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Locoregional injectable tumoral theranostic nanocomposite hydrogels have shown great potential for clinical transformation, owing to their integration of the advantageous features of both systems, whilst simultaneously minimizing their drawbacks. However, how the nanomedicines efficiently escape from hydrogel and circumvent the intrinsically conflicting attributes between tumor penetration and accumulation directly determines the theranostic efficiency. Herein, a cluster missile‐inspired dynamic nanocomposite hydrogel synthesized via Schiff base reaction between crosslinked synergistic size‐changeable nano‐prodrugs (NPs) and glutaraldehyde (GA) is successfully developed. The hydrogel, analogous to a cluster missile, can efficiently release NPs with an initial size of 25.3 nm for deep tumor distribution and cellular internalization by responding to the tumoral extracellular pH, while precisely directing their exceptionally high cellular accumulation and highly selective drug release in response to the tumoral intracellular pH/glutathione (GSH), thereby achieving robust locoregional chemotherapy. Furthermore, platinum heavy metals within NPs confer upon the hydrogel an ability to spatiotemporally monitor dynamic changes in both itself and tumor tissues without necessitating additional conventional imaging agents. Thus, such a cluster missile‐inspired dynamic nanocomposite hydrogel paves the way toward clinical use for precise locoregional tumor theranostics. [ABSTRACT FROM AUTHOR]

Endometriosis is a prevalent gynecological condition characterized by chronic pelvic pain, dysmenorrhea, and infertility, affecting ≈176 million women of reproductive age worldwide. Current treatments, including pharmacological and surgical interventions, are often associated with significant side effects and high recurrence rates. Consequently, there is an urgent need for innovative and safer therapeutic approaches. In this study, an injectable magnetic hydrogel nanosystem is developed designed for the dual‐purpose magnetothermal and anti‐inflammatory treatment of endometriosis. This hydrogel incorporates Fe3O4 nanoparticles alongside an anti‐inflammatory peptide. Upon magnetic activation, the Fe3O4 nanoparticles induce a localized hyperthermic response, raising the temperature of endometriotic lesions to 63.3 °C, effectively destroying endometriotic cells. Concurrently, the thermally responsive hydrogel facilitates the controlled release of the anti‐inflammatory peptide, thus modulating the inflammatory milieu. The biocompatibility and complete in vivo degradability of the hydrogel further enhance its therapeutic potential. The in vivo studies demonstrated that this injectable magnetic hydrogel system achieved a 90% reduction in the volume of endometriotic lesions and significantly decreased inflammatory markers, offering a promising non‐invasive treatment modality for endometriosis. By integrating precise lesion ablation with the modulation of the inflammatory microenvironment, this system represents a novel approach to the clinical management of endometriosis. [ABSTRACT FROM AUTHOR]

Background: Oral and maxillofacial tissue defects resulting from factors such as trauma or infection, can significantly impact both facial function and aesthetics. Additionally, the complex anatomical structure of the face often increases the difficulty of treatment. With the advantages of controlled release, targeted delivery, and enhanced mechanical properties, injectable hydrogels have been investigated for the treatment of oral and maxillofacial diseases. In the field of regeneration, injectable hydrogels have a structure similar to the extracellular matrix (ECM) and are biocompatible, which can be used as scaffolds for tissue regeneration. Objective: This review aims to summarize the literature on the current status and limitations of injectable hydrogels in the field of oral tissue regeneration. Methods: We searched Pubmed and Web of Science databases to find and summarize the articles on the application of injectable hydrogels in tissue regeneration. Conclusions: This review focuses on the current status and limitations of injectable hydrogels in the field of tissue regeneration (periodontal tissue, dentin‐pulp complex, bone and cartilage, salivary gland regeneration, and mucosal repair). Although fully studied in animal models, there are still challenges in clinical transformation of injectable hydrogels in promoting tissue regeneration. [ABSTRACT FROM AUTHOR]

Injectable hydrogels for cancer immunotherapy are effective for both active and passive approaches. Tumor‐infiltrating lymphocyte (TIL) immunoshaping can change the tumor microenvironment to favor tumor cell elimination. The primary objective of immunoshaping is to reduce regulatory T‐cells (Tregs), which can enhance the effectiveness of ex vivo immune cell therapy in solid tumors. A shear‐thinning injectable hydrogel that consists of gelatin and Laponite (Gel‐Lap) is used in this study. By optimizing the formulation, their immunotherapeutic and anti‐tumor properties are examined. Gemcitabine (GEM), an anti‐metabolite cancer chemotherapy agent, is loaded into a Gel‐Lap hydrogel (immunogel). The study compares the effects of immunogel on 4T1 inoculated breast cancer animal models. Results show that immunogel increases survival rates and significantly inhibits metastasis. The Treg cell population reduction is observed up to 70% in TILs and splenocyte population in line with CD8+ T‐cells population increment in inguinal lymph nodes near the tumor region; the CD8+ T‐cells function may be mediated through overexpression of eomesodermin (EOMES) as cytotoxic T lymphocyte (CTL) activation transcription factor. The human 3D cell culture model confirmed results in animal data demonstrating T‐cell migration through the hydrogel and anticancer efficacy. Local delivery of GEM using our silicate‐based hydrogel holds promise for editing tumor microenvironment in favor of systemic immune responses. [ABSTRACT FROM AUTHOR]

In order to overcome the harmful effects of radiation exposure on lung tissue in radiation therapy, a complete comparative analysis was performed between the injectable pure hydrogel and a novel composite hydrogel, taking into account the addition of cellulose nanoparticles in varying ratios. Initially, both chitosan and tragacanth hydrogels were chemically were modified, and then characterized by FTIR spectroscopy and rheology measurement. For in vivo studies, 42 rats were divided into seven groups. Rats in group 1, were not exposed to radiation, and no injection was done. Rats in group 2 were exposed to a radiation dose of 15 Gy without any injection. Rats in groups 3, 4, and 5 got injectable chitosan/ tragacanth hydrogel containing nanocellulose 25, 50, and 75 mg/kg BW, respectively, along with a radiation dose of 15 Gy. Rats in group 6 got a radiation dose of 15 Gy and an IP injection optimal dose of cellulose nanoparticle and PBS. Rat in group 7 got a radiation dose of 15 Gy and an IP injection of hydrogel containing only chitosan–tragacanth. The pathological results demonstrated that the 25 mg/kg BW dose of nanocellulose‐contained hydrogel possessed less inflammation, mucus secretion, bleeding in lung tissue, and air sac wall thickening than other groups. In addition, a biochemistry assessment was conducted by examining the activity of three enzymes of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxide (GPx), which findings confirmed the hydrogel incorporated with 25 mg/kg BW dose of nanocellulose decreased cell death in a lung tissue damaged by radiation which was 52 IU/mL, 37 IU/mL, and 10 μM in comparison with 63 IU/mL, 40 IU/mL, and 1 μM for the control sample. [ABSTRACT FROM AUTHOR]

Injectable, tissue mimetic, bioactive, and biodegradable hydrogels offer less invasive regeneration and repair of tissues. The monitoring swelling and in vitro degradation capacities of hydrogels are highly important for drug delivery and tissue regeneration processes. Bioactivity of bone tissue engineered constructs in terms of mineralized apatite formation capacity is also pivotal. We have previously reported in situ forming chitosan‐based injectable hydrogels integrated with hydroxyapatite and heparin for bone regeneration, promoting angiogenesis. These hydrogels were functionalized by glycerol and pH to improve their mechano‐structural properties. In the present study, functionalized hybrid hydrogels were investigated for their swelling, in vitro degradation, and bioactivity performances. Hydrogels have degraded gradually in phosphate‐buffered saline (PBS) with and without lysozyme enzyme. The percentage weight loss of hydrogels and their morphological and chemical properties, and pH of media were analyzed. The swelling ratio of hydrogels (55%–68%(wt), 6 h of equilibrium) indicated a high degree of cross‐linking, can be suitable for controlled drug release. Hydrogels have gradually degraded reaching to 60%–70% (wt%) in 42 days in the presence and absence of lysozyme, respectively. Simulated body fluid (SBF)‐treated hydrogels containing hydroxyapatite‐induced needle‐like carbonated‐apatite mineralization was further enhanced by heparin content significantly. [ABSTRACT FROM AUTHOR]

Surgical resection remains the mainstream treatment for malignant melanoma. However, challenges in wound healing and residual tumor metastasis pose significant hurdles, resulting in high recurrence rates in patients. Herein, a bioactive injectable hydrogel (BG‐Mngel) formed by crosslinking sodium alginate (SA) with manganese‐doped bioactive glass (BG‐Mn) is developed as a versatile platform for anti‐tumor immunotherapy and postoperative wound healing for melanoma. The incorporation of Mn2+ within bioactive glass (BG) can activate the cGAS‐STING immune pathway to elicit robust immune response for cancer immunotherapy. Furthermore, doping Mn2+ in BG endows system with excellent photothermal properties, hence facilitating STING activation and reversing the tumor immune‐suppressive microenvironment. BG exhibits favorable angiogenic capacity and tissue regenerative potential, and Mn2+ promotes cell migration in vitro. When combining BG‐Mngel with anti‐PD‐1 antibody (α‐PD‐1) for the treatment of malignant melanoma, it shows enhanced anti‐tumor immune response and long‐term immune memory response. Remarkably, BG‐Mngel can upregulate the expression of genes related to blood vessel formation and promote skin tissue regeneration when treating full‐thickness wounds. Overall, BG‐MnGel serves as an effective adjuvant therapy to regulate tumor metastasis and wound healing for malignant melanoma. [ABSTRACT FROM AUTHOR]

The microvascular network plays an important role in providing nutrients to the injured tissue and exchanging various metabolites. However, how to achieve efficient penetration of the injured tissue is an important bottleneck restricting the reconstruction of microvascular network. Herein, the hydrogel precursor solution can efficiently penetrate the damaged tissue area, and ultrasound triggers the release of thrombin from liposomes in the solution to hydrolyze fibrinogen, forming a fibrin solid hydrogel network in situ with calcium ions and transglutaminase as catalysts, effectively solving the penetration impedance bottleneck of damaged tissues and ultimately significantly promoting the formation of microvascular networks within tissues. First, the fibrinogen complex solution is effectively permeated into the injured tissue. Second, ultrasound triggered the release of calcium ions and thrombin, activates transglutaminase, and hydrolyzes fibrinogen. Third, fibrin monomers are catalyzed to form fibrin hydrogels in situ in the damaged tissue area. In vitro studies have shown that the fibrinogen complex solution effectively penetrated the artificial bone tissue within 15 s after ultrasonic triggering, and formed a hydrogel after continuous triggering for 30 s. Overall, this innovative strategy effectively solved the problem of penetration resistance of ultrasound‐triggered hydrogels in the injured tissues, and finally activates in situ microvascular networks regeneration. [ABSTRACT FROM AUTHOR]

The primary request nowadays is for innovative and superior scaffold designs that mimic the characteristics of native tissue in cartilage tissue engineering. GelMA/Alginate (G/A) interpenetrating polymer network (IPN) has become a popular hydrogel material for tissue engineering because of its superior mechanical and biological properties. Here, to balance the properties, a hydrogel composed of G/A and covalent organic frameworks (COF) nanoparticles is specially designed. In this study, a hydrogel of GelMA/Alginate/COF (G/A/C) with improved properties such as pore size, swelling, mechanical strength, shear‐thinning behavior, and biocompatibility is produced. Furthermore, the G/A/C hydrogel facilitate the printing of complex three dimensional (3D) scaffolds. The test result demonstrates that the addition of COF up to 1% (w/w) enhances the porosity and decreases pore size (0.2 times), improves the compression strength (six times), and decreases the degradation ratio (0.05 times) and the swelling (0.3 times) compared to the G/A hydrogel sample. Besides, the cell viability test confirms the cell growth during the incubation and great biological behavior (more than 98%). The suitable performance of the G/A hydrogel containing 1% COF and its shape fidelity during the injection by 3D printer is confirmed. Nanocomposite IPN hydrogel based on G/A/C could be useful in tissue engineering applications. [ABSTRACT FROM AUTHOR]

Collagen nanofibers can be employed in hydrogels to create injectable nanocomposite hydrogels, mimicking the fibrous architecture of the natural extracellular matrix (ECM). As long continuous electrospun collagen nanofibers are not applicable, fragmentation is inevitable to obtain injectable hydrogels with a fine viscosity. Here, four methods: hand grinding (HG), homogenizer (HM), mixer milling (MM), and ultrasonication (UH) are used to disintegrate and shorten collagen nanofiber mats before incorporation into an injectable hyaluronic acid hydrogel as a matrix. The Length‐to‐diameter (L/d) ratio and morphology of fragmented collagen are compared by SEM. The injection force, mechanical properties, and cell viability of the selected collagen‐incorporated hydrogels are also evaluated. UH emerges as the most effective method, yielding the highest L/d ratio of 46 and a notable compressive modulus of 8.7 ± 0.92 kPa. Assessment of the in vitro cell viability of the encapsulated chondrocytes in the collagen‐incorporated hydrogels demonstrates good biocompatibility, and hydrogels containing UH short nanofiber, in particular, show an increase in cell proliferation. This work indicates how collagen mats can be effectively broken down and combined with injectable hydrogels to enhance both their mechanical behavior and biocompatibility. [ABSTRACT FROM AUTHOR]

For various chronic wounds, bacterial infection is one of the important reasons that hinder their healing. Ion‐crosslinked antibacterial hydrogel dressings based on Ag+, Cu2+ and Zn2+, have made progress in clinical application. However, the toxicity of released metal ions cannot be ignored. Therefore, how to ensure the antibacterial performance of hydrogel dressing while reducing the amount of metal ions is a major challenge for the fabrication of metal ion based antibacterial hydrogel. In this study, a general method is proposed to design cationic ion‐crosslinked hydrogel based on thiourea groups. Taking the hydrogel formed by mixing thiourea modified hyaluronic acid (H‐ANCSN) with Ag+ (HA‐NCSN/Ag+ hydrogel) as an example, the characteristics and application potential of this kind of hydrogel are thoroughly explored. Due to the strong cationic chelation characteristics of thiourea groups, HA‐NCSN/Ag+ hydrogel can gel at low Ag+ concentration and achieve long‐term slow release of Ag+ at stable concentration to balance the antibacterial and biocompatible properties. Moreover, this dynamic thiourea‐Ag+ crosslinking also endowed the hydrogel with the property of "gelation and encapsulation first, injection to cover wound when necessary". Then, the mangiferin self‐assembled nanoparticles are loaded into HA‐NCSN/Ag+ hydrogel as the radical oxygen species scavenger. [ABSTRACT FROM AUTHOR]

Injectable hyaluronic acid (HA) hydrogel plays an important role in dermal filling. However, conventional HA dermal fillers mostly lack bio‐functional diversity and frequently cause adverse reactions because of the chemical stiffness of highly modified degree and crosslinker residues. In this study, polylactic acid (PLA) was embedded into HA hydrogel as a bioactive substance and 1,4‐butanediol diglycidyl ether was used as a crosslinker to prepare the HA/PLA composite hydrogel with enhanced biocompatibility and biological performance. We aimed to investigate the properties of HA/PLA composite hydrogels as dermal fillers by assessing the rheological properties, surface microstructure, enzymolysis stability, swelling ratio, degradation rate, cytotoxicity, and anti‐wrinkle effect on photo‐aged skin. The results showed that the stability and stiffness of the composite hydrogel decreased with an increasing amount of PLA, while the in vivo safety of the HA/PLA hydrogel was enhanced, showing no adverse reactions such as edema, redness, or swelling. Moreover, the composite hydrogel with 2 wt% PLA exhibited excellent anti‐wrinkle effects, showing the highest collagen production. Thus, the PLA‐embedded HA composite hydrogel showed potential as a dermal filler with high safety, easy injectability, and excellent anti‐wrinkle effects. [ABSTRACT FROM AUTHOR]

An ideal hydrogel for stem cell therapy would be injectable and efficiently promote stem cell proliferation and differentiation in body. Herein, an injectable, single‐component hydrogel with hyaluronic acid (HA) modified with phenylboronic acid (PBA) and spermidine (SM) is introduced. The resulting HAps (HA‐PBA‐SM) hydrogel is based on the reversible crosslinking between the diol and the ionized PBA, which is stabilized by the SM. It has a shear‐thinning property, enabling its injection through a syringe to form a stable hydrogel inside the body. In addition, HAps hydrogel undergoes a post‐injection "self‐curing," which stiffens the hydrogel over time. This property allows the HAps hydrogel to meet the physical requirements for stem cell therapy in rigid tissues, such as bone, while maintaining injectability. The hydrogel enabled favorable proliferation of human mesenchymal stem cells (hMSCs) and promoted their differentiation and mineralization. After the injection of hMSCs‐containing HAps into a rat femoral defect model, efficient osteogenic differentiation of hMSCs and bone regeneration is observed. The study demonstrates that simple cationic modification of PBA‐based hydrogel enabled efficient gelation with shear‐thinning and self‐curing properties, and it would be highly useful for stem cell therapy and in vivo bone regeneration. [ABSTRACT FROM AUTHOR]

Chronic periodontitis poses long-term challenges in dentistry, requiring the development of innovative dental composites with biocompatibility, bone regeneration, and antibacterial properties. This study focuses on synthesis of novel injectable thermoresponsive hydrogels composed of chitosan, sodium bicarbonate, bioactive glass (20 and 40% w/w), and acetanilide drug (0.3 and 0.6% w/w). These hydrogels exhibit a sol-gel transition at 37°C, addressing periodontal challenges with reduced gelation time. The smooth flow characteristic was evaluated through 17-22 gauge syringe needles at low temperature. Rheological studies demonstrated pseudoplastic behavior, with viscosity decreasing as shear rate increases. Fourier transform infrared and x-ray diffraction analysis confirmed the bioactivity of hydrogels, forming a bone-like apatite layer in simulated body fluid. The drug-loaded hydrogels demonstrated promising in vitro antibacterial properties against dental pathogens, specifically Staphylococcus aureus and Pseudomonas aeruginosa. Drug dissolution analysis revealed relatively high release rate at 37°C, highlighting its role in rapidly eliminating bacterial colonies at the target site, while the subsequent sustained release contributes to the prevention of infection recurrence. Finally, biocompatibility was assessed with fibroblast, where the cells were observed anchoring into the polymeric chains of hydrogel through extended filopodia. [ABSTRACT FROM AUTHOR]

The combination of the first‐line standard chemotherapeutic drug doxorubicin hydrochloride (DOX) and the molecular‐targeted drug Herceptin (HCT) has emerged as a promising strategy for human epidermal growth receptor 2 (HER‐2) overexpressing breast cancer treatment. However, insufficient drug accumulation and severe cardiotoxicity are two major challenges that limit its clinical application. Herein, an in situ forming gold nanorods (AuNRs)‐sodium alginate (ALG) hybrid hydrogel encapsulating DOX and HCT was engineered for tumor synergistic therapy involving injectable, dual‐stimuli‐responsive drug release, photothermal ablation, and drug‐antibody synergistic therapy. The photothermal agent AuNRs, anticancer drug DOX, and anticancer antibody HCT were mixed in ALG solution, and after injection, the soluble ALG was quickly transformed into a hydrogel in the presence of Ca2+ in the body. Significantly, the hybrid hydrogel exhibits an extremely high photothermal conversion efficiency of 70% under 808 nm laser irradiation. The thermal effect can also provide photothermal stimulation to trigger the drug release from the gel matrix. In addition, the drug release rate and the releasing degree are also sensitive to the pH. In vitro studies demonstrated that the PEI‐AuNR/DOX/HCT/ALG hydrogel has facilitated the therapeutic efficiency of each payload and demonstrated a strong synergistic killing effect on SK‐BR‐3 cells. In vivo imaging results showed that the local drug delivery system can effectively reduce the nonspecific distribution in normal tissues and increase drug concentration at tumor sites. The proposed hydrogel system shows significant clinical implications by easily introducing a sustainable photothermal therapy and a potential universal carrier for the local delivery of multiple drugs to overcome the challenges faced in HER‐2 overexpressing cancer therapy. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) have been recognized as prevalent contributors to the development of inner retinal injuries including optic neuropathies such as glaucoma, non‐arteritic anterior ischemic optic neuropathy, traumatic optic neuropathy, and Leber hereditary optic neuropathy, among others. This underscores the pivotal significance of oxidative stress in the damage inflicted upon retinal tissue. To combat ROS‐related challenges, this study focuses on creating an injectable and tissue‐adhesive hydrogel with tailored antioxidant properties for retinal applications. GelCA, a gelatin‐modified hydrogel with photo‐crosslinkable and injectable properties, is developed. To enhance its antioxidant capabilities, curcumin‐loaded polydopamine nanoparticles (Cur@PDA NPs) are incorporated into the GelCA matrix, resulting in a multifunctional nanocomposite hydrogel referred to as Cur@PDA@GelCA. This hydrogel exhibits excellent biocompatibility in both in vitro and in vivo assessments, along with enhanced tissue adhesion facilitated by NPs in an in vivo model. Importantly, Cur@PDA@GelCA demonstrates the potential to mitigate oxidative stress when administered via intravitreal injection in retinal injury models such as the optic nerve crush model. These findings underscore its promise in advancing retinal tissue engineering and providing an innovative strategy for acute neuroprotection in the context of inner retinal injuries. [ABSTRACT FROM AUTHOR]

The injectable hydrogels can deliver the loads directly to the predetermined sites and form reservoirs to increase the enrichment and retention of the loads in the target areas. The preparation and injection of injectable hydrogels involve the sol–gel transformation of hydrogels, which is affected by factors such as temperature, ions, enzymes, light, mechanics (self‐healing property), and pH. However, tracing the injection, degradation, and drug release from hydrogels based on different ways of gelation is a major concern. To solve this problem, contrast agents are introduced into injectable hydrogels, enabling the hydrogels to be imaged under techniques such as fluorescence imaging, photoacoustic imaging, magnetic resonance imaging, and radionuclide imaging. This review details methods for causing the gelation of imageable hydrogels; discusses the application of injectable hydrogels containing contrast agents in various imaging techniques, and finally explores the potential and challenges of imageable hydrogels based on different modes of gelation. [ABSTRACT FROM AUTHOR]

This study focuses on synthesizing an injectable hydrogel (IH) using Moringa oleifera gum (MOG) with multi‐aldehyde groups (MOG‐CHO) and carboxymethyl chitosan (CMCh) through a Schiff base reaction at 37 °C. The study includes the optimal concentration of the oxidizing agent to achieve the best content of aldehydes in Moringa oleifera gum. Furthermore, the best oxidized Moringa oleifera gum decides the least gelation time. The physical properties of the optimized IH (IH‐3‐7) are assessed, including color, gel content, porosity, load‐bearing capacity, syringeability, and self‐healing capability. Structural characterization is performed using Fourier transform Infrared spectroscopy (FT‐IR) and nuclear magnetic spectroscopy (1H NMR), while scanning electron microscope (SEM) and rheometer are used to analyze surface morphology and rheological properties. IH‐3‐7 exhibits a porous structure with 35 % porosity and interconnected holes of 1.45 to 4 μm diameter. Higher swelling at pH 5.5 is shown by swelling ratio test conducted in phosphate buffer saline (PBS) at pH 7.4 and pH 5.5. Ciprofloxacin HCl (Cipro) is loaded into IH for release assays, revealing pH‐dependent drug release. In vitro, cytotoxicity assessments on L‐929 fibroblast cell lines show IH′s biocompatibility. Hydrolytic degradation of IH in PBS at pH 7.4 is also evaluated. [ABSTRACT FROM AUTHOR]

Treating the most widespread complication of diabetes: diabetic wounds poses a significant clinical obstacle due to the intricate nature of wound healing in individuals with diabetes. Here a novel approach is proposed using easily applicable injectable gelatin/metal/tea polyphenol double nanonetworks, which effectively remodel the wound microenvironment and accelerates the healing process. The gelatin(Gel) crosslink with metal ions (Zr4+) through the amino acids, imparting advantageous mechanical properties like self‐healing, injectability, and adhesion. The nanonetwork's biological functions are further enhanced by incorporating the tea polyphenol metal nanonetwork through in situ doping of the epigallocatechin gallate (EGCG) with great antibacterial, self‐healing, antioxidant, and anticancer capabilities. The in vitro and in vivo tests show that this double nanonetworks hydrogel exhibits faster cell migration and favorable anti‐inflammatory and antioxidant properties and can greatly reshape the microenvironment of diabetic wounds and accelerate the wound healing rate. In addition, this hydrogel is completely degraded after subcutaneous injection for 7 days, with nondetectable cytotoxicity in H&E staining of major mice organs and the serum level of liver function indicators. Considering the above‐mentioned merits of this hydrogel, it is believed that the injectable gelatin/metal/tea polyphenol double nanonetworks have broad biomedical potential, especially in diabetic wound repair and tissue engineering. [ABSTRACT FROM AUTHOR]

A review of recent literature reveals a spurt in the publications using alginate dialdehyde (ADA)‐based hydrogels. This study evaluates the stability and characteristics of ADA solutions stored at different temperatures (4 & −20 °C; designated as ADA4°C & ADA−20°C) and durations (1, 3, and 6 months), and gives valuable insights into the shelf life, a parameter important in a clinical setting. ADA solutions were characterized for their viscosity, aldehyde content, molecular weight, and chemical structure before and after storage. The solution viscosities of ADA4°C showed a decreasing trend over 6 months while that of ADA‐20°C showed an increase. Compared to freshly prepared ADA, a significant reduction in aldehyde content, from 40.1±1.4 % to 37.1±1.01 %, was observed for ADA4°C stored for 6 months, but the aldehyde content was stable for ADA−20°C stored for the same period. Molecular weight remained stable (~6800 g/mol) irrespective of the storage temperatures. Injectable hydrogels were prepared by reacting the stored ADA solutions with 20 % aqueous solutions of gelatin. Hydrogels prepared with ADA stored at 4 °C for 6 months showed a significant increase in gelation time from 4.3±1.5 to 8.79±0.1 min and a decrease in degree of crosslinking from 54.3±1.4 % to 29.2±2.3 %. A decreasing trend was observed for properties such as water uptake (from 470 to 961 %) and tensile strength (from 348 to 282 kPa). Hydrogels made with ADA−20°C demonstrated better retention of physicochemical properties over time. In vitro studies revealed that the hydrogels showed a non‐cytotoxic response towards L929 cells irrespective of the storage conditions. LIVE/DEAD assay and F‐Actin staining revealed good cell proliferation on the hydrogels. In conclusion, retention of the properties of ADA in its aqueous solution requires careful control of storage temperatures. [ABSTRACT FROM AUTHOR]

Modulating the inflammatory microenvironment can inhibit the process of inflammatory diseases (IDs). A tri‐cross‐linked inflammatory microenvironment‐responsive hydrogel with ideal mechanical properties achieves triggerable and sustained drug delivery and regulates the inflammatory microenvironment. Here, this study develops an inflammatory microenvironment‐responsive hydrogel (OD‐PP@SeNPs) composed of phenylboronic acid grafted polylysine (PP), oxidized dextran (OD), and selenium nanoparticles (SeNPs). The introduction of SeNPs as initiators and nano‐fillers into the hydrogel results in extra cross‐linking of the polymer network through hydrogen bonding. Based on Schiff base bonds, Phenylboronate ester bonds, and hydrogen bonds, a reactive oxygen species (ROS)/pH dual responsive hydrogel with a triple‐network is achieved. The hydrogel has injectable, self‐healing, adhesion, outstanding flexibility, suitable swelling capacity, optimal biodegradability, excellent stimuli‐responsive active substance release performance, and prominent biocompatibility. Most importantly, the hydrogel with ROS scavenging and pH‐regulating ability protects cells from oxidative stress and induces macrophages into M2 polarization to reduce inflammatory cytokines through PI3K/AKT/NF‐κB and MAPK pathways, exerting anti‐inflammatory effects and reshaping the inflammatory microenvironment, thereby effectively treating typical IDs, including S. aureus infected wound and rheumatoid arthritis in rats. In conclusion, this dynamically responsive injectable hydrogel with a triple‐network structure provides an effective strategy to treat IDs, holding great promise in clinical application. [ABSTRACT FROM AUTHOR]

Hydrogels based on dynamic covalent bonds have unique properties and are competent in many biomedical fields. However, critical issues such as biocompatibility, mechanical properties, and stimulus responsiveness are required to be solved. It is also expected to develop a simple preparation method with mild conditions. Based on these objectives, chitosan (CS), sodium alginate (SA) and 2‐formylphenylboronic acid (2‐FPBA) are used to prepare the dynamic covalent bond hydrogels within minutes neither chemical medications nor severe conditions. Benefiting from the imine borate and boronic ester bonds both formed in the hydrogels, the hydrogels are stable, injectable, and of efficient self‐healing properties. The damage‐recovery process can be repeated for more than 6 cycles. The microstructure of the hydrogels recoded by atomic force microscopy (AFM) is consistent with the mechanical properties and both of them could be affected by the concentrations of SA and 2‐FPBA. Moreover, the dynamic hydrogels are responsive to pH values and oxidative environment. When the model drug 5‐fluorouracil (5‐FU) is loaded in the dynamic hydrogels, the release profiles are sustainable and present significant differences with various stimuli. These dynamic covalent bond hydrogels have a promising prospect in tissue engineering and drug delivery. [ABSTRACT FROM AUTHOR]

Bone defect is still a challenging problem in orthopedic practice. Injectable bone substitutes that can fill different geometry of bone defect and improve biological environment for bone regeneration are attracting attention. Herein, silk fibroin (SF) is noticeable polymer regarding its biocompatible and biodegradable properties. Thus, the calcium phosphate particles incorporated in silk fibroin/methylcellulose (CAPs‐SF/MC) and only methylcellulose (CAPs‐MC) hydrogels are developed and compared their physicochemical properties. Both CAPs‐hydrogels solutions can be administered with a low injectability force of ~6 N, and they require ~40‐min to change to hydrogel at physiological temperature (37°C). The CAPs are evenly distributed throughout the hydrogel matrix and are capable transformed to bioactive hydroxyapatite at pH 7.4. The CAPs in CAPs‐SF/MC have a smaller size than those in CAPs‐MC. Moreover, CAPs‐SF/MC exhibit gradual degradation, as prediction of the degradation mechanism by the Peppas‐Sahlin model and show a greater ability to sustain CAPs release. CAPs‐SF/MC has good biocompatibility with less cytotoxicity in a dose‐dependent manner on mouse preosteoblast cell line (MC3T3‐E1) when compared to CAPs‐MC. CAPs‐SF/MC hydrogels also have better possibility for promoting cell proliferation and differentiation. In conclusion SF incorporated into composite injectable hydrogel potentially improve biological characteristics and may provide clinical advantages. [ABSTRACT FROM AUTHOR]

Aim: The study aimed to develop a bicomponent bioactive hydrogel formed in situ and enriched with an extract of platelet‐rich fibrin (PRFe) and to assess its potential for use in pulp‐dentine complex tissue engineering via cell homing. Methodology: A bicomponent hydrogel based on photo‐activated naturally derived polymers, methacrylated chitosan (ChitMA) and methacrylated collagen (ColMA), plus PRFe was fabricated. The optimized formulation of PRFe‐loaded bicomponent hydrogel was determined by analysing the mechanical strength, swelling ratio and cell viability simultaneously. The physical, mechanical, rheological and morphological properties of the optimal hydrogel with and without PRFe were determined. Additionally, MTT, phalloidin/DAPI and live/dead assays were carried out to compare the viability, cytoskeletal morphology and migration ability of stem cells from the apical papilla (SCAP) within the developed hydrogels with and without PRFe, respectively. To further investigate the effect of PRFe on the differentiation of encapsulated SCAP, alizarin red S staining, RT‐PCR analysis and immunohistochemical detection were performed. Statistical significance was established at p <.05. Results: The optimized formulation of PRFe‐loaded bicomponent hydrogel can be rapidly photocrosslinked using available dental light curing units. Compared to bicomponent hydrogels without PRFe, the PRFe‐loaded hydrogel exhibited greater viscoelasticity and higher cytocompatibility to SCAP. Moreover, it promoted cell proliferation and migration in vitro. It also supported the odontogenic differentiation of SCAP as evidenced by its promotion of biomineralization and upregulating the gene expression for ALP, COL I, DSPP and DMP1 as well as facilitated angiogenesis by enhancing VEGFA gene expression. Conclusions: The new PRFe‐loaded ChitMA/ColMA hydrogel developed within this study fulfils the criteria of injectability, cytocompatibility, chemoattractivity and bioactivity to promote odontogenic differentiation, which are fundamental requirements for scaffolds used in pulp‐dentine complex regeneration via cell‐homing approaches. [ABSTRACT FROM AUTHOR]

A series of injectable polysaccharide hydrogels are prepared with oxidized dextran and diethylenetriamine‐modified carboxymethylcellulose (CMC) or hyaluronic acid (HA). Rheological evaluation reveals that CMC‐based hydrogels achieve storage moduli >1 kPa when prepared from 5 wt% solutions, while storage moduli >100 Pa are achievable from solutions with concentrations as low as 2 wt%. HA‐based hydrogels demonstrate smaller storage moduli but have swelling ratios more than four‐fold that of CMC systems at equal concentrations. The incorporation of N‐diazeniumdiolate nitric oxide (NO) donors into the hydrogels results in reduced hydrogel storage moduli as a function of NO donor concentration. The impact of the hydrogel architecture on NO‐release kinetics proves dependent on the identity of the NO donor. Hydrogel degradation over 14 d indicates that HA‐based hydrogels degrade more rapidly than CMC hydrogels and that the addition of NO to the hydrogels increases the rate at which they degrade. In vitro cytotoxicity of hydrogel extracts is minimal, with toxicity observed only at high NO‐donor concentrations for select cell lines. The diverse properties, versatility, and nontoxic characteristics of these injectable hydrogels should facilitate local delivery of nitric oxide for a range of biomedical applications. [ABSTRACT FROM AUTHOR]

Injectable self‐healing hydrogels have found broad applications in drug delivery, tissue engineering and controlled 3D cell culture. In this article, the coordination interaction between polymer‐bearing imidazole groups and Mg2+ ions "trapped" in Laponite, has been employed to develop an injectable self‐healing nanocomposite hydrogel. The properties and gelation mechanism of the hydrogel have been characterized and demonstrated by rheology, TEM, XRD, SEM, and NMR in particular. The hydrogel exhibits swift self‐healing performance without waiting for long time or elevated temperature. In particular, the present hydrogel can be applied in harsh alkaline environments, exhibiting a great advantage over traditional metal ion crosslinked hydrogels. The injectable self‐healing hydrogels based on the coordination interaction between Laponite and polymer have been rarely reported. Our research may make contributions not only to the design but also to the potential application of the hydrogels in a range of harsh alkaline environments, especially in enhanced oil recovery (EOR). [ABSTRACT FROM AUTHOR]

Periprosthetic wear debris‐induced aseptic loosening brings great pain to patients undergoing total joint arthroplasty. Tumor necrosis factor α (TNF‐α) is a pivotal cytokine involved in wear debris‐induced aseptic inflammation and subsequent osteolysis. Herein, we developed an injectable hydrogel system containing etanercept (ETN), a TNF‐α antagonist, to inhibit wear debris‐induced osteolysis. A set of thermosensitive poly(lactide‐co‐glycolide)‐b‐poly(ethylene glycol)‐b‐poly(lactide‐co‐glycolide) (PLGA–PEG–PLGA) copolymers with comparable molecular weights but different LA/GA molar ratios were synthesized by us, and their aqueous solutions presented sol‐to‐gel transitions along with the elevation of temperature. The LA/GA ratio not only impacted the phase transition temperature but also controlled the degradation rate of gel in vivo. The hydrogel with an appropriate in vivo degradation rate was employed to load and deliver ETN, and the drug introduction did not influence on its thermo‐induced gelation behavior. The loaded ETN was released from the gel depot in vitro in a sustained manner for up to 30 days. In a mouse bone‐implanted air pouch model, a single injection of the hydrogel formulation and subsequent sustained release of active ETN efficiently neutralized TNF‐α, resulting in significant suppression of titanium particles‐induced aseptic inflammation and subsequent osteolysis, and the effect was pronouncedly superior to that of an ETN solution. [ABSTRACT FROM AUTHOR]

The temporomandibular joint (TMJ) is commonly affected during fundamental oral activities, reducing the quality of life. Herein, we synthesized a heparin‐conjugated poloxamer hydrogel (HEP) as a thermo‐responsive injectable hydrogel for the treatment of TMJ disorders. While the gelation temperature of synthesized HEP (25% [w/v]) was 29.8–30.0°C, there was a slight difference between loss and storage modulus. HEP decreased the friction of the TMJ, thus requires less energy during load‐bearing jaw movement in comparison to POL. Moreover, the oscillation test dependent on strain ranges from 0.01% to 1000% validated that POL and HEP3 hydrogels showed a similar critical strain of about 5.6%. The total elastic recovery percentage of HEP3 (53.50%) was higher than POL (45.55%), indicating a better recovery of the deformed hydrogel structure. Along with the suitable viscoelastic properties for temporomandibular cavity, both hydrogels increased the proliferation of fibroblasts (L929) and chondrocytes (ATDC5) (cell viabilities were above 100%). However, newly synthesized HEP induced differentiated cell proliferation of chondrogenic cells at increasing concentrations up to 0.0156 mg/mL (p < 0.0001) compared to POL and the control group. The promising rheological properties and effects on chondrogenic cell proliferation of injectable heparin‐conjugated hydrogel make them candidates for intra‐articular injections used for the treatment of TMJ. [ABSTRACT FROM AUTHOR]

Autologous tumor cell vaccine is an individualized tumor treatment strategy to elicit tumor‐specific immune responses. However, it is difficult to exert efficacy in "cold" tumors, which lack tumor‐infiltrating T cells and are not sensitive to immunotherapy. Here, a dendritic cells (DCs) activation hydrogel is constructed based on bifunctional fusion membrane nanoparticles (FM‐NPs) composed of autologous tumor cell membranes and Mycobacterium phlei membrane extracts. The FM‐NPs not only provide tumor antigens but also can activate DCs. Afterward, the FM‐NPs are loaded in an injectable alginate hydrogel together with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). GM‐CSF releases rapidly and recruits DCs to hydrogel, while FM‐NPs retain in hydrogel to continuously interconnected with DCs, enriching mature DCs loaded with tumor antigens. In the 4T1 mouse breast tumor model, this hydrogel promotes the maturation of DCs in tumor‐draining lymph nodes and induces sufficient effector memory T cells that migrate to the tumor microenvironment. This successfully converts the "cold" tumors to "hot", thus exerting a significant antitumor effect synergized with the PD‐1 antibody. It is also verified the inhibitory effect of FM‐NPs using human gastric cancer organoids. Altogether, these findings demonstrate the application potential for the bifunctional fusion membrane‐based hydrogel as an autologous tumor vaccine by activating DCs. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells derived from adipose tissue have become a widely investigated cell source to use in tissue engineering applications. However, an optimal delivery scaffold for these cells is still needed. A rapidly gelling, injectable chitosan sponge was proposed in this study as a potential candidate for a suitable delivery scaffold. The results demonstrated the ability to encapsulate the stem cells at a 97.6% encapsulation efficiency and that the cells maintain their viability within the sponge. With the potential of using this scaffold for bone tissue engineering, ALP activity assay and fluorescent imaging for osteocalcin proved the ability to differentiate the encapsulated cells into the osteogenic lineage. Furthermore, co‐encapsulation of pyrophosphatase within the sponge was investigated as a method to overcome the inhibitory effects that the sponge degradation by‐products have on mineralization. Alizarin Red S staining demonstrated the beneficial effects of adding pyrophosphatase, where a significant increase in mineralization levels was achieved. [ABSTRACT FROM AUTHOR]

The development of biologically active multifunctional hydrogel wound dressings can assist effectively to wound regeneration and also has influenced multiple functions on wound injury. Herein, we designed a carbon‐based composited injectable silk fibroin hydrogel as multifunctional wound dressing to provide effective anti‐bacterial, cell compatibility and in vivo wound closure actions. Importantly, the fabricated injectable hydrogel exhibit sustained drug delivery properties, anti‐oxidant and self‐healing abilities, which confirm that composition of hydrogel is highly beneficial to tissue adhesions and burn wound regeneration ability. Frequently, designed injectable hydrogel can be injected into deep and irregular burn wound sites and would provide rapid self‐healing and protection from infection environment with thoroughly filled wound area. Meanwhile, incorporated carbon nanofillers improve injectable hydrogel strength and also offer high fluid uptake to hydrogel when applied on the wound sites. In vitro MTT cytotoxicity assay on human fibroblast cell lines establish outstanding cytocompatibility of the injectable hydrogel and also have capability to support cell growth and proliferations. In vivo burn wound animal model results demonstrate that the hydrogel dressings predominantly influenced enhanced wound contraction and also promoted greater collagen deposition, granulation tissue thickness and vascularization. This investigation's outcome could open a new pathway to fabricate multifunctional biopolymeric hydrogel for quicker burn wound therapy and effectively prevents microenvironment bacterial infections. [ABSTRACT FROM AUTHOR]

Methylglyoxal (MG) is a highly reactive dicarbonyl and the main precursor of advanced glycation end‐products (AGEs). After myocardial infarction (MI), MG‐derived AGEs accumulate in the heart and contribute to adverse remodeling and loss of cardiac function. In this study, the flavonoid fisetin, a dicarbonyl scavenger, is used to reduce the negative effects of MG in the post‐MI heart. A fisetin‐loaded collagen type I hydrogel (fisetin‐HG) is injected intramyocardially in mice at 3 h post‐MI, and compared to fisetin‐alone, hydrogel‐alone, or saline treatment. Fisetin‐HG treatment increases the level of glyoxalase‐1 (the main MG‐metabolizing enzyme), reduces MG‐AGE accumulation, and decreases oxidative stress in the MI heart, which is associated with smaller scar size and improved cardiac function. Treatment with fisetin‐HG also promotes neovascularization and increases the number of pro‐healing macrophages in the infarct area, while reducing the number of pro‐inflammatory macrophages. Taken together, the results demonstrate that the fisetin‐collagen hydrogel therapy can reduce the accumulation and negative effects of MG post‐MI. This therapy may be a promising approach to limit adverse cardiac remodeling, prevent damage, and preserve function of the infarcted heart. [ABSTRACT FROM AUTHOR]

Stimulus‐sensitive drug delivery materials are of vital significance to modern therapeutic technology. In particular, glucose‐responsive hydrogels capable of biomimetic release of hypoglycemic drugs according to glucose concentrations are one of the current research hotspots. In this paper, an injectable, glucose‐induced disintegrated natural‐polysaccharide‐based hydrogel with good self‐healing ability and biocompatibility is reported. The glucose‐responsiveness of the hydrogel stems from the reversible phenylborate ester bonds. The glucose‐triggered disintegration and insulin release are demonstrated in the hydrogel in a physiological environment. The two polymers produced by the disintegration of the hydrogel have good biocompatibility and biodegradability. Therefore, the hydrogel is considered to result in the development of smart insulin delivery systems. [ABSTRACT FROM AUTHOR]

Mandibular osteomyelitis (OM) is a challenging disease. Our objective was to assess a new OM model in rabbits induced by arsenic trioxide and to assess the efficacy of local treatment of OM using injectable gentamicin‐collagen hydrogels (GNT‐COLL). OM was induced unilaterally by controlled confinement of arsenic trioxide paste to the root canal of lower incisors of rabbits, while OM progression was characterized for 16 weeks. On the other hand, two injectable COLL hydrogels functionalized with GNT were prepared and characterized for physicochemical properties; a simple GNT‐COLL and a nanohydroxyapatite (nHA)‐ loaded hydrogel (GNT‐COLL/nHA). The two hydrogels were evaluated to treat OM model, while a multidose intramuscular GNT solution served as positive control. Outcomes were assessed by standard methods at 4 and 12 weeks post‐surgery. The clinical, radiographical, and histopathological findings provided evidence for the validity of the arsenic‐induced OM. The results demonstrated that a single intra‐lesional injection of the two hydrogels was more suppressive to OM compared to multidose systemic GNT. The composite GNT‐COLL/nHA hydrogel proved to induce early preservation of alveolar bone (ridge) length and higher amount of bone area\total area at 4 weeks (40.53% ± 2.34) followed by GNT‐COLL (32.21% ± 0.72). On the other hand, the positive control group revealed the least ridge length and bone area\total area (26.22% ± 1.32) at 4 weeks. Both hydrogels successfully arrested OM with no signs of recurrence for up to 12 weeks. Therefore, results support the greater advantages of the composite hydrogel as an osteogenic/antibiotic delivery system in OM treatment. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM) is the most prevalent primary intraocular malignant tumor with a high lethal rate. Patients who undergo conventional enucleation treatments consistently suffer permanent blindness, facial defects, and mental disorders, therefore, novel therapeutic modalities are urgently required. Herein, an injectable and stimuli‐responsive drug delivery antibacterial hydrogel (CP@Au@DC_AC50) is constructed via a facile grinding method that is inspired by the preparation process of traditional Chinese medicine. The incorporation of gold nanorods can enhance the mechanical strength of the hydrogel and realize photothermal therapy (PTT) and thermosensitive gel‐sol transformation to release the gene‐targeted drug DC_AC50 on demand in response to low‐density near‐infrared (NIR) light. The orthotopic model of UM is built successfully and indicates the excellent efficiency of CP@Au@DC_AC50 in killing tumors without damage to normal tissue because of its synergistic mild temperature PTT and gene‐targeted therapy. Moreover, the eyeball infection model reveals the remarkable antibacterial properties of the hydrogel which can prevent endophthalmitis in the eyeball. There is negligible difference between the CP@Au@DC_AC50+NIR group and normal group. This NIR light‐triggered gene‐targeted therapy/PTT/antibacterial treatment pattern provides a promising strategy for building multifunctional therapeutic platform against intraocular tumors and exhibits great potential for the clinical treatment of UM. [ABSTRACT FROM AUTHOR]

This study aimed at designing and fabrication of a novel injectable and thermosensitive melatonin‐loaded pluronic/chitosan hydrogel containing gold nanoparticles (GNPs) and poly glycerol sebacate (PGS) for myocardial tissue engineering. The PGS nanoparticles were used as the melatonin (drug model) carrier. The gelation time, syringeability, stability, and swelling of the hydrogel were scrutinized. Rheological properties, chemical composition, and morphology of the samples were also investigated. The effect of GNPs addition on the electrical conductivity of hydrogel was assessed. The cytotoxicity of hydrogels was assessed through MTT assay in the exposure of H9C2 cells up to 7 days. Scanning electron microscopy was applied to evaluate the morphology of seeded cells. The synthesis parameters of PGS nanoparticles were optimized through which 2.5%w/v of PGS and 1:10 organic phase to aqueous phase (O/A) ratio were found desirable. The optimum hydrogel illustrated 2 min gelation time and was stable up to 20 days with 5% swelling in the first 12 h into phosphate buffered saline. The GNPs with a uniform distribution rendered the hydrogel electrically conductive (1500 μS/cm). According to the MTT assay results, 3.125 μM melatonin was considered as the suitable concentration by which a significant increase in the cell viability was observed. The results exhibited that the prepared hydrogel composed of pluronic/chitosan/GNPs, and 3.125 μM melatonin‐loaded PGS nanoparticles could be applied as a promising scaffold for myocardial tissue engineering. [ABSTRACT FROM AUTHOR]

Introduction: Therapies for substrate‐related arrhythmias include ablation or drugs targeted at altering conductive properties or disruption of slow zones in heterogeneous myocardium. Conductive compounds such as carbon nanotubes may provide a novel personalizable therapy for arrhythmia treatment by allowing tissue homogenization. Methods: A nanocellulose carbon nanotube‐conductive hydrogel was developed to have conduction properties similar to normal myocardium. Ex vivo perfused canine hearts were studied. Electroanatomic activation mapping of the epicardial surface was performed at baseline, after radiofrequency ablation, and after uniform needle injections of the conductive hydrogel through the injured tissue. Gross histology was used to assess distribution of conductive hydrogel in the tissue. Results: The conductive hydrogel viscosity was optimized to decrease with increasing shear rate to allow expression through a syringe. The direct current conductivity under aqueous conduction was 4.3 × 10−1 S/cm. In four canine hearts, when compared with the homogeneous baseline conduction, isochronal maps demonstrated sequential myocardial activation with a shift in direction of activation to surround the edges of the ablated region. After injection of the conductive hydrogel, isochrones demonstrated conduction through the ablated tissue with activation restored through the ablated tissue. Gross specimen examination demonstrated retention of the hydrogel within the tissue. Conclusions: This proof‐of‐concept study demonstrates that conductive hydrogel can be injected into acutely disrupted myocardium to restore conduction. Future experiments should focus on evaluating long‐term retention and biocompatibility of the hydrogel through in vivo experimentation. [ABSTRACT FROM AUTHOR]

Application of tissue‐derived extracellular matrix (ECM) biomaterials in the repair of the temporomandibular joint (TMJ) disc is a promising approach for the treatment of disc abrasion and perforation, particularly for the young patient population. Although decellularized ECM (dECM) scaffolds preserve tissue‐specific structures as well as biological and biomechanical properties, they require surgical implantation. To address this issue, we prepared porcine TMJ discs into decellularized ECM with serial detergent and enzyme treatments, and the TMJ disc‐derived ECM was then processed into hydrogels via pepsin digestion. The decellularization efficiency was assessed by quantification of the DNA and matrix component contents. The fibrous ultrastructure of the hydrogel was observed by scanning electron microscopy (SEM). Rheological characterization and mechanical properties were measured. in vitro experiments with costal chondrocytes ensured the cellular proliferative capacity and compatibility in the injectable disc‐derived ECM hydrogel. The results showed that a large amount of DNA (>95%) was removed after decellularization; but, the collagen was retained. SEM of the hydrogels demonstrated a multiaperture fiber ultrastructure. Rheological studies revealed a rapid gelation temperature (37°C) and injectable properties. The mechanical properties of the hydrogels were adjusted by changing the ECM concentration. The in vitro studies revealed that the hydrogels are not cytotoxic, but instead showed good cytocompatibility. The hydrogel also showed good injectability and degradability through an in vivo study. Overall, these results suggest the great potential of injectable disc‐derived hydrogels for TMJ disc repair and regeneration applications. [ABSTRACT FROM AUTHOR]

Cartilage tissue engineering is the interdisciplinary science that will help to improve cartilage afflictions, such as arthrosis, arthritis, or following joints traumatic injuries. In the present work, we developed an injectable hydrogel which derived from decellularized extracellular matrix of sheep cartilage. Successful decellularization was evaluated by measuring the DNA, glycosaminoglycans (GAG), collagen contents, and histological analyses. There was a minor difference in GAG and collagen contents among natural cartilage and decellularized tissue as well as ultimate hydrogel. Rheological analysis showed that the temperature and gelation time of prepared hydrogel were 37°C and between 5 and 7 min, respectively. Mechanical properties evaluation indicated a storage modulus of 20 kPa. The results show that prepared hydrogel possessed cell‐friendly microenvironment as confirmed via calcein staining and MTT assay. Also, cells were able to proliferate which observed by H&E and alcian blue staining. Cell attachment and proliferation at the surface of the decellularized hydrogel was apparent by Scanning Electron Microscope (SEM) images and microphotographs. Furthermore, the cells embedded within the hydrogel were able to differentiate into chondrocyte with limited evidence of hypertrophy and osteogenesis in utilized cells which proved by SOX9, CoL2, ACAN, and also CoL1 and CoL10 gene expression levels. In summary, the results suggest that developed novel injectable hydrogel from decellularized cartilage could be utilized as a promising substrate for cartilage tissue engineering applications. [ABSTRACT FROM AUTHOR]

Fibrin glue has been widely used as a surgical sealing and hemostatic agent. Its application is restricted due to poor tissue adhesion and low mechanical strength. To develop better tissue sealant and hemostatic agent, this study prepared the injectable hydrogels by chemically cross‐linking gelatin (G) with or without hyaluronic acid (HA) in situ at a mild condition. The rheological analysis, Fourier transform infrared spectroscopy, swelling, proteolytic degradation, biocompatibility, tissue sealing, and hemostatic ability of the hydrogels were investigated. It was found that the chemical cross‐linking rapidly formed in both self‐crosslinking gelatin (sc‐G) and gelatin/hyaluronate acid (G/HA) hydrogels. The hydrogels could be degraded by trypsin and had a desirable biocompatibility. The tissue sealing ability of the hydrogels was superior to fibrin glue. Furthermore, the G/HA hydrogel had similar hemostatic performance as fibrin glue, and was better than that of gelatin hydrogel. The results in the study indicated that the G/HA hydrogel could be used in clinic as a tissue sealant or surgical hemostat. [ABSTRACT FROM AUTHOR]

A novel voriconazole (VCZ)‐loaded injectable hydrogel was in situ synthetized via a Schiff base reaction between polyaldehyde dextran (PAD) and carboxymethyl chitosan (CMCTS) for intraocular drug loading and release. Water‐insoluble VCZ, which is an effective agent in clinic treating fungal endophthalmitis, was loaded through the inclusion into the β‐cyclodextrin (β‐CD) cavity based on host‐guest interaction on the linear poly β‐CD chain, which was in situ twined in the cross‐linked hydrogel structure. The gelation time, degradation, and drug release process were investigated by studying three kinds of hydrogels with different volume ratio of PAD to CMCTS resolving in phosphate buffered saline (PBS) solution (3:7, 6:7, 9:7), respectively. The property of VCZ‐loaded injectable hydrogel should be adjusted through changing the cross‐linked density of the hydrogel, the molecular weight or concentration of the linear poly β‐CD to meet the treating requirement, and a multistage drug controlled‐release mechanism was proposed. In conclusion, the VCZ‐loaded in situ injectable hydrogel should be offered as a promising strategy for intraocular drug delivery in vitreous cavity for the treatment of fungal endophthalmitis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1909–1916, 2019. [ABSTRACT FROM AUTHOR]

Although significant progress has been made in the design and application of injectable hydrogels for biomedical applications, concurrent control of rheological and mechanical properties of injectable hydrogels has remained as an open challenge to the researchers. In this work, we introduce and put into practice a photo‐curable poloxamer (also known as Pluronic)/graphene oxide (Plu/GO) injectable hydrogel with well‐controlled rheological and mechanical properties. Acrylate group was anchored to hydrogel structure to endow photo‐crosslinking ability through decelerating degradation rate of poloxamer hydrogels after injection. It was found that the modified Plu remains stable in biological media for a long‐term period without significant weight loss. Rheological properties of hydrogels were also carried out as essential prerequisite for an ideal injectability via frequency sweep, flow curve, recovery, and yield stress before and after modification, signifying shear‐thinning behavior of Plu/GO hydrogels with high recoverability. The viscosity of shear‐thinning‐like hydrogels dropped at higher shear stress, which facilitated injection process. Moreover, mechanical behavior of Plu was optimized by manipulating the content of Plu, degree of modification with reactive precursor, curing, and particularly incorporation of GO without deteriorating effects on rheological behavior of Plu. [ABSTRACT FROM AUTHOR]

The worldwide incidence of bone disorders is raising, mainly due to aging population. The lack of effective treatments is pushing the development of synthetic bone substitutes (SBSs). Most ceramic-based SBSs commercially available display limited handling properties. Attempting to solve these issues and achieve wider acceptance by the clinicians, granular ceramics have been associated with hydrogels (HGs) to produce injectable/moldable SBSs. Dextrin, a lowmolecular- weight carbohydrate, was used to develop a fully resorbable and injectable HG. It was first oxidized with sodium periodate and then cross-linked with adipic acid dihydrazide. The in vivo biocompatibility and safety of the dextrin-based HG was assessed by subacute systemic toxicity and skin sensitization tests, using rodent models. The results showed that the HG did not induce any systemic toxic effect, skin reaction, or genotoxicity, neither impaired the bone repair/regeneration process. Then, the HG was successfully combined with granular bone substitute, registered as Bonelike (250–500 μm) to obtain a moldable/injectable SBS, which was implanted in tibial fractures in goats for 3 and 6 weeks. The obtained results showed that HG allowed the stabilization of the granules into the defect, ensuring effective handling, and molding properties of the formulation, as well as an efficient cohesion of the granules. [ABSTRACT FROM AUTHOR]

To provide sustained release of exenatide and enhance therapeutic efficacy for the treatment of type 2 diabetes compared to the existing products for exenatide, we developed an exenatide‐loaded, redox‐active, injectable gel (Exe@RIG). This injectable gel is formed by a polyion complex (PIC) comprising three components, (1) cationic polyamine–poly(ethylene glycol)–polyamine triblock copolymer possessing reactive oxygen species (ROS)‐scavenging moieties as side chains, (2) anionic poly(acrylic acid), and (3) exenatide. The mixture formed exenatide‐loaded PIC flower micelles at room temperature, which immediately converted to a gel under physiological conditions. Owing to electrostatic interactions between exenatide and the PIC gel network, RIG was able to provide sustained release of exenatide without a significant initial burst. Subcutaneous injection of Exe@RIG once a week prevented the increase in glucose concentration significantly in db/db mice compared to those in control groups. In addition, Exe@RIG suppressed the degeneration of pancreatic islets, which is reported to be caused by increased ROS. Our result indicates that Exe@RIG has the potential to provide a long acting exenatide as well as enhanced efficacy in the treatment of type 2 diabetes compared to the existing products. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1107–1113, 2019. [ABSTRACT FROM AUTHOR]

Abstract: In this study, an injectable and thermo‐sensitive alginate/β‐tricalcium phosphate hydrogel (TSAH/β‐TCP) was prepared for aspirin release to a bone defect. Aspirin was dissolved into a mixture of poly(N‐isopropylacrylamide) (PNIPAAm), an aminated alginate‐g‐PNIPAAm co‐polymer, and β‐TCP powders. Scanning electron microscopy showed that TSAH/β‐TCP had an interconnected porous microstructure with a porosity of 86.78%. The cross‐linked hydrogel released approximately 40% of the aspirin in the first 3 days and then slowly released the remainder. At a low concentration (≤100 μg/mL), aspirin did not promote cell proliferation, but enhanced the alkaline phosphatase activity, and osteocalcin (OCN) and collagen I expression of human bone marrow‐derived mesenchymal stem cells. The TSAH/β‐TCP/aspirin hydrogel was injected into the periosteum of the rat cranial bone, and its in vivo bone‐forming ability was evaluated at 12 weeks. A bone morphogenetic protein 2 (BMP‐2)‐loaded TSAH/β‐TCP hydrogel was injected as a control. Micro‐computed tomography showed that the percentage of mineralized tissue in the TSAH/β‐TCP/BMP‐2 and TSAH/β‐TCP/aspirin groups were similar and significantly higher than that in the TSAH/β‐TCP group. Immunohistochemical staining showed considerable expression of OCN, especially in the TSAH/β‐TCP/BMP‐2 and TSAH/β‐TCP/aspirin groups. These results suggest that the injectable TSAH/β‐TCP/aspirin hydrogel has great potential for bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1739–1751, 2018. [ABSTRACT FROM AUTHOR]

In this work, a versatile and simple strategy to build an injectable interpenetrating polymer network (IPN) hydrogel with tunable mechanical properties and self-healing ability is reported. The gelation time and mechanical properties can be tuned by pH or the solid content. Due to the exchange of acylhydrazone and boronate ester bonds formed between functionalized prepolymers, the hydrogels can self-heal at either acidic or basic condition. Furthermore, the pH-induced IPN to semi-IPN reversible transition endows the hydrogels with tunable pore structure and mechanical properties. It is hoped that this novel strategy will provide new opportunities in design and preparation of 3D-printable IPN hydrogels, fostering their use in a wide range of applications such as controlled drug release and tissue engineering. [ABSTRACT FROM AUTHOR]

An injectable dual redox responsive diselenide-containing poly(ethylene glycol) (PEG) hydrogel was successfully developed by combining the conceptions of injectable hydrogels and dual redox responsive diselenides. In the first step, four-armed PEG was modified with N-hydroxysuccinimide (NHS)-activated esters and thereafter, crosslinked by selenocystamine crosslinkers to form injectable hydrogels via the rapid reaction between NHS-activated esters and amino groups. The cross-sectional morphology, mechanical properties, and crosslinking modes of hydrogels were well characterized via scanning electron microscope (SEM), rheological measurements, and Fourier transform infrared spectra, respectively. In addition, the oxidation- and reduction-responsive degradation behaviors of hydrogels were observed and analyzed. The model drug, rhodamine B, was encapsulated in the hydrogel. The drug-loaded hydrogel exhibited a dual redox responsive release profile, which was consistent with the degradation experiments. The results of all experiments indicated that the formulated injectable dual redox responsive diselenide-containing PEG hydrogel can have potential applications in various biomedical fields such as drug delivery and stimuli-responsive drug release. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2451-2460, 2017. [ABSTRACT FROM AUTHOR]

Water-soluble poly(ethylene glycol) derivatives with multiple 'clickable' mercapto groups or double bonds were facilely synthesized in a large scale by direct polycondensation of oligo(ethylene glycol) diol with mercaptosuccinic acid or maleic acid catalyzed by scandium trifluoromethanesulfonate under mild conditions. Injectable hydrogels containing doxorubicin hydrochloride (DOX · HCl) could be rapidly formed using these poly(ethylene glycol) derivatives as precursors via in situ thiol-ene 'click' reaction under physiological conditions without light, initiator, or metal catalyst. DOX · HCl could be sustained released from the hydrogels as a result of the hindrance of the three dimensional hydrogel network on the drug molecules, which makes this kind of DOX-loaded hydrogels a promising candidate for localized tumor chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The regenerative therapy of tissues relays on successful cell transplantation and engraftment. Soft hydrogel carriers are employed to protect transplanted cells from harmful microenvironment in soft tissue regeneration. Herein an injectable, porous, biodegradable, bioresorbable, and elastomeric hydrogel fabricated from poly(propylene fumarate-co-sebacate-co-ethylene glycol) crosslinked with PEGDA for cardiomyoblast encapsulation was reported. The hydrogel retains adequate mechanical property in the range of native myocardium even after 30 days of degradation (49 ± 0.008 kPa). The hydrogel shows maximum extensibility without collapsing even under 60% compression. The hydrogel retains 70.58% equilibrium water content, wide internal porosity, and slow bulk degradation favorable for cell carriers. The cardiomyoblast cells encapsulated in hydrogel retains viability even after 30 days of culture. The long-term viability and proliferation studies of encapsulated cells in the hydrogel substantiate the suitability of hydrogel microenvironment for cell survival. The present hydrogel is a potential cell carrier with favorable physical and biological properties for cell encapsulation for cardiac applications. The candidate hydrogels perform better than the other reported elastomeric hydrogels fabricated for cell therapy. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2936-2944, 2016. [ABSTRACT FROM AUTHOR]

Chitosan-thermosensitive hydrogels present interesting features for the embolization of blood vessels, but need to be better characterized and optimized. Chitosan polymer (degree of deacetylation (DDA) of 94%) was purified and combined with Visipaque (VIS), a nonionic isotonic contrast agent composed of iodixanol. A beta-glycerolphosphate (βGP) solution was then added to induce gelation at body temperature. The gelation process was monitored by rheometry, measuring the evolution of the sample storage ( G′) and loss ( G″) moduli as a function of VIS and βGP concentration. Adding VIS significantly slowed down gelation kinetics, but a 12% and higher βGP concentration provided a radiopaque solution, which at 37°C, gels immediately. A custom-made in vitro embolization bench test was developed to assess the gel's occlusive properties, and its injectability through a small diameter catheter was verified. Results show that the short-term occlusive properties of the gel were insufficient when using a βGP concentration of 12% w/v (about 0.4 M), but that increasing the βGP to 20% (0.6 M) allowed an acceleration of the gelation and the immediate blocking of flow above physiological pressure. The contrast agent was rapidly released in solution, such that it would not interfere with future follow-up imaging. In accordance with the literature data, the cytotoxicity of gel extracts increased with βGP concentration and to a lesser extent with VIS concentration. Preliminary in vivo testing showed easy injection by catheter and good visibility under fluoroscopy. These results suggest that radiopaque CH/βGP20%/VIS hydrogels present significant potential as embolizing agents for blood vessels and aneurysms. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1551-1562, 2016. [ABSTRACT FROM AUTHOR]