An Injectable Chitosan-Based Self-Healable Hydrogel System as an Antibacterial Wound Dressing.

Due to the lack of efficient bioelectronic interfaces, the communication between biology and electronics has become a great challenge, especially in constructing bioelectronic sensing. As natural polysaccharide biomaterials, chitosan-based hydrogels exhibit the advantages of flexibility, biocompatibility, mechanical tunability, and stimuli sensitivity, and could serve as an excellent interface for bioelectronic sensors. Based on the fabrication approaches, interaction mechanisms, and bioelectronic communication modalities, this review divided chitosan-based hydrogels into four types, including electrode-based hydrogels, conductive materials conjugated hydrogels, ionically conductive hydrogels, and redox-based hydrogels. To introduce the enhanced performance of bioelectronic sensors, as a complementary alternative, the incorporation of nanoparticles and redox species in chitosan-based hydrogels was discussed. In addition, the multifunctional properties of chitosan-based composite hydrogels enable their applications in biomedicine (e.g., smart skin patches, wood healing, disease diagnosis) and food safety (e.g., electrochemical sensing, smart sensing, artificial bioelectronic tongue, fluorescence sensors, surface-enhanced Raman scattering). We believe that this review will shed light on the future development of chitosan-based biosensing hydrogels for micro-implantable devices and human-machine interactions, as well as potential applications in medicine, food, agriculture, and other fields.

Biocompatible chitosan-based hydrogels have attracted extensive attention in wound dressing due to their human skin-like tissue characteristics. However, it is a crucial challenge to fabricate chitosan-based hydrogels with versatile properties, including flexibility, stretchability, adhesivity, and antibacterial activity. In this work, a kind of chitosan-based hydrogels with integrated functionalities are facilely prepared by solution polymerization of acrylamide (AAm) and sodium p-styrene sulfonate (SS) in the presence of quaternized carboxymethyl chitosan (QCMCS). Due to the dual cross-linking between QCMCS and P(AAm-co-SS), the optimized QCMCS/P(AAm-co-SS) hydrogel exhibits tough mechanical properties (0.767MPa tensile stress and 1100% fracture strain) and moderate tissue adhesion (11.4kPa). Moreover, biological evaluation in vitro illustrated that as-prepared hydrogel possesses satisfactory biocompatibility, hemocompatibility, and excellent antibacterial ability (against S. aureus and E. coli are 98.8% and 97.3%, respectively). Then, the hydrogels are tested in a rat model for bacterial infection incision in vivo, and the results show that they can significantly accelerate epidermal regeneration and wound closure. This is due to their ability to reduce the inflammatory response, promote the formation of collagen deposition and granulation tissue. The proposed chitosan-based antibacterial hydrogels have the potential to be a highly effective wound dressing in clinical wound healing.

Chitosan-based injectable hydrogel with multifunction for wound healing: A critical review

Construction of chitosan-based thermosensitive composite hydrogels for recognizing and combined chemo-photodynamic elimination of Gram-negative bacterial infections

The effect of two crosslink strategies on the preparation of chitosan-based covalent hydrogels was investigated employing the widely used thiol-ene reaction. This versatile “click” chemistry can be activated either photochemically or thermochemically. Initially, well-purified chitosan (CS, DA ∼4 %, Mw ∼580 kg mol−1) was separately functionalized with vinyl (CS-ene) or thiol (CS-SH) groups in aqueous media. Subsequently, two strategies were compared where thiol-ene reaction occurs respectively between: (S1) modified chitosans CS-ene and CS-SH, in a polymer – polymer strategy, and (S2) CS-ene and di(ethylene glycol) dithiol (dEG-(SH)2), in a polymer – molecule strategy.Both crosslinking strategies were evaluated through rheological measurements, starting with entangled chitosan solutions. The difference in diffusion of functional groups, whether attached to polymer chains or to free molecules, leads to faster gelation kinetics with S2. Consequently, stronger gels were obtained with S2, where the modulus was connected with the degree of functionalization, while S1 produced weaker gels closer to the percolation point, where crosslinked density was associated with the entanglement number derived from the initial concentration. Nevertheless, networks formed by both strategies were homogenous with minimal dissipative contributions to their rheological properties, indicating that structural defects are negligible.

The presence of bacteria directly affects wound healing. Chitosan-based hydrogel biomaterials are a solution as they offer advantages for wound-healing applications due to their strong antimicrobial properties. Here, a double-cross-linking chitosan-based hydrogel with antibacterial, self-healing, and injectable properties is reported. Thiolated chitosan was successfully prepared, and the thiolated chitosan molecules were cross-linked by Ag–S coordination to form a supramolecular hydrogel. Subsequently, the amine groups in the thiolated chitosan covalently cross-linked with genipin to further promote hydrogel formation. In vitro experimental results indicate that hydrogel can release Ag+ over an extended time, achieving an antibacterial rate of over 99% against Escherichia coli and Staphylococcus aureus. Due to the reversible and dynamic feature of Ag–S coordination, an antibacterial hydrogel exhibited injectable and self-healing capabilities. Additionally, the hydrogel showed excellent biocompatibility and biodegradability.

The recent advancement in the chitosan-based thermosensitive hydrogel for tissue regeneration

Progress in preparation and properties of chitosan-based hydrogels

Chitosan nanoparticles can be used in many types of applications such as food packaging, cosmetics and biomedical field. Chitosan can be modified to form chitosan-based hydrogels for antiviral purpose. Chitosan-based hydrogels are commonly used in wound healing, tissue engineering and drug delivery. This study explains about the properties and the applications of chitosan-based hydrogels since there were not much paper or research about chitosan-based hydrogels used as antiviral agent. Usually, many researchers did some studies about antiviral application focusing only on chitosan itself but not specifically into chitosan-based hydrogels. The properties of chitosan are also not well explained in some research. The purpose of this study is to investigate the antiviral application of chitosan-based hydrogels based on chitosan properties.

Thermoresponsive dual-network chitosan-based hydrogels with demineralized bone matrix for controlled release of rhBMP9 in the treatment of femoral head osteonecrosis.

Chitosan-based high-strength supramolecular hydrogels for 3D bioprinting

Diabetic foot ulcers (DFUs) are a multifactorial medical problem that require multifaceted approaches for effective healing. Most research on DFU healing has concentrated on promoting wound closure, with less emphasis on the quality of repaired tissue. This is problematic, however, since quality of the repaired tissues can have potential to improve wound healing outcomes and limit re-ulceration. If more functionally active dermis replaces the lost tissue, this can effectively maximize strength, organization, and overall structure of the plantar surface. Additionally, DFUs commonly show multi-strain infection, which further exacerbates the non-healing status of these wounds. Treatment of chronic wounds can be benefitted by application of oxygen and localized infection treatment, both can be achieved via our methacrylated chitosan-based (MACF) hydrogel. A non-healing diabetic infected wound model was used to explore extracellular matrix (ECM) organization, tensile strength, and metabolomic profiles at a 21-day endpoint as a marker for maturation and improved functionality of repaired tissues over normal scar formation. Effective remediation of infection was achieved with 14 days of polyhexamethylene biguanide (PHMB) application with improved wound repair compared to continuous treatment. Prolonged (21 day) application of PHMB showed resulting necrosis, although standard application times for patients with infected wounds can reach up to 28 continuous days. Biaxial mechanical analysis showed improved isotropic strength of infected tissues treated with MACF with PHMB stopped on D14, supported by collagen fiber orientation in second harmonics generation (SHG) imaging. Oxygenating MACF treatments also improved collagen deposition through the enhancement of the hydroxyproline fibrillary collagen synthesis pathway. These structural and mechanical results demonstrate a promising potential treatment for infected diabetic foot ulcers which shows improved dermal functionality. STATEMENT OF SIGNIFICANCE: Diabetic foot ulcers are a multifaceted problem in the medical field exacerbated by infection, with potential for gangrene, lower limb amputation, sepsis, or death. Current treatment regimens include oxygen therapy, physical debridement, and strong antibacterials. However, there is a lack of multi-faceted approaches, which we have designed in our oxygenating chitosan-based hydrogels capable of delivering antibiotics. Treatments currently focus on closure of wounds; however, functionality of regenerated tissues are limited due to fibrotic scar formation. Therefore, we have chosen to focus not only on closure, but also quality of regenerated tissues through mechanical testing and analysis of extracellular matrix composition and organization, with a goal of improving functionality of regenerated tissues.

Chitosan-based self-healing hydrogel dressing for wound healing

Effective wound healing hinges on a precisely orchestrated tissue remodeling process that restores both structural integrity and functionality. This review delineates the molecular mechanisms by which chitosan-based hydrogels revolutionize wound repair. Derived from natural chitin, chitosan uniquely combines robust antimicrobial, hemostatic, and biodegradable properties with the capacity to modulate critical intracellular signaling cascades-including transforming growth factor-β, mitogen-activated protein kinase, and PI3K/AKT. These dynamic interactions drive fibroblast proliferation, stimulate the strategic transition from type III to type I collagen deposition, and finely tune extracellular matrix reorganization, thereby mitigating excessive fibrosis and minimizing scar formation. Notwithstanding its considerable therapeutic promise, clinical translation of chitosan-based hydrogels is tempered by challenges in mechanical stability and controlled degradation. We propose that advanced material engineering-encompassing precision cross-linking, nanoparticle integration, and synergistic stem cell-based strategies-could surmount these limitations. This comprehensive synthesis of current molecular insights sets the stage for next-generation regenerative biomaterials, positioning chitosan-based hydrogels as a paradigm-shifting platform for achieving superior healing outcomes in complex clinical scenarios.

The prospective applications of chitosan-based hydrogels (CBHs), a category of biocompatible and biodegradable materials, in biomedical disciplines such as tissue engineering, wound healing, drug delivery, and biosensing have garnered great interest. The synthesis and characterization processes used to create CBHs play a significant role in determining their characteristics and effectiveness. The qualities of CBHs might be greatly influenced by tailoring the manufacturing method to get certain traits, including porosity, swelling, mechanical strength, and bioactivity. Additionally, characterization methods aid in gaining access to the microstructures and properties of CBHs. Herein, this review provides a comprehensive assessment of the state-of-the-art with a focus on the affiliation between particular properties and domains in biomedicine. Moreover, this review highlights the beneficial properties and wide application of stimuli-responsive CBHs. The main obstacles and prospects for the future of CBH development for biomedical applications are also covered in this review.