Self-healing Hydrogels Research Articles

Formation of Zwitterionic and Self-Healable Hydrogels via Amino-yne Click Chemistry for Development of Cellular Scaffold and Tumor Spheroid Phantom for MRI.

In situ-forming biocompatible hydrogels have great potential in various medical applications. Here, we introduce a pH-responsive, self-healable, and biocompatible hydrogel for cell scaffolds and the development of a tumor spheroid phantom for magnetic resonance imaging. The hydrogel (pMAD) was synthesized via amino-yne click chemistry between poly(2-methacryloyloxyethyl phosphorylcholine-co-2-aminoethylmethacrylamide) and dialkyne polyethylene glycol. Rheology analysis, compressive mechanical testing, and gravimetric analysis were employed to investigate the gelation time, mechanical properties, equilibrium swelling, and degradability of pMAD hydrogels. The reversible enamine and imine bond mechanisms leading to the sol-to-gel transition in acidic conditions (pH ≤ 5) were observed. The pMAD hydrogel demonstrated potential as a cellular scaffold, exhibiting high viability and NIH-3T3 fibroblast cell encapsulation under mild conditions (37 °C, pH 7.4). Additionally, the pMAD hydrogel also demonstrated the capability for in vitro magnetic resonance imaging of glioblastoma tumor spheroids based on the chemical exchange saturation transfer effect. Given its advantages, the pMAD hydrogel emerges as a promising material for diverse biomedical applications, including cell carriers, bioimaging, and therapeutic agent delivery.

Cation-π Interaction-Enhanced Self-Healing Injectable Hydrogels for Gastric Perforation Repair.

Surgical operations are the preferred treatment for gastric perforation (GP) but incur postoperative complications such as gastrointestinal adhesions and bacterial infections, leading to inefficient wound healing and serious complications that may even threaten the life of the patient. Developing hydrogel dressings capable of adapting to the gastric environment (acid) and decreasing visceral adhesions and bacterial infections after GP treatment is crucial. In this article, we developed an injectable, self-healing hydrogel using cation-π interactions between protonated amines and aromatic rings under acidic conditions and explored it for GP repair. The hydrogels demonstrate exceptional self-healing capabilities under acidic conditions and can be effectively tailored for the gastric environment. In addition, the hydrogel demonstrated significant efficacy in preventing gastrointestinal adhesion, reducing inflammation, promoting angiogenesis, and effectively facilitating wound healing in a rat GP model. This novel hydrogel demonstrates adaptability to the gastric environment, rendering it highly promising for potential applications in gastric trauma healing.

Phytic Acid-Functional Cellulose Nanocrystals and Their Application in Self-Healing Nanocomposite Hydrogels.

Cellulose nanocrystals (CNCs) have garnered significant attention as a modifiable substrate because of their exceptional performances, including remarkable degradability, high tensile strength, high elastic modulus, and biocompatibility. In this article, the successful adsorption of phytic acid (PA) onto the surface of cellulose nanocrystals @polydopamine (CNC@PDA) was achieved. Taking inspiration from mussels, a dopamine self-polymerization reaction was employed to coat the surface of CNCs with PDA. Utilizing Pickering emulsion, the CNC@PDA-PA nanomaterial was obtained by grafting PA onto CNC@PDA. An environmentally friendly hydrogel was prepared through various reversible interactions using poly(acrylic acid) (PAA) and Fe3+ as raw materials with the assistance of CNC@PDA-PA. By multiple hydrogen bonding and metal-ligand coordination, nanocomposite hydrogels exhibit remarkable mechanical properties (the tensile strength and strain were 1.82 MPa and 442.1%, respectively) in addition to spectacular healing abilities (96.6% after 5 h). The study aimed to develop an innovative approach for fabricating nanocomposite hydrogels with exceptional self-healing capabilities.

Ultra-fast cryogenic self-healing ionic hydrogel for flexible wearable bioelectronics

Anti-freezing and self-healing hydrogels have been developed extensively for their irreplaceable advantages in flexible bioelectronics. However, the self-healing performance of hydrogels is extremely inefficient or even disappears in cryogenic environments, resulting in device damage and economic loss. Here, we proposed a ultra-fast cryogenic self-healing ionic hydrogel (ASCL) based on aldehyded hyaluronic acid (AHA) with the synergistic effect of dynamic Schiff base bonds and diselenide bonds. With the addition of lithium chloride (LiCl), the ASCL hydrogel can be rapidly self-healed within 5 min at a cryogenic temperature of −20 °C. The mechanism of LiCl for enhancing the anti-freezing property of hydrogels was demonstrated by molecular dynamics simulations and a series of tests at cryogenic temperatures. ASCL hydrogels exhibited good flexibility and high electrical conductivity of 0.27 S/m at cryogenic temperatures. The assembled ASCL hydrogel strain sensors and pressure sensors enable sensitive detection of various human motions at −20 °C, which possess a gauge factor of 1.07 and a sensing sensitivity of 0.29 kPa−1, respectively. This work provides a new paradigm for developing flexible wearable hydrogel bioelectronics in extreme environments.

Design of Cellulose Nanocrystal-Based Self-Healing Nanocomposite Hydrogels and Application in Motion Sensing and Sweat Detection.

Hydrogels, as flexible materials, have been widely used in the field of flexible sensors. Human sweat contains a variety of biomarkers that can reflect the physiological state of the human body. Therefore, it is of great practical significance and application value to realize the detection of sweat composition and combine it with human motion sensing through a hydrogel. Based on mussel-inspired chemistry, polydopamine (PDA) and gold nanoparticles (AuNPs) were coated on the surface of cellulose nanocrystals (CNCs) to obtain CNC-based nanocomposites (CNCs@PDA-Au), which could simultaneously enhance the mechanical, electrochemical, and self-healing properties of hydrogels. The CNCs@PDA-Au was composited with poly(vinyl alcohol) (PVA) hydrogel to obtain the nanocomposite hydrogel (PVA/CNCs@PDA-Au) by freeze-thaw cycles. The PVA/CNCs@PDA-Au has excellent mechanical strength (7.2 MPa) and self-healing properties (88.3%). The motion sensors designed with PVA/CNCs@PDA-Au exhibited a fast response time (122.9 ms), wide strain sensing range (0-600.0%), excellent stability, and fatigue resistance. With the unique electrochemical redox properties of uric acid, the designed hydrogel sensor successfully realized the detection of uric acid in sweat with a wide detection range (1.0-100.0 μmol/L) and low detection limit (0.42 μmol/L). In this study, the dual detection of human motion and uric acid in sweat was successfully realized by the designed PVA/CNCs@PDA-Au nanocomposite hydrogel.

Tailored Tough, Self-Healing, and Antimicrobial Double Cross-Linked Hydrogel Supercapacitor Electrodes with Excellent Capacitive Properties and Stable Conductivity

Tailored Tough, Self-Healing, and Antimicrobial Double Cross-Linked Hydrogel Supercapacitor Electrodes with Excellent Capacitive Properties and Stable Conductivity

Injectable Self-Healing Antibacterial Hydrogels with Tailored Functions by Loading Peptide Nanofiber-Biomimetic Silver Nanoparticles.

Polymer hydrogels find extensive application in biomedicine, serving specific purposes such as drug delivery, biosensing, bioimaging, cancer therapy, tissue engineering, and others. In response to the growing threat of bacterial infections and the escalating resistance to conventional antibiotics, this research introduces a novel injectable, self-healing antimicrobial hydrogel comprising bioactive aldolized hyaluronic acid (AHA) and quaternized chitosan (QCS). This designed QCS/AHA hydrogel incorporates self-assembling peptide nanofibers (PNFs) and small-sized silver nanoparticles (AgNPs) for tailored functionality. The resulting hybrid QCS/AHA/PNF/AgNPs hydrogel demonstrates impressive rheological characteristics, broad-spectrum antimicrobial efficacy, and high biocompatibility. Notably, its antimicrobial effectiveness against Escherichia coli and S. aureus surpasses 99.9%, underscoring its potential for treating infectious wounds. Moreover, the rheological analysis confirms its excellent shear-thinning and self-healing properties, enabling it to conform closely to irregular wound surfaces. Furthermore, the cytotoxicity assessment reveals its compatibility with human umbilical vein endothelial cells, exhibiting no significant adverse effects. The combined attributes of this bioactive QCS/AHA/PNF/AgNPs hydrogel position it as a promising candidate for antimicrobial applications and wound healing.

Self-Healing Dynamic Hydrogel Microparticles with Structural Color for Wound Management

HighlightsDerived from silica photonic crystals, inverse opal microspheres have a regularly connected porous structure and inherit structural color properties.Combined with the stable scaffold and the photothermal phase-transition of the secondary filling material, the inverse opal composite microspheres are endowed with self-healing properties and the ability for controllable drug release.Inverse opal microspheres were significantly treated for diabetic wound, via promoting tissue regeneration, collagen deposition and angiogenesis. Meanwhile, the release of drugs could be monitored by the structural color characteristic.

“All-in-one” self-healing and injectable cationic guar gum hydrogel dressing functionalized by bioactive complexes composed of natural small molecules

Reducing the risk of wound infection is an urgent issue health priority. Antibacterial polysaccharide-based hydrogels have attracted great attention for infectious wounds, attributed to their safe antimicrobial performance and natural non-toxicity and biodegradability advantages. In this study, the “all-in-one” self-adaptive and injectable cationic guar gum (CG)-based polysaccharide hydrogels (FA-TOB/CG) loaded with bioactive complexes were developed for infectious wound healing. The constructed antioxidant and antibacterial ferulic acid (FA)-tobramycin (TOB) bioactive complexes (FA-TOB) were used as the cross-linking agent and introduced into the CG matrix to construct the FA-TOB/CG hydrogel with a three-dimensional porous structure. The sterilization rates of FA-TOB/CG hydrogel against S. aureus and E. coli reached 98 % and 80 % respectively. In addition, the FA-TOB/CG also exhibits enhanced antioxidant performances (DPPH: > 40 %; ABTS: > 90 %; ·OH: > 50 %). More importantly, FA-TOB/CG hydrogel also showed the ability to sustain the release of FA and TOB. These superiorities of the FA-TOB/CG hydrogel enabled it to provide a moist wound environment and promote wound healing by eliminating bacteria, modulating the local inflammatory response, and accelerating collagen deposition and vascular regeneration. Thus, this study may enlarge a new sight for developing multifunctional dressings by incorporating bioactive complexes into polysaccharide hydrogels for infected wounds.

Surface functionalization of cellulose nanocrystals for fabricating of anti-freezing and self-healing nanocomposites hydrogels

In recent years, biomass-based self-healing hydrogels have shown great potential, but are incredibly prone to freezing at low temperature. It is therefore essential to develop hydrogels with excellent frost resistance. In this work, cellulose nanocrystalline functional nanomaterials (CNC-g-GB) were successfully prepared by grafting betaine hydrochloride (GB-HCl) onto cellulose nanocrystals (CNCs) surface in an environmentally friendly deep eutectic solvent (BhG DES) through esterification. Self-healing hydrogels with antifreeze properties were prepared by a one-pot method using amphoteric guar gum (AGG) and poly (acrylic acid) (PAA) as hydrogel matrix and Fe(Ⅲ) as cross-linking agent. The hydrogel was named AGG/CNC-g-GB hydrogel. Due to the intense hydration of cations and anions in AGG and the metal coordination of Fe(Ⅲ) with the hydrogel network, the hydrogel has pretty freezing resistance (−20.0 °C) and self-healing rate (86.0%). It provides new ideas for developing hydrogels with enhanced cold resistance and self-healing properties.

Innovative Use of an Injectable, Self-Healing Drug-Loaded Pectin-Based Hydrogel for Micro- and Supermicro-Vascular Anastomoses.

Microvascular surgery plays a crucial role in reconnecting micrometer-scale vessel ends. Suturing remains the gold standard technique for small vessels; however, suturing the collapsed lumen of microvessels is challenging and time-consuming, with the risk of misplaced sutures leading to failure. Although multiple solutions have been reported, the emphasis has predominantly been on resolving challenges related to arteries rather than veins, and none has proven superior. In this study, we introduce an innovative solution to address these challenges through the development of an injectable lidocaine-loaded pectin hydrogel by using computational and experimental methods. To understand the extent of interactions between the drug and the pectin chain, molecular dynamics (MD) simulations and quantum mechanics (QM) calculations were conducted in the first step of the research. Then, a series of experimental studies were designed to prepare lidocaine-loaded injectable pectin-based hydrogels, and their characterization was performed by using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and rheological analysis. After all the results were evaluated, the drug-loaded pectin-based hydrogel exhibiting self-healing properties was selected as a potential candidate for in vivo studies to determine its performance during operation. In this context, the hydrogel was injected into the divided vessel ends and perivascular area, allowing for direct suturing through the gel matrix. While our hydrogel effectively prevented vasospasm and facilitated micro- and supermicro-vascular anastomoses, it was noted that it did not cause significant changes in late-stage imaging and histopathological analysis up to 6 months. We strongly believe that pectin-based hydrogel potentially enhanced microlevel arterial, lymphatic, and particularly venous anastomoses.

Ultrafast gelation of multifunctional β-cyclodextrin based hydrogel electrolyte for self-healing supercapacitor

The increasing attention towards flexible supercapacitors with self-healing ability can be attributed to their capacity to endure deformation and damage. However, the development of self-healing and adhesive hydrogel electrolytes, which serve as substrate materials for supercapacitors, remains a challenge. This work reports an ultrafast gelation method for fabricating multifunctional PAA-SL-CD hydrogels with ultrahigh stretchability, fast self-healing ability, superior adhesion, and high ionic conductivity (6.15 S/m). These excellent properties can be attributed to the hydrogen bonding between β-CD, the catechol groups and PAA chains, as well as metal-catechol coordination, metal-carboxyl coordination, and the unique truncated cone structure of the β-CD molecule. A flexible supercapacitor, fabricated using PAA-SL-CD hydrogel as electrolyte, demonstrates high areal specific capacitance (950 mF/cm2) and a capacitance retention rate of 76.3 % even after five cutting and healing cycles. With the well-designed adhesion of the hydrogel electrolyte, the device exhibits impressive specific capacitance retention after cyclic bending. Notably, a series supercapacitor retains the ability to power a clock for 28 min.

Resilient 3D porous self-healable triple network hydrogels reinforced with graphene oxide for high-performance flexible supercapacitors

The application of gel polymer electrolyte (GPE) in flexible supercapacitor (FSC) has attracted much attention due to its excellent mechanical properties and chemical stability. However, traditional polymer substrates have high crystallinity, resulting in sluggish ion migration and low ionic conductivity. This study reports the successful fabrication of a resilient highly porous triple hydrogel network (TNH) comprising the natural polymer of sodium alginate and biocompatible components of polyvinyl alcohol and graphene oxide (GO), exhibiting remarkably high ionic conductivity and astonishing mechanical strength, self-healing, and flame retardant properties. The physical and electrochemical features of the GPEs were optimized by tuning the GO wt% within the polymeric matrix. Adding a low wt% of GO (0.8 wt%) led to remarkable improvements in ionic conductivity (83.33 mS cm−1), mechanical strength (2.21 MPa), and self-healing and flame-retardant properties of the resulting PVA/SA/GO GPE than the pristine GPE. This was attributed to the formation of a microporous three-dimensional polymeric network based on reversible non-covalent bonds. The carbon cloth-based symmetric SC prepared based on this GPE exhibited a long cycle life, high specific capacitance of 633.3 mF cm−2 at 0.5 mA cm−2, and an energy density of 84 mWh cm−2 at a high power density of 500.2 mW cm−2 (at 1 mA cm−2)), which surpassed the values reported in previous studies. The electrochemical performance of the FSC prepared based on PVA/SA/GO GPE remained constant when subjected to bending deformation, indicating the harmonious physical, chemical, and electrochemical properties of the developed GPE and its suitability for flexible energy storage devices, and wearable electronics

Investigating Temperature-Dependent Microscopic Deformation in Tough and Self-Healing Hydrogel Using Time-Resolved USAXS.

Tough and self-healing hydrogels are typically sensitive to loading rates or temperatures due to the dynamic nature of noncovalent bonds. Understanding the structure evolution under varying loading conditions can provide valuable insights for developing new tough soft materials. In this study, polyampholyte (PA) hydrogel with a hierarchical structure is used as a model system. The evolution of the microscopic structure during loading is investigated under varied loading temperatures. By combining ultra-small angle X-ray scattering (USAXS) and Mooney-Rivlin analysis, it is elucidated that the deformation of bicontinuous hard/soft phase networks is closely correlated with the relaxation dynamics or strength of noncovalent bonds. At high loading temperatures, the gel is soft and ductile, and large affine deformation of the phase-separated networks is observed, correlated with the fast relaxation dynamics of noncovalent bonds. At low loading temperatures, the gel is stiff, and nonaffine deformation occurs from the onset of loading due to the substantial breaking of noncovalent bonds and limited chain mobility as well as weak adaptation of phase deformation to external stretch. This work provides an in-depth understanding of the relationship between structure and performance of tough and self-healing hydrogels.

Mucus-Inspired Self-Healing Hydrogels: A Protective Barrier for Cells against Viral Infection.

Mucus is a dynamic biological hydrogel, composed primarily of the glycoprotein mucin, exhibits unique biophysical properties and forms a barrier protecting cells against a broad-spectrum of viruses. Here, this work develops a polyglycerol sulfate-based dendronized mucin-inspired copolymer (MICP-1) with ≈10% repeating units of activated disulfide as cross-linking sites. Cryo-electron microscopy (Cryo-EM)analysis of MICP-1 reveals an elongated single-chain fiber morphology. MICP-1 shows potential inhibitory activity against many viruses such as herpes simplex virus 1 (HSV-1) and SARS-CoV-2 (including variants such as Delta and Omicron). MICP-1 produces hydrogels with viscoelastic properties similar to healthy human sputum and with tuneable microstructures using linear and branched polyethylene glycol-thiol (PEG-thiol) as cross-linkers. Single particle tracking microrheology, electron paramagnetic resonance (EPR) and cryo-scanning electron microscopy (Cryo-SEM) are used to characterize the network structures. The synthesized hydrogels exhibit self-healing properties, along with viscoelastic properties that are tuneable through reduction. A transwell assay is used to investigate the hydrogel's protective properties against viral infection against HSV-1. Live-cell microscopy confirms that these hydrogels can protect underlying cells from infection by trapping the virus, due to both network morphology and anionic multivalent effects. Overall, this novel mucin-inspired copolymer generates mucus-mimetic hydrogels on a multi-gram scale. These hydrogels can be used as models for disulfide-rich airway mucus research, and as biomaterials.

Self-Healing Conductive Hydrogels with Dynamic Dual Network Structure Accelerate Infected Wound Healing via Photothermal Antimicrobial and Regulating Inflammatory Response.

Wound infections are an escalating clinical challenge with continuous inflammatory response and the threat of drug-resistant bacteria. Herein, a series of self-healing conductive hydrogels were designed based on carboxymethyl chitosan/oxidized sodium alginate/polymerized gallic acid/Fe3+ (CMC/OSA/pGA/Fe3+, COGFe) for promoting infected wound healing. The Schiff base and catechol-Fe3+ chelation in the dynamical dual network structure of the hydrogels endowed dressings with good toughness, conductivity, adhesion, and self-healing properties, thus flexibly adapting to the deformation of skin wounds. In terms of ultraviolet (UV) resistance and scavenging of reactive oxygen species (ROS), the hydrogels significantly reduced oxidative stress at the wound site. Additionally, the hydrogels with photothermal therapy (PTT) achieved a 95% bactericidal rate in 5 min of near-infrared (NIR) light radiation by disrupting the bacterial cell membrane structure through elevated temperature. Meanwhile, the inherent antimicrobial properties of GA could reduce healthy tissue damage caused by excessive heat. The composite hydrogels could effectively promote the proliferation and migration of fibroblasts and possess good biocompatibility and hemostatic effect. In full-thickness infected wound repair experiments in rats, the COGFe5 hydrogel combined with NIR effectively killed bacteria, modulated macrophage polarization (M1 to M2 phenotype) to improve the immune microenvironment of the wound, and shortened the repair time by accelerating the expression of collagen deposition (TGF-β) and vascular factors (CD31). This combined therapy might provide a prospective strategy for infectious wound treatment.

Fabrication of a self-healing hydrogel with antibacterial activity using host-guest interactions between dopamine-modified alginate and β-cyclodextrin dimer

Self-healing hydrogels possess an ability to recover their functionality after experiencing damage by regenerating cross-links. The main challenge in making self-healing hydrogels based on host-guest (HG) interactions is their limited mechanical strength, which can be solved using beta-cyclodextrin dimers (β-CDsD). Here, β-CDsD as a host cross-linker was used to increase the mechanical property of the HG interactions. Alginate with acceptable biocompatibility was modified by dopamine (ALG-DOP) and employed as a guest polymer. Self-healing hydrogel was developed between them, and Ag nanoparticles were added to create an antibacterial activity. Dopamine with appropriate size and suitable adhesiveness established HG interactions with β-CDsD, and cells were able to grow well on hydrogel. This hydrogel showed an impressive self-healing capability <5 min. These hydrogels revealed a respectable porosity from 15 to 55 μm essential for exchanging the substances required for cell growth and cell waste elimination. Biocompatibility was investigated against NIH 3 T3 fibroblasts cells, and the results showed that the cells grew well. The in vitro release of curcumin from the hydrogel was examined in PBS at pH of 7.4. The hydrogel can be a perfect candidate for controlled drug release, and wound-dressing due to self-healing property, antibacterial activity, adhesion, and biocompatibility.

Injectable hydrogel based on liposome self-assembly for controlled release of small hydrophilic molecules

Controlled release of low molecular weight hydrophilic drugs, administered locally, allows maintenance of high concentrations at the target site, reduces systemic side effects, and improves patient compliance. Injectable hydrogels are commonly used as a vehicle. However, slow release of low molecular weight hydrophilic drugs is very difficult to achieve, mainly due to a rapid diffusion of the drug out of the drug delivery system. Here we present an injectable and self-healing hydrogel based entirely on the self-assembly of liposomes. Gelation of liposomes, without damaging their structural integrity, was induced by modifying the cholesterol content and surface charge. The small hydrophilic molecule, sodium fluorescein, was loaded either within the extra-liposomal space or encapsulated into the aqueous cores of the liposomes. This encapsulation strategy enabled the achievement of controlled and adjustable release profiles, dependent on the mechanical strength of the gel. The hydrogel had a high mechanical strength, minimal swelling, and slow degradation. The liposome-based hydrogel had prolonged mechanical stability in vivo with benign tissue reaction. This work presents a new class of injectable hydrogel that holds promise as a versatile drug delivery system. Statement of significanceThe porous nature of hydrogels poses a challenge for delivering small hydrophilic drug, often resulting in initial burst release and shorten duration of release. This issue is particularly pronounced with physically crosslinked hydrogels, since their matrix can swell and dissipate rapidly, but even in cases where the polymers in the hydrogel are covalently cross-linked, small molecules can be rapidly released through its porous mesh. Here we present an injectable self-healing hydrogel based entirely on the self-assembly of liposomes. Small hydrophilic molecules were entrapped inside the extra-liposomal space or loaded into the aqueous cores of the liposomes, allowing controlled and tunable release profiles.

Self-healing hydrogel prepared from gallic acid coupled P(NIPAM-co-AH) and oxidized sodium alginate for diabetic wound repairing

Due to the complex wound microenvironment, diabetic wound repairing remains as an important clinical problem caused by excessive ROS, bacterial infection and persistent inflammation. In this study, gallic acid (GA) was grafted onto the P(NIPAM-co-AH) copolymers to synthesize functional copolymer with hydrazide functional group and GA moiety (PNHG). Then the PNHG was cross-linked by sodium alginate oxide (OSA) to fabricate self-healing hydrogel with multifunctionalility of tissue adhesion, ROS scavenging, biodegradability and antibacterial property. The multifunctional hydrogel showed expected advantages proved the GA enhanced the ROS scavenging property, tissue adhesion and antibacterial activity. Moreover, the hydrogel preserved the biocompatibility and the biodegradability of the precursors. Furthermore, the multifunctional hydrogel showed improved hemostatic property and greatly promoted repairing rate of diabetic wounds on mice model in vivo. In conclusion, this multifunctional PNHG/OSA hydrogel can play a important role as wound dressing in the future.

Dynamic hydrogel–metal–organic framework system promotes bone regeneration in periodontitis through controlled drug delivery

Periodontitis is a prevalent chronic inflammatory disease, which leads to gradual degradation of alveolar bone. The challenges persist in achieving effective alveolar bone repair due to the unique bacterial microenvironment’s impact on immune responses. This study explores a novel approach utilizing Metal–Organic Frameworks (MOFs) (comprising magnesium and gallic acid) for promoting bone regeneration in periodontitis, which focuses on the physiological roles of magnesium ions in bone repair and gallic acid's antioxidant and immunomodulatory properties. However, the dynamic oral environment and irregular periodontal pockets pose challenges for sustained drug delivery. A smart responsive hydrogel system, integrating Carboxymethyl Chitosan (CMCS), Dextran (DEX) and 4-formylphenylboronic acid (4-FPBA) was designed to address this problem. The injectable self-healing hydrogel forms a dual-crosslinked network, incorporating the MOF and rendering its on-demand release sensitive to reactive oxygen species (ROS) levels and pH levels of periodontitis. We seek to analyze the hydrogel’s synergistic effects with MOFs in antibacterial functions, immunomodulation and promotion of bone regeneration in periodontitis. In vivo and in vitro experiment validated the system's efficacy in inhibiting inflammation-related genes and proteins expression to foster periodontal bone regeneration. This dynamic hydrogel system with MOFs, shows promise as a potential therapeutic avenue for addressing the challenges in bone regeneration in periodontitis.Graphical