Construction of an Injectable Composite Double-Network Hydrogel as a Liquid Embolic Agent.

Conventional embolists disreputably tend to recanalization arising from the low filling ratio due to their rigidity or instability. As a result, intelligent hydrogels with a tunable modulus may meaningfully improve the therapeutic efficacy. Herein, an injectable composite double-network (CDN) hydrogel with high shear responsibility was prepared as a liquid embolic agent by cross-linking poly(vinyl alcohol) (PVA) and carboxymethyl chitosan (CMC) via dynamic covalent bonding of borate ester and benzoic-imine. A two-dimensional nanosheet, i.e., layered double hydroxide (LDH), was incorporated into the network through physical interactions which led to serious reduction of yield stress for the injection of the hydrogel and the capacity for loading therapeutic agents like indocyanine green (ICG) and doxorubicin (DOX) for the functions of photothermal therapy (PTT) and chemotherapy. The CDN hydrogel could thus be transported through a thin catheter and further in situ strengthened under physiological conditions, like in blood, by secondarily cross-linking with phosphate ions for longer degradation duration and better mechanical property. These characteristics met the requirements of arterial interventional embolization, which was demonstrated by renal embolism operation on rabbits, and meanwhile favored the inhibition of subcutaneous tumor growth on an animal model. Therefore, this work makes a breakthrough in the case of largely reducing the embolism risks, thus affording a novel generation for interventional embolization.

Polymer-Protein Assemblies with Tunable Vesicular and Hierarchical Nanostructures.

The construction of variable structured multi-protein nano-assemblies is of great interest for the development of protein-based therapeutic systems. This study showcases the synthesis of polymer-protein assemblies with tunable structure like single- and multi-layer polymer-crosslinked protein vesicles, Janus protein vesicles and other hierarchical-structured assemblies by utilizing a dynamic template-assistant intermittent-assembly approach. The generalization of the methodology helps the protein assemblies to gain notable functional complexity. And we demonstrate compelling evidence highlighting the substantial impact of the topological morphology of protein nanoaggregates on their cellular uptake capacity.

Oxygen and pH responsive theragnostic liposomes for early-stage diagnosis and photothermal therapy of solid tumours.

The development of cancer treatment is of great importance, especially in the early stage. In this work, we synthesized a pH-sensitive amphiphilic ruthenium complex containing two alkyl chains and two PEG chains, which was utilized as an oxygen sensitive fluorescent probe for co-assembly with lipids to harvest a liposomal delivery system (RuPC) for the encapsulation of a photothermal agent indocyanine green (ICG). The resultant ICG encapsulated liposome (RuPC@ICG) enabled the delivery of ICG into cells via a membrane fusion pathway, by which the ruthenium complex was localized in the cell membrane for better detection of the extracellular oxygen concentration. Such characteristics allowed ratiometric imaging to distinguish the tumour location from normal tissues just 3 days after cancer cells were implanted, by monitoring the hypoxia condition and tracing the metabolism. Moreover, the pH sensitivity of the liposomes favoured cell uptake, and improved the anti-tumour efficiency of the formulation in vivo under NIR irradiation. Assuming liposomal systems have fewer safety issues, our work not only provides a facile method for the construction of a theragnostic system by combining phototherapy with photoluminescence imaging, but hopefully paves the way for clinical translation from bench to bedside.

Construction of Processable Ultrastiff Hydrogel for Periarticular Fracture Strutting and Healing.

Development of bioactive bone and joint implants that offer superior mechanical properties to facilitate personalized surgical procedures remains challenging in the field of biomedical materials. As for the hydrogel, mechanical property and processability are major obstructions hampering its application as load-bearing scaffolds in orthopedics. Herein, we constructed implantable composite hydrogels with appealing processability and ultrahigh stiffness. Central to our design is the incorporation of a thixotropic composite network into an elastic polymer network via dynamic interactions to synthesize a percolation-structured double-network (DN) hydrogel with plasticity, followed by in situ strengthening and self-strengthening mechanisms for fostering the DN structure to the cojoined-network structure and subsequently mineralized-composite-network structure to harvest excellent stiffness. The ultrastiff hydrogel is shapeable and can reach a compressive modulus of 80-200 MPa together with a fracture energy of 6-10 MJ/m3, comparable to the mechanical performance of cancellous bone. Moreover, the hydrogel is cytocompatible, osteogenic, and showed almost no volume shrinkage within 28 days in simulated body fluid or culture medium. Such characteristics enabled the utility of a hydrogel in the reduction and stabilization of periarticular fracture treatment on a distal femoral AO/OTA B1 fracture rabbit model and successfully avoided the recollapse of the articular surface.

Effect of Dl-3-n-butylphthalide on mitochondrial Cox7c in models of cerebral ischemia/reperfusion injury.

Several studies have demonstrated the protective effect of dl-3-n-Butylphthalide (NBP) against cerebral ischemia, which may be related to the attenuation of mitochondrial dysfunction. However, the specific mechanism and targets of NBP in cerebral ischemia/reperfusion remains unclear. In this study, we used a chemical proteomics approach to search for targets of NBP and identified cytochrome C oxidase 7c (Cox7c) as a key interacting target of NBP. Our findings indicated that NBP inhibits mitochondrial apoptosis and reactive oxygen species (ROS) release and increases ATP production through upregulation of Cox7c. Subsequently, mitochondrial respiratory capacity was improved and the HIF-1α/VEGF pathway was upregulated, which contributed to the maintenance of mitochondrial membrane potential and blood brain barrier integrity and promoting angiogenesis. Therefore, our findings provided a novel insight into the mechanisms underlying the neuroprotective effects of NBP, and also proposed for the first time that Cox7c exerts a critical role by protecting mitochondrial function.

Injectable Double-Network Hydrogel-Based Three-Dimensional Cell Culture Systems for Regenerating Dental Pulp.

The regeneration of dental pulp tissue is very important, but difficult, in dentistry. The biocompatibility, water content, and viscoelastic properties of pulp-like tissue must be optimized to achieve the efficient transfer of metabolites and nutrients, a suitable degradation rate, distribution of encapsulated cells, injectability, and gelation in situ under physiological conditions. As promising materials for pulp regeneration, hydrogel scaffolds have been produced to simulate the extracellular matrix and transmit signaling molecules. It is imperative to develop hydrogels to effectively regenerate pulp tissue for clinical application. Here, two injectable double-network (DN) hydrogel-based three-dimensional (3D) cell culture systems were developed for regenerating dental pulp. The microstructure, mechanical property, rheology property, and degradation behavior of the injectable DN glycol chitosan-based hydrogels in a simulated root canal model were characterized and compared to a single-network (SN) glycol chitosan-based hydrogel. Human dental pulp stem cells (hDPSCs) were then encapsulated into the GC-based hydrogels for the regeneration of pulp tissue, and the biological performance was investigated both in vitro and in vivo. The results showed that the DN hydrogels had ideal injectability under physiological conditions due to the dynamic nature of the crosslinks. Besides, the DN hydrogels exhibited better mechanical properties and longer degradation duration than the corresponding SN hydrogel. As a 3D cell culture system, the characteristics of the DN hydrogel facilitated odontogenic differentiation and mineralization of hDPSCs in vitro. Further in vivo analysis confirmed that the chemical composition, matrix stiffness, and degradation rate of the DN hydrogel matched those of pulp-like fibrous connective tissue, which might be related to Smad3 activation. These findings demonstrate that DN glycol chitosan-based hydrogels are suitable for the regeneration of pulp tissue.

Layered double hydroxide-based nanozyme for NO-boost multi-enzyme dynamic therapy with tumor specificity.

The development of dual chemodynamic therapy and NO therapy can significantly improve the efficiency of cancer treatment. Therefore, designing a multifunctional agent to take full advantage of them and maximize their therapeutic effect remains a challenging goal. Herein, we have developed a novel LDHzyme by the confinement of L-arginine (L-Arg) on the surface of Mn-LDH nanosheets. The LDHzyme can exhibit multiple enzyme-like catalytic activities, including peroxidase (POD), oxidase (OXD), and nitric oxide synthase (iNOS). Based on these enzyme-mimicking properties, LDHzyme possesses significant catalytic efficiency with a high maximum velocity of 1.41 × 10-6 M s-1, which is higher than the majority of other nanozymes. In addition, this LDHzyme can exhibit outstanding NO-enhanced lethality of ROS and further improve its efficacy. The therapeutic effect of LDHzyme has been verified to significantly inhibit tumor growth in HeLa xenograft Balb/c nude mice models, as demonstrated in both in vitro and in vivo models, revealing the promising prospects of NO-enhanced multi-enzyme dynamic therapy (MDT). These results open up an opportunity to enable the utilization of an LDH-based nanozyme as a curative nanosystem to inhibit tumor growth.

Microcirculation No-Reflow Phenomenon after Acute Ischemic Stroke.

BACKGROUND: The no-reflow phenomenon refers to a failure to restore normal cerebral microcirculation despite brain large artery recanalization after acute ischemic stroke, which was observed over 50 years ago. SUMMARY: Different mechanisms contributing to no-reflow extend across the endovascular, vascular wall, and extravascular factors. There are some clinical tools to evaluate cerebral microvascular hemodynamics and represent biomarkers of the no-reflow phenomenon. As substantial experimental and clinical data showed that clinical outcome was better correlated with reperfusion status rather than recanalization in patients with ischemic stroke, how to address the no-reflow phenomenon is critical. But effective treatments for restoring cerebral microcirculation have not been well established until now, so there is an urgent need for novel therapeutic perspectives to improve outcomes after recanalization therapies. CONCLUSION: Here, we review the occurrence of the no-reflow phenomenon after ischemic stroke and discuss its impact, detection method, and therapeutic strategies on the course of ischemic stroke, from basic science to clinical findings.

Single-Hole Janus Hollow Sphere.

Cross-linked epoxy resin (EP) single-hole Janus hollow spheres are prepared by cross-linking induced phase separation within an emulsion droplet and selective modification. The droplet is composed of an EP oligomer, toluene, and hexadecane. 2-Ethyl-4-methylimidazole is used as the cross-linker added to the aqueous phase. During the cross-linking, hexadecane forms an eccentric core in the cross-linked EP sphere. A single hole forms across the shell after dissolving the solvents, and a single-hole hollow sphere is achieved. The hole and cavity size are controlled by adjusting the solvent content and cross-linker concentration. Furthermore, frozen wax is used as the core material instead of hexadecane to effectively protect the sphere's interior surface. Selective modification of the exterior and interior surfaces is thus permitted. As an example, a responsive single-hole Janus hollow sphere is prepared by the favorable growth of a silica-polyoxyethylene composite layer onto the exterior surface and a selective grafting of poly(2-diethylaminoethyl methacrylate) (PDEAEMA) by atom-transfer radical polymerization (ATRP) onto the interior. The Janus sphere is water-dispersible and controllably captures and releases oil from the aqueous environment as triggered by the pH value.

Vacancy defect-promoted nanomaterials for efficient phototherapy and phototherapy-based multimodal Synergistic Therapy.

Phototherapy and multimodal synergistic phototherapy (including synergistic photothermal and photodynamic therapy as well as combined phototherapy and other therapies) are promising to achieve accurate diagnosis and efficient treatment for tumor, providing a novel opportunity to overcome cancer. Notably, various nanomaterials have made significant contributions to phototherapy through both improving therapeutic efficiency and reducing side effects. The most key factor affecting the performance of phototherapeutic nanomaterials is their microstructure which in principle determines their physicochemical properties and the resulting phototherapeutic efficiency. Vacancy defects ubiquitously existing in phototherapeutic nanomaterials have a great influence on their microstructure, and constructing and regulating vacancy defect in phototherapeutic nanomaterials is an essential and effective strategy for modulating their microstructure and improving their phototherapeutic efficacy. Thus, this inspires growing research interest in vacancy engineering strategies and vacancy-engineered nanomaterials for phototherapy. In this review, we summarize the understanding, construction, and application of vacancy defects in phototherapeutic nanomaterials. Starting from the perspective of defect chemistry and engineering, we also review the types, structural features, and properties of vacancy defects in phototherapeutic nanomaterials. Finally, we focus on the representative vacancy defective nanomaterials recently developed through vacancy engineering for phototherapy, and discuss the significant influence and role of vacancy defects on phototherapy and multimodal synergistic phototherapy. Therefore, we sincerely hope that this review can provide a profound understanding and inspiration for the design of advanced phototherapeutic nanomaterials, and significantly promote the development of the efficient therapies against tumor.

Janus Nanoparticle Coupled Double-Network Hydrogel.

For double network (DN) hydrogels, their performance can be tuned by adjusting the interaction between their two networks. A novel DN hydrogel toughening approach is proposed by employing Janus nanoparticles (JNs) as crosslinkers to gain a conjoined-network hydrogel. First, a kind of JNs modified by amino groups and quaternary ammonium salt is synthesized, named R3 N+ -JN-NH2 . The DN hydrogel is fabricated based on ionic coordination between calcium chloride (CaCl2 ) and sodium alginate (Alg), as well as covalent (benzoic imine) between glycol chitosan (GC) and benzaldehyde-capped poly(ethylene oxide) (BzCHO-PEO-BzCHO). Based on the same covalent and ionic dynamic crosslinking mechanism, the added R3 N+ -JN-NH2 interacts with two networks to promote crosslinking to form a dually crosslinked structure. The R3 N+ -JN-NH2 effectively provides more energy dissipation, and the hydrogel with conjoined networks shows better compression resistance.

Ultrathin Nanosheet-Supported Ag@Ag2O Core-Shell Nanoparticles with Vastly Enhanced Photothermal Conversion Efficiency for NIR-II-Triggered Photothermal Therapy.

Photothermal therapy (PTT) working in the second near-infrared (NIR-II) region has aroused a huge interest due to its potential application in terms of clinical cancer treatment. However, owing to the lack of photothermal nanoagents with high photothermal conversion efficiency, NIR-II-driven PTT still suffers from poor efficiency and subsequent cancer recurrence. In this work, we show a new and highly efficient preparation approach for NIR-II photothermal nanoagents and tailor ultrathin layered double hydroxide (LDH)-supported Ag@Ag2O core-shell nanoparticles (Ag@Ag2O/LDHs-U), vastly improving NIR-II photothermal performance. A combination study (high-resolution transmission electron microscopy (HRTEM), extended X-ray absorption fine structure spectroscopy (EXAFS), and X-ray photoelectron spectroscopy (XPS)) verifies that ultrafine Ag@Ag2O core-shell nanoparticles (∼3.8 nm) are highly dispersed and firmly immobilized within ultrathin LDH nanosheets, and their Ag2O shell possesses abundant vacancy-type defects. These unique Ag@Ag2O/LDHs-U display an impressive photothermal conversion efficiency as high as 76.9% at 1064 nm. Such an excellent photothermal performance is likely attributed to the enhanced localized surface plasmon resonance (LSPR) coupling effect between Ag and Ag2O and the reduced band gap caused by vacancy-type defects in the Ag2O shell. Meanwhile, Ag@Ag2O/LDHs-U also show prominent photothermal stability, due to the unique supported core-shell nanostructure. Moreover, both in vitro and in vivo studies further confirm that Ag@Ag2O/LDHs-U possess good biocompatible properties and outstanding PTT therapeutic efficacy in the NIR-II region. This research shows a new strategy in the rational design and preparation of an efficient photothermal agent, which is helpful to achieve more accurate and effective cancer theranostics.

Combination of Polyethylene Glycol-Conjugated Urokinase Nanogels and Urokinase for Acute Ischemic Stroke Therapeutic Implications.

Tissue reperfusion is a serious therapeutic strategy of ischemic stroke in addition to recanalization. In this work, we aimed to establish new urokinase-based therapeutics in order to dissolve large vessel thrombus together with microthrombi for stroke implications. Formulations consisted of free urokinase (UK), polyethylene glycol-crosslinked urokinase nanogel (PEG-UK), and a 1:1 mixture of UK and PEG-UK (PEG-UK+UK) were tested both in vitro and in vivo. In vitro experiments confirmed the pH-dependent release of PEG-UK in the PEG-UK+UK formulation. It was activated at pH 6.50, an environmental pH in the infarct brain tissue, owing to the dynamic crosslink property of PEG-UK. In vivo tests on a thromboembolic stroke rat model showed that the formulations containing UK, i.e., free UK and PEG-UK+UK, demonstrated better neurological scores and smaller infarction volumes within the time window, in which the PEG-UK+UK formulation relatively performed better. On the other hand, the formulations containing PEG-UK, i.e., PEG-UK and PEG-UK+UK, gained sufficient thrombolytic efficiency beyond the time window. Further investigation on the mechanism revealed that PEG-UK could reduce microthrombus in distal microcirculation, and its destructive effect was also less than that of free UK. The PEG-UK+UK formulation actually provided a "dual targeting" delivery of UK to both the large vessels and the microcirculation, which was beneficial to the treatment of cerebral ischemic stroke both within and beyond the therapeutic time window.

Highly efficient photothermal heating via distorted edge-defects in boron quantum dots.

Quantum dots (QDs) are increasingly being utilized as near infrared (NIR) active photothermal agents for cancer diagnosis and therapy, with the main emphasis of current research being the enhancement of photothermal conversion efficiencies. Herein, we report the facile synthesis of 2-3 nm boron quantum dots (B QDs), which demonstrated a remarkable photothermal conversion efficiency of 57% under NIR excitation. This outstanding performance can be attributed to the alteration of the electronic structure, which was a result from the distorted edge-effect induced by the unique empty orbit of B atoms in the B QDs. These results can be verified by B K-edge near edge X-ray absorption fine structure (NEXAFS), high-resolution transmission electron microscopy (HR-TEM) and density functional theory (DFT) calculations. The results demonstrate that B QDs represent a promising new and non-toxic agent for both multimodal NIR-driven cancer imaging and photothermal therapy. This work thus identifies B QDs as an exciting new and theranostic agent for cancer therapy. Furthermore, the synthetic strategy used here to synthesize the B QDs was simple and easily scalable.

Biphasic Double-Network Hydrogel With Compartmentalized Loading of Bioactive Glass for Osteochondral Defect Repair.

Periarticular injury usually causes the defects of superficial cartilage and the underlying subchondral bone. Although some efficacious outcomes have been achieved by the existing therapeutic methods both in clinics and research, like symptomatic treatment, microfracture surgery, and tissue engineering technology, they still present specific disadvantages and complications. To improve this situation, we designed a biphasic (bi-) scaffold aiming to repair the structure of cartilage and subchondral bone synchronously. The scaffold consisted of a superior double-network (DN) hydrogel layer and a lower bioactive glass (BG) reinforced hydrogel layer, and the DN hydrogel included glycol chitosan (GC) and dibenzaldhyde functionalized poly(ethylene oxide) network, and sodium alginate (Alg) and calcium chloride (CaCl2) network. To investigate its effectiveness, we applied this biphasic scaffold to repair osteochondral full-thickness defects in rabbit models. We set up six observation groups in total, including Untreated group, Microfracture group, BG only group, DN gel group, bi-DN gel group, and bi-DN/TGF-ß gel group. With a follow-up period of 24 weeks, we evaluated the treatment effects by gross observation, micro-CT scan and histological staining. Besides, we further fulfilled the quantitative analysis of the data from ICRS score, O'Driscoll score and micro-CT parameters. The results revealed that neat GC/Alg DN hydrogel scaffold was only conductive to promoting cartilage regeneration and neat BG scaffold merely showed the excellent ability to reconstruct subchondral bone. While the biphasic scaffold performed better in repairing osteochondral defect synchronously, exhibiting more well-integrated cartilage-like tissue with positive staining of toluidine blue and col II immunohistochemistry, and more dense trabecular bone connecting closely with the surrounding host bone. Therefore, this method possessed the clinical application potential in treating articular injury, osteochondral degeneration, osteochondral necrosis, and sclerosis.

Protein-Carbon Dot Nanohybrid-Based Early Blood-Brain Barrier Damage Theranostics.

For effective treatment of ischemic cerebral thrombosis, it is of great significance to find a facile way in assessing the early damage of blood-brain barrier (BBB) after ischemic stroke during thrombolysis by integrating thrombolytic agents with fluorescent materials. Herein, a novel type of protein-carbon dot  nanohybrids is reported by the incorporation of carbon dots on thrombolytic agents through covalent linkage. Both in vitro and ex vivo fluorescence imaging measurements have demonstrated remarkable imaging effects in the brain of transient middle cerebral artery occlusion mice. Besides, the outstanding thrombolytic capacity of the nanohybrids was determined by in vitro thrombolysis tests. As one of the few reports of the construction of thrombolytic agents and fluorescent nanomaterials, the nanohybrids retain thrombolysis ability and fluorescent traceability simultaneously. It may provide a promising indicator for early BBB damage and thrombolytic agent distribution to estimate the possibility of symptomatic intracranial hemorrhage after thrombolysis and supply tissue window evidence for clinical thrombolytic agent application.

Exploiting Single Atom Iron Centers in a Porphyrin-like MOF for Efficient Cancer Phototherapy.

In recent years, single-atom catalysts (SACs) have attracted enormous attention due their effectiveness in promoting a variety of catalytic reactions. However, the ability of SACs to enhance cancer phototherapies has received little attention to date. Herein, we synthesized a metal organic framework (MOF) rich in porphyrin-like single atom Fe(III) centers (denoted herein as porphyrin-MOF or P-MOF) and then evaluated the performance of the P-MOF for cancer treatment by photodynamic therapy (PDT) and photothermal therapy (PTT) under NIR (808 nm) irradiation, as well as photoacoustic imaging (PAI) of tumors. On acccount of the abundance of single atom Fe(III) centers, the P-MOF material demonstrated excellent performance for modulation of the hypoxic tumor microenvironment of Hela cell tumors in mice, while also demonstrating good properties as a photoacoustic imaging (PAI) agent. Density functional theory (DFT) calculations were used to elucidate the superior performance of P-MOF in these applications relative to Fe2O3 (a Fe(III) reference compound). The calculations revealed that the narrow band gap energy of P-MOF (1.31 eV) enabled strong absorption of NIR photons, thereby inducing nonradiative transitions that converted incident light into heat to promote PTT. Further, a facile change of the spin state of the single atom Fe(III) centers in P-MOF under NIR irradiation transformed coordinated triplet oxygen (3O2) to singlet oxygen (1O2), benefiting PDT. This work demonstrates the great future potential of both SACs and MOFs as multifunctional agents for cancer treatment and tumor imaging.

An Injectable Strong Hydrogel for Bone Reconstruction.

For treating bone defects in periarticular fractures, there is a lack of biomaterial with injectable characteristics, tough structure, and osteogenic capacity for providing a whole-structure support and osteogenesis in the defect area. An injectable hydrogel is an ideal implant, however is weak as load-bearing scaffolds. Herein, a new strategy, i.e., an in situ formation of "active" composite double network (DN), is raised for the preparation of an injectable strong hydrogel particularly against compression. As a demonstration, 4-carboxyphenylboronic acid grafted poly(vinyl alcohol) (PVA) is crosslinked using calcium ions to provide a tough frame while bioactive glass (BG) microspheres are associated by poly(ethylene glycol) to obtain an interpenetrated inorganic network for reinforcement. The injected PVA/BG DN hydrogel gains compressive strength, modulus, and fracture energy of 34 MPa, 0.8 MPa, and 40 kJ m-2 , respectively. Then, the properties can be "autostrengthened" to 57 MPa, 2 MPa, and 65 kJ m-2 by mineralization in 14 days. In vivo experiments prove that the injected DN hydrogel is more efficient to treat femoral supracondylar bone defects than the implanted bulk DN gel. The work suggests a facile way to obtain a strong hydrogel with injectability, cytocompatibility, and tailorable functionality.

Vacancy-enhanced generation of singlet oxygen for photodynamic therapy.

Oxygen vacancy (OV) engineering in semiconductors can greatly enhance the separation of photo-induced electron-hole pairs, thereby enhancing the photocatalytic activity. Taking inspiration from this, we prepared a novel BiOBr-H/Rub2d composite by functionalizing OV-rich BiOBr (named BiOBr-H) with a carboxyl functionalized ruthenium photosensitizer (Ru(bpy)2C-pyCl2, abbreviated as Rub2d), which was then successfully applied for photodynamic therapy (PDT). Density functional theory (DFT) calculations confirmed efficient electron transfer from the Rub2d complex to the intermediate energy level of BiOBr-H under visible light irradiation. In vitro and in vivo studies demonstrated that BiOBr-H/Rub2d was a superior agent for photodynamic therapy compared with the free ruthenium complex. The theoretical and experimental data presented thus reveal for the first time that abundant OVs in BiOBr-H can significantly improve the photocatalytic activity of a photosensitizer, resulting in the generation of more reactive oxygen species to enhance PDT. The findings of this study thus offer a new strategy for the development of highly efficient cancer therapies.

Injectable Adhesive Hydrogel through a Microcapsule Cross-Link for Periodontitis Treatment.

In this work, chitosan (CS) decorated metronidazole (MTZ) microcapsules (CS@MTZ) were synthesized and used as a cross-linker for the preparation of a poly(vinyl alcohol) (PVA) injectable hydrogel by dynamic covalent bonding and ionic interaction through a 4-carboxyphenylboronic acid bridge. The use of MTZ microcapsules efficiently slowed down the release rate of the hydrophilic antibiotic from the hydrogel matrix. Besides, the hydrophobicity of the microcapsules endows the PVA@CS@MTZ hydrogel to be sticky to a substrate in wet conditions, under a suggested mechanism of evicting the water boundary layer on the substrate. The sustained release behavior endowed a prolonged bacteriostasis ability of the hydrogel formulation for up to 14 days in vitro, and the bioadhesive property as well as the injectability of the hydrogel benefited the topical delivery of MTZ in periodontal pockets and exhibited desirable antibacterial capacity in 1 week on the rat periodontitis model.