideal healing microenvironment. This review aims to provide a comprehensive overview of advanced smart hydrogel platforms designed to improve wound healing outcomes, focusing on their capacity to respond adaptively to physiological and external stimuli. Methods: This article analyzes the core characteristics of smart hydrogels, specifically examining stimuli-responsive systems (pH, temperature, enzyme, light, and electricity). The review evaluates advanced configurations—including injectable, self-healing, and 3D-printable systems—and functionalized hydrogels integrated with antimicrobials, drugs, and nanocomposites. Additionally, essential characterization methodologies, biological assessments, and regulatory considerations for clinical translation are synthesized. Results: The literature, which is predominantly preclinical in nature, indicates that functionalized hydrogels significantly enhance tissue regeneration, angiogenesis, and infection control compared to traditional methods. Conductive hydrogels utilizing bioelectrical signals show particular promise in accelerating the healing process. While current clinical applications and commercial products demonstrate efficacy, significant barriers remain regarding large-scale manufacturing and regulatory approval. Conclusions: Smart hydrogels represent a transformative approach to precision wound management, offering superior adaptability and therapeutic delivery. To achieve widespread clinical adoption, future research must address manufacturing scalability and focus on emerging trends, such as the integration of biosensors and AI-powered monitoring systems, to create fully intelligent wound care solutions. Full article

Cartilage regeneration remains an unmet clinical challenge. Despite the great advances in the production of hydrogels as support matrices for cartilage regeneration, the resulting mechanical properties remain low. Granular composite hydrogels appear as ideal candidates due to their injectability and modularity in design. Here, we report on the fabrication and characterization of heterogeneous composite granular hydrogels based on methacrylated chitosan (CHIMA) and gelatin (GelMA) microparticles supported by an interstitial methacrylated alginate (ALMA) matrix. Microparticles were prepared by an oil-emulsion method and their size and morphology optimized, resulting in CHIMA and GelMA microparticles of 10.8 µm (95% CI 9.2, 13.1) and 115.8 µm (95% CI 107.5, 137.6) in diameter, respectively. The microparticles were mixed with ALMA and crosslinked to form granular hydrogels that demonstrated reduced swelling and weight loss. The storage modulus increased from 33 to 66.4 kPa for CHIMA/ALMA hydrogels and from 11.5 to 19.5 kPa for GelMA/ALMA hydrogels when the particle concentration increased from 10 to 50%, and was higher than traditional ALMA hydrogels. Hydrogels of 50:50 CHIMA:GelMA permitted a 6.6-fold increase in cell number after 28 days of culture, and promoted the chondrogenic differentiation of embedded mouse mesenchymal stem cells with a glycosaminoglycan deposition of over 15 µg and the expression of chondrogenic markers. Full article

Myocardial infarction is a major cardiovascular event that leads to heart failure and death. Although current vascular regeneration and pharmacological therapies can salvage some myocardial tissue, they cannot effectively reverse established necrosis, fibrosis, or adverse ventricular remodeling, thus necessitating novel repair strategies. Silk fibroin (SF), a natural biomaterial, has emerged as an ideal substrate for cardiac tissue engineering owing to its excellent biocompatibility, tunable mechanical properties, and controllable biodegradability. This paper systematically reviews SF-based myocardial repair strategies: SF cardiac patches can be directly applied to infarct areas, providing mechanical support and delivering bioactive substances, while injectable SF hydrogels can be formed in situ via minimally invasive methods, serving as three-dimensional delivery vehicles for cells or drugs. These approaches synergistically promote cardiac repair through multiple mechanisms, including active regulation of inflammation, promotion of angiogenesis, and inhibition of fibrosis. Future development of SF-based therapies will focus on creating smart responsive materials, constructing biomimetic structures via advanced biomanufacturing techniques, and accelerating clinical translation, thereby providing comprehensive solutions for myocardial infarction repair. Full article

Background: Polysaccharide-based dynamic hydrogels are promising for wound management due to their biocompatibility, injectability, and tunable biofunctionality. The integration of therapeutic gasotransmitter donors offers a strategy to modulate the wound microenvironment. Objectives: This study aimed to develop an injectable, self-healing carbohydrate hydrogel capable of sustained hydrogen sulfide (H₂S) release for burn wound therapy, and to evaluate its physicochemical properties, in vivo efficacy, and mechanism of action. Methods: A dynamic hydrogel (ACMOD) was fabricated via Schiff-base crosslinking between oxidized dextran (OD) and carboxymethyl chitosan (CMCS), incorporating the H₂S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH). Rheological and recovery tests characterized its mechanical and self-healing properties. Efficacy and mechanisms were assessed in a rat full-thickness burn model, analyzing wound closure, histology, oxidative stress, macrophage polarization, angiogenesis, and collagen deposition. Results: ACMOD exhibited shear-thinning, rapid self-healing, and strong tissue adherence. Sustained H₂S release from ACMOD significantly accelerated wound closure and improved tissue regeneration compared to controls. Mechanistically, H₂S attenuated oxidative stress, promoted a pro-regenerative M2 macrophage phenotype, enhanced angiogenesis via VEGF upregulation, and fostered organized collagen deposition and extracellular matrix remodeling. Conclusions: This work demonstrates a versatile, carbohydrate-based dynamic hydrogel platform that synergizes polymer network dynamics with bioactive H₂S delivery to effectively promote burn wound healing. The findings underscore the potential of polysaccharide hydrogels with integrated gasotransmitter release for regenerative therapy and biomaterials applications. Full article

Optimizing drug administration remains a central challenge in the development of modern therapies, especially in the context of conditions that require spatiotemporal control of active substance release. In this context, hydrogels have been intensively investigated as polymeric platforms for drug delivery, through their three-dimensional hydrophilic structure, tunable properties, and compatibility with biological environments. This analysis presents an integrated approach to hydrogels used in drug administration, addressing the physicochemical fundamentals, the constitutive polymeric materials, and the mechanisms of response to relevant physiological stimuli. Recent experimental studies have been discussed, which highlight the use of hydrogels based on natural, synthetic, and hybrid polymers for controlled and targeted release, in correlation with various administration routes, including oral, injectable, transmucosal, and topical ones. Advanced functionalization strategies that allow adaptive responses to pH, temperature, glucose, enzymes, and reactive oxygen species are also analyzed. Furthermore, emerging directions integrating hydrogels with biosensors, microdevices, and wireless communication systems for real-time monitoring and on-demand release are highlighted. Overall, the analysis emphasizes the role of smart hydrogels as multifunctional platforms for complex therapeutic strategies while also underlining the current challenges associated with clinical translation and long-term performance. Full article

Background: Hyaluronic acid (HA) hydrogels are the most widely used injectable fillers for facial rejuvenation. A new generation of HA fillers crosslinked with poly(ethylene glycol) diglycidyl ether (PEGDE) has been developed to enhance cohesiveness, tissue integration, stability, and longevity while minimizing swelling and immunogenicity. Owing to their distinct viscoelastic properties, PEGDE-crosslinked HA fillers may require product-specific selection and adapted injection techniques. Objective: The objective of this study is to provide practical, expert-based recommendations for the safe and effective use of PEGDE-crosslinked HA hydrogels in facial aesthetic treatments. Methods: A multidisciplinary panel of nine Italian experts in aesthetic medicine, each with more than 15 years of experience using HA fillers, developed consensus recommendations based on clinical practice and available evidence. A pre-meeting questionnaire informed structured discussions during a face-to-face meeting held in Paris in January 2024. The nominal group technique was applied, with consensus defined as agreement by at least 80% of panel members. Results: Consensus was reached on product selection, injection planes, delivery devices, techniques, and typical treatment volumes for PEGDE-HA hydrogels across multiple facial regions, including the forehead, temples, midface, nasolabial folds, chin, jawline, and lips. Recommended injection techniques included microbolus, macrobolus, and retrograde linear threading, with placement ranging from superficial subcutaneous to supraperiosteal planes depending on the anatomical area and clinical indication. Typical injection volumes generally ranged from 0.1 to 0.5 mL per side. Optional ultrasound mapping was considered beneficial in selected high-risk or superficial procedures to improve anatomical safety. Conclusions: These expert consensus recommendations provide practical guidance for clinicians using PEGDE-crosslinked HA hydrogels in facial rejuvenation. Tailoring product characteristics to injection depth, technique, and regional anatomy may help optimize clinical outcomes and procedural safety. Future research priorities include prospective comparative studies with other crosslinking technologies, standardized reporting of adverse events, long-term outcome registries, and further evaluation of ultrasound-guided injection strategies. Full article

Knee osteoarthritis (KOA) is a degenerative joint disorder characterized by chronic inflammation and progressive cartilage degradation. Mesenchymal stem cell (MSC)-based therapies have demonstrated therapeutic potential; however, increasing evidence suggests that their efficacy primarily arises from paracrine factors, highlighting the potential of cell free approaches. In this study, we developed an injectable, thermosensitive composite hydrogel incorporating adipose-derived MSC (AD-MSC) supernatant within a Pluronic F-127 (PF-127)/sodium hyaluronate (HA) matrix. The hydrogel exhibited a solution state at a low temperature and rapidly transitioned into a stable gel at a physiological temperature without chemical crosslinkers. Microstructural analysis revealed a porous, interconnected three-dimensional network favorable for the sustained release of bioactive factors. In a rat model of KOA, intra-articular administration of the AD-MSC supernatant-loaded hydrogel significantly improved joint architecture and locomotor performance, alleviated synovial inflammation, and preserved cartilage integrity. Radiographic and histological assessments demonstrated reduced cartilage degeneration and subchondral bone alterations. Moreover, the treatment markedly decreased intra-articular levels of proinflammatory cytokines (IL-1β and TNF-α) and the cartilage degradation marker CTX-II in a time-dependent manner. These findings indicated that the sustained local delivery of AD-MSC-derived supernatant effectively modulated joint inflammation and attenuated cartilage degeneration, with the hydrogel serving primarily as a delivery vehicle for these bioactive factors. This cell-free injectable biomaterial platform could offer a promising therapeutic strategy for the treatment of knee osteoarthritis. Full article

Background/Objectives: High-voltage, low-current electric shocks inflict superficial second-degree burns on the skin, accompanied by a vicious cycle of excessive oxidative stress and inflammation. As efficient treatment of such electrical burns remains a clinical challenge, we explored the efficacy of an injectable thermosensitive chitosan hydrogel engineered with an antioxidant agent (astaxanthin) and an anti-inflammatory agent (ibuprofen) for the treatment of high-voltage, low-current electrical burn injuries. Methods: The proposed CS/AST/IBU hydrogel was prepared and its thermosensitivity was characterized. Subsequently, the hydrogel was injected into the wounds of male Sprague–Dawley (SD) rats subjected to electrical burn injury (20 kV, 3 mA). Finally, a series of experiments were performed to elucidate the dynamics of wound healing and the mechanisms by which the hydrogel promotes wound repair. Results: The injectable hydrogel, through its thermally responsive gelation effect at 37 °C, adapts to the complex irregularities of the wound surface. This facilitates the release of astaxanthin and ibuprofen throughout the wound, which collectively diminish the formation of reactive oxygen species and MDA. Furthermore, it enhances the synthesis of endogenous antioxidants such as SOD, CAT, and GSH; encourages collagen deposition; stimulates the development of dermal appendages; and fosters neovascularization. It interrupts the deleterious cycle of oxidative stress and inflammation mediated by the NF-κB signaling pathway, thereby suppressing the expression of pro-inflammatory markers such as TNF-α, CD11b, and IL-1β while upregulating CD163, an anti-inflammatory receptor. Conclusions: The use of this multipronged, contour-adaptive hydrogel represents an effective strategy for complex wound management and demonstrates broad therapeutic potential for superficial second-degree electrical burns caused by high-voltage, low-current discharge. Full article

Bone regeneration focuses on the creation of functional tissue to repair bone defects. Creating a biodegradable scaffold hydrogel that combines a hemostatic agent with bioactive ceramics can afford the biological and mechanical benefits of both components. In the present study, we developed an injectable gelatin–alginate dual-composite hydrogel, loaded with two functional fillers: hydroxyapatite (HA) and the hemostatic agent montmorillonite (MMT). HA (microparticles and nanoparticles) was incorporated at concentrations of 10–30 mg/mL, with and without MMT at 20 mg/mL. The effects of functional fillers and their concentration on the microstructure and resulting physical and mechanical properties were studied, and a qualitative model summarising these effects was developed. All formulations exhibited clinically appropriate gelation times (5–29 s). n-HA significantly prolonged gelation time, reaching 29 ± 3 s at 30 mg/mL, while MMT reduced gelation time at all concentrations. The tensile strength of the unloaded hydrogel reached 20 kPa and increased to 57 kPa with 30 mg/mL of n-HA. The tensile strength even increased further with the addition of MMT (77 kPa). The results indicate that the combination of HA and MMT produced dual micro-composite hydrogels with moderate reinforcement, whereas the combination of n-HA and MMT generated dual nano–micro composites with combined reinforcing effects. The latter exhibited the highest strength and sealing ability while maintaining clinically relevant gelation times and controlled swelling behaviour. In conclusion, the combination of MMT with n-HA or HA enables the creation of functional hydrogels with controlled properties, tailored to specific applications in bone regeneration. Full article

Thermosensitive hydrogels have emerged as promising intelligent biomaterials for minimally invasive delivery and targeted therapy. Chitosan/gelatin thermosensitive hydrogels, integrating the biocompatibility, biodegradability, and antibacterial activity of chitosan with the excellent adhesive properties of gelatin, exhibit unique injectability, temperature-responsive gelation, and tunable physicochemical properties. This review systematically summarizes the key performance parameters of chitosan/gelatin thermosensitive hydrogels, including injectability, gelation characteristics (with sol-gel transition tunable between 37 and 42 °C to match diverse species’ body temperatures), mechanical properties, biocompatibility, degradation behavior (tunable from 1 to 8 weeks), drug-loading/release capabilities, and multi-stimuli responsiveness (pH/ROS/enzyme). It focuses on exploring their feasibility and suitability as acupoint embedding materials in Traditional Chinese Veterinary Medicine (TCVM), addressing the technical bottlenecks of traditional acupoint catgut embedding (e.g., unstable degradation, insufficient biocompatibility, and lack of drug-loading capacity). While recent studies have demonstrated the utility of such hydrogels in human disease models (e.g., rheumatoid arthritis and Parkinson’s disease), their translation to veterinary acupoint therapy remains largely unexplored. The prospective application of these hydrogels in treating common animal diseases (e.g., piglet diarrhea, canine degenerative joint disease, and equine laminitis) is, therefore, proposed and analyzed as an illustrative paradigm, emphasizing its integrated “stimulation–drug delivery” function and cross-species adaptability. Additionally, the current challenges (e.g., animal-specific formulation optimization, unclear mechanism of action, and insufficient long-term safety data) and future research directions (e.g., veterinary-specific formulation development, mechanistic exploration, and clinical translation) are highlighted. This review aims to promote the interdisciplinary integration of TCVM and smart biomaterials, provide precision strategies for animal disease treatment, and ultimately contribute to the modernization and standardization of TCVM technologies. Full article