Search

For the first time, functionalized okra gum with multi-aldehyde groups (OG-CHO) and carboxymethyl chitosan (CMCh) is used to create injectable hydrogels (IHs) via Schiff base reaction at 37 °C. Gelation time is optimized based on the ratio of aldehyde groups of OG-CHO to amine groups of CMCh (9 ± 3 to 2 ± 1 min). Physical characteristics such as gel content (84 ± 2) and porosity (66 ± 3) are assessed. The syringeability, injectability, and self-healing properties are evaluated qualitatively and quantitatively using a rheometer. Structural analysis is carried out by FT-IR and 1H-NMR spectroscopy, while surface morphology and pore size (80 ± 5 µm) are examined via SEM. The swelling ratio is studied in the gel state of the IH in phosphate buffer saline (PBS) at varying pH levels of 5.5, 7.4, and 8.5, revealing a decrease in swelling ratio with increasing pH from 5.5 to 7.4 (75 ± 24 to 635 ± 20%), followed by an increase in swelling at pH 8.5 (724 ± 18.5%). Ciprofloxacin is employed as a model drug for release assays, and drug release behavior in gel forms of IH across different wound pH ranges is evaluated. The swelling and drug release behavior is described using the Korsmeyer–Peppas model, which shows non-Fickian diffusion. Furthermore, biocompatibility (cell viability > 90%), antibacterial assay, and in vitro degradation (~ 98%) are also assessed. [ABSTRACT FROM AUTHOR]

The current study aims to prepare and compare three injectable hydrogels consisting of chitosan, hyaluronic acid, and hydroxyapatite in different combinations using two solvents and homoginizer that can be employed in bone tissue engineering (BTE) for remodelling and healing bones. The hydrogel structures were well characterized by FT-IR, XRD and SEM analyses. Surface study, porosity, percolation capacity, bone cell adhesion and proliferation, and swelling properties were tested and was found that these hydrogels are better candidates for BTE. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) analysis showed better compatibility with mononuclear cells derived from human peripherals. Our findings suggest that these hydrogels can be efficiently used as injectable hydrogels in BTE applications. [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]

Osteoarthritis (OA) is the most prevalent chronic joint disorder and is a major cause of disability among the elderly population. The degeneration and damage of articular cartilage associated with OA can result in a diminished range of motion in joints, subsequently impacting fundamental activities such as ambulation, standing, and grasping objects. In severe cases, it may culminate in disability. Traditional pharmacological treatments are often accompanied by various side effects, while invasive surgical procedures increase the risk of infection and thrombosis. Consequently, identifying alternative new methods for OA treatment remains a formidable challenge. With advancements in responsive hydrogel drug delivery platforms, an increasing number of strategies have emerged to enhance OA treatment protocols. Injectable response hydrogel drug delivery platforms show many advantages in treating OA, including improved biocompatibility, prolonged drug release duration, elevated drug loading capacity and enhanced sensitivity. This article reviews the recent progress of injectable responsive hydrogel drug delivery platform for OA treatment over the past few years. These innovative methodologies present new strategies and directions for future OA treatment while summarizing a series of challenges faced during the clinical transformation of injectable response hydrogel drug delivery platforms. Overall, injectable responsive hydrogel drug delivery platforms show great potential in treating OA, especially regarding improving drug retention time and stimulus-responsive release at the lesion sites. These innovative methods provide new hope for future OA treatment and point the way for clinical applications. [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]

Photodynamic therapy (PDT) has been emerged as a promising modality for cancer treatment. However, the development of drug delivery system enabling continuous release of photosensitizers (PSs) for long-term PDT treatment still remains challenges. Herein, a H2O2-responsive injectable hydrogel, covalently crosslinked by N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diaminium (TSPBA) with PVA containing polythiophene quaternary ammonium salt (PT2) polymer dots (PDots) as a photosensitizer was fabricated. Under the stimulation of H2O2, the obtained injectable hydrogel gradually degrades and releases PDots. In vitro experiments suggested that the released PDots could realize efficient tumor cells inhibition through its robust singlet oxygen generation capability upon 577 nm laser irradiation. In vivo studies demonstrated a sustained retention of PDots for at least 7 days following single-dose administration, facilitating efficient tumor inhibition with light treatments for 3 times without apparent biotoxicity. This work presents an innovative polymer dots-based composite local drug delivery system for long-term PDT in cancer treatment. [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]

Acute kidney injury (AKI) constitutes a severe condition characterized by a sudden decrease in kidney function. Utilizing lineage-restricted stem/progenitor cells, directly reprogrammed from somatic cells, is a promising therapeutic option in personalized medicine for serious and incurable diseases such as AKI. The present study describes the therapeutic potential of induced nephron progenitor cell-sourced molecules (iNPC-SMs) as a cell-free strategy against cisplatin (CP)-induced nephrotoxicity, employing hyaluronic acid (HA) hydrogel-mediated local delivery to minimize systemic leakage and degradation. iNPC-SMs exhibited anti-apoptotic effects on HK-2 cells by inhibiting CP-induced ROS generation. Additionally, the localized biodistribution facilitated by hydrogel-mediated iNPC-SM delivery contributed to enhanced renal function, anti-inflammatory response, and renal regeneration in AKI mice. This study could serve as a 'proof of concept' for injectable hydrogel-mediated iNPC-SM delivery in AKI and as a model for further exploration of the development of cell-free regenerative medicine strategies. [ABSTRACT FROM AUTHOR]

Hydrogels have garnered significant interest in the biomedical field owing to their tissue-like properties and capability to incorporate various fillers. Among these, injectable hydrogels have been highlighted for their unique advantages, especially their minimally invasive administration mode for implantable use. These injectable hydrogels can be utilized in their pristine forms or as composites by integrating them with therapeutic filler materials. Given their primary application in implantable platforms, enzymatically crosslinked injectable hydrogels have been actively explored due to their excellent biocompatibility and easily controllable mechanical properties for the desired use. This review introduces the crosslinking mechanisms of such hydrogels, focusing on those mediated by horseradish peroxidase (HRP), transglutaminase (TG), and tyrosinase. Furthermore, several parameters and their relationships with the intrinsic properties of hydrogels are investigated. Subsequently, the representative biomedical applications of enzymatically crosslinked-injectable hydrogels are presented, including those for wound healing, preventing post-operative adhesion (POA), and hemostasis. Furthermore, hydrogel composites containing filler materials, such as therapeutic cells, proteins, and drugs, are analyzed. In conclusion, we examine the scientific challenges and directions for future developments in the field of enzymatically crosslinked-injectable hydrogels, focusing on material selection, intrinsic properties, and filler integration. [ABSTRACT FROM AUTHOR]

In recent years, injectable hydrogels and cardiac patches have provided a promising approach to improve cardiac regeneration and function after myocardial infarction, however, the crucial designing factors of these biomaterials have been less reviewed. Therefore, in this review, we speculate on the prominent design parameters. A profound understanding of the main properties of native heart tissue can guide the efforts to obtain biomaterials with desirable biomimicking properties that improve the effectiveness of future fabricated myocardial biomaterials. Moreover, the injectable hydrogels and cardiac patches with reactive oxygen species scavenging properties will be reviewed in detail owing to the promising results of in vitro and in vivo studies on cardiac regeneration after myocardial infarction. This review can pave the way for an optimized design for effective cardiac biomaterials by considering the optimum ranges for physical, chemical, and biological characteristics of biomaterials, as well as the study of undetected parameters that can be investigated in future studies. [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]

Hydrogel stands out as one of the most attractive wound dressings due to its excellent moisturizing properties and capacity to absorb wound exudates. However, conventional hydrogel dressings often lack responsiveness to the microenvironment, merely acting as protective barriers for the wound. Consequently, they exhibit limited effectiveness in preventing infection and facilitating wound repair. To address these problems, we have developed a multifunctional injectable hydrogel, CF/MS@HG, based on peroxidase-like nanozymes, aiming at rapidly healing bacterial-infected wounds. The hydrogel is mainly composed of oxidized sodium alginate, aminated gelatin, and polylysine, encapsulating MIL-101(CuFe) NPs (CF) and manganese selenide nanoparticles (MnSe2 NPs, or MS NPs). After injection, the complex rapidly gelatinizes at the infected wound site through a Schiff base reaction. In vitro experiments have demonstrated the hydrogel's strong adhesion and self-healing capabilities. Moreover, CF exhibiting peroxidase (POD)-like activity, catalyzes in situ hydrogen peroxide (H2O2) to generate highly toxic hydroxyl radicals (·OH) within the wound microenvironment, inducing oxidative damage to bacteria. Meanwhile, MS decomposes into H2Se in the slightly acidic wound microenvironment, disrupting bacterial metabolism and inhibiting proliferation. The addition of polylysine further enhances the hydrogel's antibacterial properties. In vivo experiments have shown that the hydrogel exhibits excellent biological safety and significantly promotes wound healing. This multifunctional smart hydrogel holds great promise for the treatment of bacterial-infected wounds. [ABSTRACT FROM AUTHOR]

Developing hydrogels with excellent 3D printability, injectability, and mechanical integrity presents an imposing challenge in biomaterials research, especially in the biomedical field where biocompatibility is crucial. This study involved the development of 3D printable and injectable polysaccharide-based hydrogels with inherent self-healing capabilities. Carboxymethyl chitosan and quaternized chitosan (QCS) functioned as polymer backbones, reinforced by dialdehyde-cellulose nanocrystals (DACNC) as a cross-linker. Here, the concentrations of QCS and DACNC were adjusted and optimized for ideal performance. The cross-linking process was orchestrated in situ, integrating dynamic hydrogen bonds and Schiff base covalent bonds to achieve a multi-cross-linked hydrogel network. Comprehensive characterization of the material, including rheological measurements and macroscopic evaluations, demonstrated the hydrogel's admirable injectability, printability, and self-healing attributes. In vitro cell viability assessments on human dermal fibroblasts revealed favorable biocompatibility and minimal cytotoxicity of the hydrogels, properties influenced by the concentrations of QCS. The obtained hydrogels exhibit promising attributes suitable for fabricating 3D printable and injectable hydrogel customized for biomedical applications, particularly wound healing. [ABSTRACT FROM AUTHOR]

Copyright of Polymer Materials Science & Engineering is the property of Sichuan University, Polymer Research Institute and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Conventional pulp capping materials have limited anti-inflammatory capacity. It is necessary to develop more effective pulp capping material for the treatment of inflamed pulps. Tannic acid (TA) is a natural, water-soluble polyphenol with antimicrobial and anti-inflammatory properties. This study aimed to investigate the effects of a tannin-containing hydroxypropyl chitin hydrogel (HPCH/TA hydrogel) as an innovative pulp capping material. The physicochemical properties of the composite hydrogels were characterized. The effects of HPCH/TA hydrogel as a pulp capping material were evaluated in vitro and in vivo. The underlying mechanism of the anti-inflammatory effects of HPCH/TA hydrogel was explored. The HPCH/TA hydrogel demonstrated favorable temperature sensitivity, injectability, and antibacterial properties. In vitro, the HPCH/TA hydrogel effectively promoted the proliferation of human dental pulp cells and inhibited interleukin-1β, interleukin-6, and tumor necrosis factor-α expression, possibly by suppressing the nuclear factor kappa-B pathway. In vivo, on the fourth day after capping, the HPCH/TA hydrogel group showed lower inflammatory scores compared to the control and iRoot BP Plus (commercial pulp capping material) group. By the sixth week, complete reparative dentin formation was observed in the HPCH/TA hydrogel group, with no difference in thickness compared to the iRoot BP Plus group. Collectively, the HPCH/TA hydrogel holds promise as a bioactive pulp capping material for promoting the repair of inflamed pulp in vital pulp therapy. [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]

Irreversible fibrosis following myocardial infarction (MI) stiffens the infarcted myocardium, which remains challenging to restore. This study aimed to investigate whether the injectable RLP12 hydrogel, derived from recombinant resilin protein, could serve as a vehicle for stem cells to enhance the function of the infarcted myocardium. The RLP12 hydrogel was prepared and injected into the myocardium of rats with MI, and brown adipose-derived mesenchymal stem cells (BADSCs) were loaded. The survival and differentiation of BADSCs in vivo were investigated using immunofluorescence one week and four weeks after treatment, respectively. The heart function, MI area, collagen deposition, and microvessel density were further assessed four weeks after treatment through echocardiography, histology, immunohistochemistry, and immunofluorescence. The RLP12 hydrogel was prepared with a shear modulus of 10–15 kPa. Four weeks after transplantation, the RLP12 hydrogel significantly improved cardiac function by increasing microvessel density and reducing infarct area size and collagen deposition in MI rats. Furthermore, the distribution ratio of collagen III to I increased in both the centre and edge areas of the MI, indicating the improved compliance of the infarct heart. Moreover, the RLP12 hydrogel also promoted the survival and differentiation of BADSCs into cardiac troponin T- and α-smooth muscle-positive cells. The RLP12 hydrogel can be utilised as an injectable vehicle of BADSCs for treating MI and regulating collagen I and III expression profiles to improve the mechanical microenvironment of the infarct site, thereby restoring heart function. The study provides novel insights into the mechanical interactions between the hydrogel and the infarct microenvironment. [ABSTRACT FROM AUTHOR]

Wound infections caused by Staphylococcus aureus often result in localized suppurative lesions that severely impede the healing process, so it is urgent to develop a dress with efficient antimicrobial and pro-healing functions. In this study, the bifunctional injectable hydrogel lactoferrin (Lf)/NZ2114/lithium magnesium silicate hydrogel (LMSH) was first successfully prepared through the electrostatic interaction method. The physical, biological, and efficacy properties are systematically analyzed with good shear-thinning capacity and biocompatibility. More importantly, it inhibits infection and promotes wound healing in a mouse wound infection model after 14 d treatment, and the bactericidal rate and healing rate were over 99.92% and nearly 100%, respectively. Meanwhile, the massive reduction of inflammatory cells, restoration of tissue structure, and angiogenesis in mice showed the anti-inflammatory and pro-healing properties of the hydrogel. The healed wounds showed thickening with more hair follicles and glands, suggesting that the hydrogel Lf/NZ2114/LMSH (Three in One) could be a better dressing candidate for the treatment of S. aureus-induced wound infections. [ABSTRACT FROM AUTHOR]

With the rising prevalence of diabetes, a growing number of patients are at high risk for chronic nonhealing wounds. These wounds are a severe complication of diabetes, associated with increased rates of infection, amputation, and mortality. Currently, there are no established clinical approaches for effectively treating diabetic wounds, resulting in a significant socioeconomic burden on both patients and healthcare systems. Diabetic wound healing is frequently hampered by excessive reactive oxygen species (ROS) biogenesis and unrestrained bacterial infection, with methicillin-resistant Staphylococcus aureus (MRSA) being a particularly aggressive pathogen in this setting. Polydopamine nanoparticles (PDA NPs) can readily scavenge ROS and facilitate efficient photoconversion. In this study, an injectable gelatin methacryloyl (GelMA)/PDA NPs hydrogel, designated GMP, was designed as an approach to overcoming these diabetic issues through the incorporation of PDA NPs into GelMA hydrogels. The prepared GMP hydrogel exhibited a porous 3D structure amenable to injection such that it can produce a hydrogel barrier that protects the wound site, rapidly providing hemostasis and absorbing wound-related exudates. GMP was then able to scavenge ROS and exert photothermal sterilizing effects, ultimately alleviating oxidative stress and eliminating bacteria from the site of wounding. This GMP hydrogel was also biocompatible with building blocks derived from natural materials. In vitro and in vivo, this GMP hydrogel containing PDA NPs was able to improve MRSA-infected diabetic wound healing, underscoring its value as a tool for the treatment of such wounds in a clinical setting. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is considered as a significant cause of death globally. Exosomes (EXOs) are essential for intercellular communication and pathophysiology of several cardiovascular diseases. Nevertheless, the short half-life and rapid clearance of EXOs leads to a lack of therapeutic doses delivered to the lesioned area. Therefore, an injectable silk fibroin and alginate (SF/Alg) composite hydrogel was developed to bind folate receptor-targeted EXOs (FA-EXOs) derived from H9C2 cells for the therapy of myocardial injury following myocardial infarction-ischemia/reperfusion (MI-I/R). The resulting composite exhibits a variety of properties, including adjustable gelation kinetics, shear-thinning injectability, soft and dynamic stability that adapts to the heartbeat, and outstanding cytocompatibility. After injected into the damaged rat heart, administration of SF/Alg + FA-EXOs significantly enhanced cardiac function as demonstrated by improved ejection fraction, fractional shortening and decreased fibrosis area. The results of real-time PCR and immunofluorescence staining show a remarkable up-regulation in the expression of proteins (CD31) and genes (VWF and Serca2a) related to the heart. Conversely, expression of fibrosis-related genes (TGF-β1) decreased significantly. Therefore, the obtained SF/Alg + FA-EXOs system remarkably enhanced the intercellular interactions, promoted cell proliferation and angiogenesis, and achieved an outstanding therapeutic effect on MI. [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]

Acute myocardial infarction (AMI) has been treated via injectable hydrogels and biomaterial patches invented using tissue engineering advancements over the past decade. Yet the curative potential of injectable hydrogels and stem cells is limited. Here, we propose the development of an injectable and conductive hydrogel composed of oxidised macromolecular hyaluronic acid and chitosan-grafted aniline tetramer polymeric components. In an attempt to enhance the therapeutic potential of AMI therapy, mesenchymal stem cells derived from human umbilical cord blood (HUCB-MSC) have been integrated into the formulation of a conductive hydrogel. For reliable connection to the beating hearts, the hydrogel exhibited suitable adhesive properties. Hydrogel's potent biocompatibility was determined by in vitro investigations of cell viability and proliferation of NRCMs and H9C2 cardiomyocytes. After myocardial injection, longer HUCB-MSCs survival length, cardiac functioning, and histology in SD rat myocardium were demonstrated, greatly associated by up-regulation and downregulation of cardiac-related relative gene expressions of angiogenic factors and inflammatory factors, respectively. The injectable hydrogel that contained HUCB-MSCs substantially enhanced the therapeutic benefits, indicating a potentially beneficial therapeutic approach to AMI therapy. [ABSTRACT FROM AUTHOR]

Peri-implantitis is an excessive inflammatory response induced by complex interactions between the bacteria, host immune system, and tissues around the dental implant. Alveolar bone resorption caused by peri-implantitis is a significant cause of implant failure. However, to restore the osteogenic microenvironment, a multifaceted therapeutic method that simultaneously encompasses anti-inflammatory and tissue regenerative strategies is indispensable. In this study, a temperature-sensitive hydrogel (FMXO) loaded with MXene and MgO was used to develop a multifunctional injectable MXene-based hydrogel. This hydrogel could release MXene and MgO in irregular bone defect areas in situ with no toxicity, either in vitro or in vivo. Our results showed that FMXO effectively inhibited the NF-κB signaling pathway in RAW264.7 cells and simultaneously upregulated the expression of ALP, Runx2, and OCN in bone marrow mesenchymal stromal cells (BMSCs). Therefore, FMXO exerted pharmacological effects on inflammation and bone regeneration. Moreover, we found that FMXO, when exposed to near-infrared (NIR) light, exhibited high efficacy against Porphyromonas gingivalis , Fusobacterium nucleatum , and their plaque microorganisms, which were considered the initiating factors of peri-implantitis. The multifunctionality of FMXO was also confirmed in an immediate peri-implant rat model in vivo, suggesting the great potential for peri-implantitis therapy in the dental clinic. [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]

Periodontitis is associated with several systemic diseases, and advanced periodontitis is often linked to an extensive inflammatory microenvironment and irregularly shaped alveolar bone defects. However, eliminating periodontal inflammation in a minimally invasive manner while repairing irregularly shaped bone defects is clinically challenging. In comparison to traditional bone grafts, a thermo-sensitive hydrogel can be injected into deep periodontal pockets, forming and filling the alveolar bone defects in situ. In this study, porous injectable thermo-sensitive hydrogels containing magnesium ions were prepared by adding magnesium particles (MPs) to a glycerophosphate solution and combining this mixture with a chitosan solution. The incorporation of MPs created interconnected pores in the hydrogel, exhibiting high cytocompatibility and maintaining cell viability, proliferation, spreading, and osteogenesis in vitro. Evaluation on an experimental periodontitis rat model, using microcomputed tomography and histological analyses, demonstrated that this Mg2+-containing hydrogel effectively reduced periodontal inflammation, inhibited osteoclast activity, and partially repaired inflammation-induced alveolar bone loss. These results suggest that Mg2+-containing thermo-sensitive porous hydrogels might be promising candidates for treating periodontitis. [ABSTRACT FROM AUTHOR]

The treatment adherence of narcotics-addicted individuals with reduced incidences of relapse can be enhanced by a sustained drug release formulation of antinarcotics. So far, different drug formulations have been reported with sustained drug release periods of 28 and 35 days. To further enhance this duration, different formulations of injectable hydrogels (IHs) have been developed by combining low molecular weight (LMW) and high molecular weight (HMW) chitosan (CS) with guar gum (GG) and crosslinking them by sodium bi phosphate dibasic. The structural, morphological, and physicochemical properties of LMW-CS IH, and HMW-CS IH were evaluated using Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA), scanning electron microscopy (SEM), and rheological, swelling, and biodegradation analysis. The HMW-CS IH showed high crosslinking, increased thermal stability, high mechanical strength, elevated swelling, and low biodegradation. The antinarcotic drugs naltrexone (NTX) and disulfiram (DSF) were loaded separately into the HMW-CS IH and LMW-CS IH. The release of NTX and DSF was investigated in phosphate buffer saline (PBS) and ethanol (0.3%, 0.4%, and 0.5%) over a 56-day period using an UV spectrophotometer. The drug release data were tested in zero-order, first-order, and Korsemeyer–Peppas mathematical models. In PBS, all prepared formulations followed non-Fickian drug release, while in ethanol, only NTX HMW-CS IH followed non-Fickian release in all three different concentrations of ethanol. [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]

Background: Elderly patients suffering from osteoporotic fractures are more susceptible to delayed union or nonunion, and their bodies then are in a state of low-grade chronic inflammation with decreased antioxidant capacity. Tanshinone IIA is widely used in treating cardiovascular and cerebrovascular diseases in China and has anti-inflammatory and antioxidant effects. We aimed to observe the antioxidant effects of Tanshinone IIA on mesenchymal stem cells (MSCs), which play important roles in bone repair, and the effects of local application of Tanshinone IIA using an injectable biodegradable hydrogel on osteoporotic fracture healing. Methods: MSCs were pretreated with or without different concentrations of Tanshinone IIA followed by H2O2 treatment. Ovariectomized (OVX) C57BL/6 mice received a mid-shaft transverse osteotomy fracture on the left tibia, and Tanshinone IIA was applied to the fracture site using an injectable hydrogel. Results: Tanshinone IIA pretreatment promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes, and inhibited H2O2-induced reactive oxygen species accumulation in MSCs. Furthermore, Tanshinone IIA reversed H2O2-induced apoptosis and decrease in osteogenic differentiation in MSCs. After 4 weeks of treatment with Tanshinone IIA in OVX mice, the bone mineral density of the callus was significantly increased and the biomechanical properties of the healed tibias were improved. Cell apoptosis was decreased and Nrf2 expression was increased in the early stage of callus formation. Conclusions: Taken together, these results indicate that Tanshinone IIA can activate antioxidant enzymes to protect MSCs from H2O2-induced cell apoptosis and osteogenic differentiation inhibition. Local application of Tanshinone IIA accelerates fracture healing in ovariectomized mice. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and it leads to irreversible inflammation in intra-articular joints. Current treatment approaches for RA include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, and biological agents. To overcome the drug-associated toxicity of conventional therapy and transdermal tissue barrier, an injectable NSAID-loaded hydrogel system was developed and explored its efficacy. Results: The surface morphology and porosity of the hydrogels indicate that they mimic the natural ECM, which is greatly beneficial for tissue healing. Further, NSAIDs, i.e., diclofenac sodium, were loaded into the hydrogel, and the in vitro drug release pattern was found to be burst release for 24 h and subsequently sustainable release of 50% drug up to 10 days. The DPPH assay revealed that the hydrogels have good radical scavenging activity. The biocompatibility study carried out by MTT assay proved good biocompatibility and anti-inflammatory activity of the hydrogels was carried out by gene expression study in RAW 264.7 cells, which indicate the downregulation of several key inflammatory genes such as COX-2, TNF-α & 18s. Conclusion: In summary, the proposed ECM-mimetic, thermo-sensitive in situ hydrogels may be utilized for intra-articular inflammation modulation and can be beneficial by reducing the frequency of medication and providing optimum lubrication at intra-articular joints. [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]

Endogenous stimuli-responsive injectable hydrogels hold significant promise for practical applications due to their spatio-temporal controllable drug delivery. Herein, we report a facile strategy to construct a series of in situ formation polypeptide hydrogels with thermal responsiveness and enzyme-triggered dynamic self-assembly. The thermo-responsive hydrogels are from the diblock random copolymer mPEG-b-P(Glu-co-Tyr). The L-glutamic acid (Glu) segments with different γ-alkyl groups, including methyl, ethyl, and n-butyl, offer specific secondary structure, facilitating the formation of hydrogel. The L-tyrosine (Tyr) residues not only provide hydrogen-bond interactions and thus adjust the sol–gel transition temperatures, but also endow polypeptide enzyme-responsive properties. The PTyr segments could be phosphorylated, and the phosphotyrosine copolymers were amphiphilies, which could readily self-assemble into spherical aggregates and transform into sheet-like structures upon dephosphorylation by alkaline phosphatase (ALP). P(MGlu-co-Tyr/P) and P(MGlu-co-Tyr) copolymers showed good compatibility with both MC3T3-E1 and Hela cells, with cell viability above 80% at concentrations up to 1000 μg/mL. The prepared injectable polypeptide hydrogel and its enzyme-triggered self-assemblies show particular potential for biomedical applications. [ABSTRACT FROM AUTHOR]

The need for tumor postoperative treatments aimed at recurrence prevention and tissue regeneration have raised wide considerations in the context of the design and functionalization of implants. Herein, an injectable hydrogel system encapsulated with anti-tumor, anti-oxidant dual functional nanoparticles has been developed in order to prevent tumor relapse after surgery and promote wound repair. The utilization of biocompatible gelatin methacryloyl (GelMA) was geared towards localized therapeutic intervention. Zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, ZC) nanoparticles (NPs) were purposefully devised for their proficiency as reactive oxygen species (ROS) scavengers. Furthermore, injectable GelMA hydrogels loaded with ZC NPs carrying doxorubicin (ZC-DOX@GEL) were tailored as multifunctional postoperative implants, ensuring the efficacious eradication of residual tumor cells and alleviation of oxidative stress. In vitro and in vivo experiments were conducted to substantiate the efficacy in cancer cell elimination and the prevention of tumor recurrence through the synergistic chemotherapy approach employed with ZC-DOX@GEL. The acceleration of tissue regeneration and in vitro ROS scavenging attributes of ZC@GEL were corroborated using rat models of wound healing. The results underscore the potential of the multifaceted hydrogels presented herein for their promising application in tumor postoperative treatments. [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]

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]

Photoinduced metal-free ATRP has been successfully applied to fabricate thermo-responsive cellulose graft copolymer (PNIPAM-g-Cell) using 2-bromoisobuturyl bromide-modified cellulose as the macroinitiator. The polymerization of N-isopropylacrylamide (NIPAM) from cellulose was efficiently activated and deactivated with UV irradiation in the presence of an organic-based photo-redox catalyst. Both FTIR and 13C NMR analysis confirmed the structural similarity between the obtained PNIPAM-g-Cell and that synthesized via traditional ATRP methods. When the concentration of the PNIPAM-g-Cell is over 5% in water, it forms an injectable thermos-responsive hydrogel composed of micelles at 37 °C. Since organic photocatalysis is a metal-free ATRP, it overcomes the challenge of transition-metal catalysts remaining in polymer products, making this cellulose-based graft copolymer suitable for biomedical applications. In vitro release studies demonstrated that the hydrogel can continuously release DOX for up to 10 days, and its cytotoxicity indicates that it is highly biocompatible. Based on these findings, this cellulose-based injectable, thermo-responsive drug-loaded hydrogel is suitable for intelligent drug delivery systems. [ABSTRACT FROM AUTHOR]

The tissue engineering field is currently advancing towards minimally invasive procedures to reconstruct soft tissue defects. In this regard, injectable hydrogels are viewed as excellent scaffold candidates to support and promote the growth of encapsulated cells. Cross-linked gelatin methacryloyl (GelMA) gels have received substantial attention due to their extracellular matrix-mimicking properties. In particular, GelMA microgels were recently identified as interesting scaffold materials since the pores in between the microgel particles allow good cell movement and nutrient diffusion. The current work reports on a novel microgel preparation procedure in which a bulk GelMA hydrogel is ground into powder particles. These particles can be easily transformed into a microgel by swelling them in a suitable solvent. The rheological properties of the microgel are independent of the particle size and remain stable at body temperature, with only a minor reversible reduction in elastic modulus correlated to the unfolding of physical cross-links at elevated temperatures. Salts reduce the elastic modulus of the microgel network due to a deswelling of the particles, in addition to triple helix denaturation. The microgels are suited for clinical use, as proven by their excellent cytocompatibility. The latter is confirmed by the superior proliferation of encapsulated adipose tissue-derived stem cells in the microgel compared to the bulk hydrogel. Moreover, microgels made from the smallest particles are easily injected through a 20G needle, allowing a minimally invasive delivery. Hence, the current work reveals that powdered cross-linked GelMA is an excellent candidate to serve as an injectable hydrogel for adipose tissue engineering. [ABSTRACT FROM AUTHOR]

Utilizing the immune system as a strategy for disease prevention and treatment is promising, especially with dendritic cells (DCs) playing a central role in adaptive immune responses. The unique properties of DCs drive interest in developing materials for cell-based therapy and immune modulation. Injectable systems require syringe-compatible scaffolds, while hydrogels, like alginate, known for their programmability and biocompatibility, offer a versatile platform for immune medicine enhancement through easy preparation and room-temperature cross-linking. In this study, we synthesized alginate balls loaded with DCs or cytosine–phosphorothioate–guanine deoxyribonucleotide (CpG DNA) microparticles, aiming for long-term immune cell culture with potential immune stimulation effects. Encapsulated DCs exhibited proliferation within the alginate balls for up to 7 days, and CpG MPs were uniformly dispersed, which can facilitate uptake by DCs. This was supported by the result that DCs effectively phagocytosed CpG microparticles in a 2D environment. After the uptake of CpG MPs, the alginate balls with CpG-MP-uptaken DCs were synthesized successfully. The injectable properties of the alginate balls were easily modulated by adjusting the syringe needle gauges. This innovative strategy holds substantial promise for advancing medical treatments, offering effective and comfortable solutions for controlled immune modulation. [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]

Nowadays, chemotherapy is a common clinical treatment for cancer, but it still faces many limitations and challenges. Therefore, the combination of chemotherapy and other treatments often enhances the effectiveness of treatments. Herein, an injectable hydrogel of PC10ARGD/Cu2+/DOX based on Cu2+, hydrophilic doxorubicin (DOX), and genetically engineered polypeptide PC10ARGD was prepared. First, Cu2+ was attached to the histidines in the PC10ARGD polypeptide by the coordination reaction to form PC10ARGD/Cu2+ hydrogel, then the PC10ARGD/Cu2+/DOX hydrogel was prepared by encapsulating the DOX into the PC10ARGD/Cu2+ hydrogel. The results of scanning electron microscopy showed that the PC10ARGD/Cu2+/DOX hydrogel displayed loose porous morphology. In vitro, reactive oxygen species production results showed that the PC10ARGD/Cu2+/DOX hydrogel could continuously produce ·OH in the presence of H2O2. In vitro MTT results showed that the PC10ARGD/Cu2+/DOX hydrogel had a good inhibitory effect on cell activity. Flow cytometry further confirmed the antitumor effect of the PC10ARGD/Cu2+/DOX hydrogel. In vivo experiment results showed that the tumor volume of mice treated with the PC10ARGD/Cu2+/DOX hydrogel was significantly inhibited compared with control groups, which was due to the combination of chemodynamic and chemotherapy. The results of body weight and blood analysis of mice showed that the PC10ARGD/Cu2+/DOX hydrogel possessed good biocompatibility. [ABSTRACT FROM AUTHOR]

Injectable hydrogel provides an excellent substrate for bone tissue engineering (BTE) applications due to its water base, and capacity to encapsulate, manipulate, and easily reach to the adjacent tissue with minimal invasiveness. The purpose of the present study, is to develop an injectable hydrogel with a combination of chitosan, hyaluronic acid, and hydroxyapatite for enhanced bone regeneration and remodeling. Blend hydrogels have enough surface roughness and porosity that helps to attach bone cells. Hydrogel synthesis was confirmed with XRD, FTIR, EDX and TGA characterization. These hydrogels demonstrated adequate swelling and mechanical properties for its use in BTE applications. These hydrogels have the acceptable range of mechanical strength required for injectable hydrogels for bone regeneration. The synthesized hydrogel showed enough range of percolation capacity needed for the permeability of medicine, growth factors, and nutritional molecules. All these findings suggest the use of synthesized hydrogels for bone regeneration in biomedical engineering applications. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Faculty of Pharmacy of Ankara University / Ankara Üniversitesi Eczacilik Fakültesi Dergisi is the property of Ankara University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

It is often difficult to close and repair irregular wounds such as gums with traditional dressings that have a fixed shape, while injectable hydrogels that can be molded in situ offer tremendous advantages in treating complex, large wounds and can better seal or fill a variety of irregular wounds. While the majority of injectable hydrogels developed in current research have poor mechanical properties and biocompatibility and obstacles to clinical applications, this paper reports an injectable hydrogel that can be molded in situ with appropriate mechanical properties, excellent biocompatibility, and antibacterial activity. Under UV irradiation, a methacrylate-gelatin/poly-(vinyl alcohol) loaded with copper ion cross-linked tannic acid nanoparticle (GelMA/PVA-TA/Cu2+NPs) precursor solution could rapidly gel within 45 s and adhere stably to the wound tissue by topological adhesion and hydrogen bonding. Through hydrogen bonding and physical entanglement, TA/Cu2+NPs are anchored in the GelMA/PVA interpenetrating network to form the GelMA/PVA-TA/Cu2+NPs composite hydrogel. This injectable hydrogel, which can quickly achieve photocurable in situ molding, can not only achieve closure and repair of irregular wounds but also has appropriate swelling characteristics, absorbing tissue exudate and blocking bacteria, while providing a good moist environment for wounds and continuously promoting wound healing. Cytotoxicity tests and wound healing experiments have shown that GelMA/PVA-TA/Cu2+NPs injectable hydrogels have good biocompatibility and wound closure and repair ability and have promising applications in the treatment of irregularly wounded orifices. [ABSTRACT FROM AUTHOR]

The present study aimed at developing an injectable hydrogel based on acacia gum (AG) for wound healing acceleration. The hydrogels were synthetized through metal-ligand coordination mediated by Fe3+ and characterized in terms of gelation time, gel content, initial water content, swelling capacity, water retention ratio, and porosity. Moreover, FTIR, XRD and TGA analyses were performed for the hydrogels and allantoin (Alla) loaded ones. Furthermore, bioadhessiveness, and self-healing as well as antibacterial, toxicity and wound healing potentials of the hydrogels were evaluated. The hydrogels displayed fast gelation time, high swelling, porosity, and bioadhessiveness, as well as antioxidant, self-healing, antibacterial, blood clotting, and injectability properties. FTIR, XRD and TGA analyses confirmed hydrogel synthesis and drug loading. The Alla-loaded hydrogels accelerated wound healing by decreasing the inflammation and increasing the cell proliferation as well as collagen deposition. Hemocompatibility, cell cytotoxicity, and in vivo toxicity experiments were indicative of a high biocompatibility level for the hydrogels. Given the advantages of fast gelation, injectability and beneficial biological properties, the use of Alla-loaded hydrogels could be considered a new remedy for efficient wound healing. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Shanghai Jiaotong University (Medical Science) is the property of Journal of Shanghai Jiaotong University (Medical Science) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)