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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]

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]

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]

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]

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]

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]

Biopolymer-based injectable hydrogels with antibacterial activity have attracted considerable attention for biomedical applications. Herein, we report on an effective preparation of injectable double network hydrogel by adding zinc acetate (ZnOAc2) into an aqueous mixture of methylcellulose (MC) and chitosan (CS) at room temperature and then heating to T = 37 °C, in which the complexation of the CS with Zn2+ ion took place immediately and the MC underwent thermogelation at elevated temperature. The influence of both the CS and different salts (i.e., Zn(NO3)2, ZnCl2 and ZnOAc2) on the thermogelation of MC solution was investigated via inverted vial test and UV–Vis measurement. The results indicated that the thermogelation temperature of 1.0% w/v MC was about 60.8 °C, which decreased to 35.7 °C when mixed with 1.0% w/v CS and 0.3 mol/L sodium acetate. The mechanical properties of various hydrogels were evaluated via rheological analysis at different temperatures. A detailed study about the antibacterial activities of the resulting MC/CS hydrogels was carried out against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, confirming that the MC/CS double network hydrogel indeed exhibited excellent antibacterial activity when compared with pristine thermo-responsive MC hydrogel. At last, the injectability of the MC/CS hydrogel was also evaluated on a home-built double-syringe injection device. [ABSTRACT FROM AUTHOR]

This study highlights the development of smart stimuli-responsive carrier for controlled drug release system. Novel cytocompatible and injectable carriers were synthesized using chitosan and poly(vinyl alcohol) with different amounts of 3-aminopropyl(diethoxy)methylsilane (3-APDEMS). The characterizations of the prepared samples were accomplished via FTIR, SEM, TGA, mechanical properties, swelling, biodegradation, antimicrobial activity, antioxidant activity, anti-inflammatory activity, cytotoxicity and drug release profile. FTIR analysis was performed to approve the siloxane linkages among the integrated constituents. SEM images demonstrated the morphology, while TGA showed the highest thermal stability (593 °C offset temperature) for hydrogel with 150 μL APDEMS concentration. The antimicrobial response of hydrogels toward Bacillus cereus and E.coli was noticeable. The antioxidant activity and anti-inflammatory activity were performed to check the behavior of the MCP series against the free radical generating substance and inflammation response, respectively. All stimuli-responsive crosslinked carriers appeared cytocompatible for plated 3T3 fibroblast cells as inspected by continuous increase in the viability of cells from 24 to 48 h and 72 h post initial seeding in all samples. The swelling behavior in buffer solution (at different pH) confirmed these carriers as pH-responsive. These carriers at optimum amount of 3-APDEMS showed 99.5% drug release in phosphate buffer saline solution at 7.4 pH. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to improve the performance and mode of administration of a glass-reinforced hydroxyapatite synthetic bone substitute, Bonelike by Biosckin® (BL®), by association with a dextrin-based hydrogel, DEXGEL, to achieve an injectable and moldable device named DEXGEL Bone. Methods: Twelve participants requiring pre-molar tooth extraction and implant placement were enrolled in this study. BL® granules (250–500 µm) were administered to 6 randomized participants whereas the other 6 received DEXGEL Bone. After 6 months, a bone biopsy of the grafted area was collected for histological and histomorphometric evaluation, prior to implant placement. The performance of DEXGEL Bone and BL® treatments on alveolar preservation were further analyzed by computed tomography and Hounsfield density analysis. Primary implant stability was analyzed by implant stability coefficient technique. Results: The healing of defects was free of any local or systemic complications. Both treatments showed good osseointegration with no signs of adverse reaction. DEXGEL Bone exhibited increased granule resorption (p = 0.029) accompanied by a tendency for more new bone ingrowth (although not statistically significant) compared to the BL® group. The addition of DEXGEL to BL® granules did not compromise bone volume or density, being even beneficial for implant primary stability (p = 0.017). Conclusions: The hydrogel-reinforced biomaterial exhibited an easier handling, a better defect filling, and benefits in implant stability. Clinical relevance: This study validates DEXGEL Bone safety and performance as an injectable carrier of granular bone substitutes for alveolar ridge preservation. Trial registration: European Databank on Medical Devices (EUDAMED) No. CIV-PT-18–01-02,705; Registo Nacional de Estudos Clínicos, RNEC, No. 30122. [ABSTRACT FROM AUTHOR]

Overproduction of reactive oxygen species is one of the important reasons of non-healing wounds, such as diabetic wounds. Melatonin is well known as an antioxidant, while the poor solubility limits its use in many areas. In this study, the solubility of melatonin was improved by introducing γ-cyclodextrin to form the composite named MT-γ-CD through ultrasonic process. During this process, the molar ratio of melatonin and γ-cyclodextrin was 2:1, the temperature was set at 30 ℃, and the ultrasonic time was 40 min. The MT-γ-CD showed good antioxidant property in vitro with high free radical scavenging efficiency over 90%. Besides, an injectable self-healing hydrogel was prepared to load with MT-γ-CD to form the wound dressing, here, sodium carboxymethylated cellulose was oxidized to introduce aldehyde groups that could form Schiff base with amino groups in gelatin. This dressing with good biocompatibility could be injected into irregular wounds, suppress the level of reactive oxygen species, and accelerate wound healing of diabetic rats in vivo. Therefore, it has great potential to provide a new treatment strategy for diabetic wounds. [ABSTRACT FROM AUTHOR]

Regarding the crucial role of both bacteria and oxidants in the progression of periodontal diseases, developing multifunctional drug carriers with simultaneous antibacterial, antioxidant, and anti-inflammatory characteristics is essential to combat periodontal disease efficiently. Herein, a multifunctional injectable hydrogel containing natural compounds, including berberine (BBR) and carnosine (CAR) in a xanthan (XG) matrix (CAR/BBR/XG), was prepared. The Physicochemical, rheological, and microstructural properties of four formulations of the immobilized CAR and/or BBR in XG were evaluated. FTIR, UV–Vis, and SEM–EDS analyses were employed to assess the successful immobilization of CAR and BBR. CAR/BBR/XG continuously released ~ 80% of BBR after 168 h. According to the antimicrobial study, BBR played a crucial role in combating the understudied oral microbes (A. actinomycetemcomitans, S. mutans, C. albicans, and S. aureus). In addition, both MTT and trypan blue dye exclusion assays confirmed the cytocompatibility of the target hydrogel against human gingival fibroblast (HGF) cells and also approved the significant cytoprotective role of CAR controlling the toxicity of BBR. Finally, CAR/BBR/XG showed a high scavenging effect (> 95%) confirmed by DPPH and FRAP analyses and a low expression of interleukins (IL-6 and IL-8), approving synergistically potent antioxidant and anti-inflammatory effects of the hydrogel, respectively. In short, a facile synthesized method for preparing a new formulation containing the cytocompatible level of BBR with acceptable antibacterial as well as significant antioxidant and anti-inflammatory effects was proposed, which holds a strong promise as an injectable multifunctional hydrogel for periodontal treatment.Graphical abstract: Regarding the crucial role of both bacteria and oxidants in the progression of periodontal diseases, developing multifunctional drug carriers with simultaneous antibacterial, antioxidant, and anti-inflammatory characteristics is essential to combat periodontal disease efficiently. Herein, a multifunctional injectable hydrogel containing natural compounds, including berberine (BBR) and carnosine (CAR) in a xanthan (XG) matrix (CAR/BBR/XG), was prepared. The Physicochemical, rheological, and microstructural properties of four formulations of the immobilized CAR and/or BBR in XG were evaluated. FTIR, UV–Vis, and SEM–EDS analyses were employed to assess the successful immobilization of CAR and BBR. CAR/BBR/XG continuously released ~ 80% of BBR after 168 h. According to the antimicrobial study, BBR played a crucial role in combating the understudied oral microbes (A. actinomycetemcomitans, S. mutans, C. albicans, and S. aureus). In addition, both MTT and trypan blue dye exclusion assays confirmed the cytocompatibility of the target hydrogel against human gingival fibroblast (HGF) cells and also approved the significant cytoprotective role of CAR controlling the toxicity of BBR. Finally, CAR/BBR/XG showed a high scavenging effect (> 95%) confirmed by DPPH and FRAP analyses and a low expression of interleukins (IL-6 and IL-8), approving synergistically potent antioxidant and anti-inflammatory effects of the hydrogel, respectively. In short, a facile synthesized method for preparing a new formulation containing the cytocompatible level of BBR with acceptable antibacterial as well as significant antioxidant and anti-inflammatory effects was proposed, which holds a strong promise as an injectable multifunctional hydrogel for periodontal treatment. [ABSTRACT FROM AUTHOR]

Hypoxia is a huge barrier for the development of photodynamic therapy (PDT). Chemodynamic therapy (CDT) could provide a possible solution to this dilemma. In this work, a controlled Schiff-base reaction was conducted between amido groups on the surface of carbon dots (CDs) and aldehyde groups on aldehyde-modified cellulose nanocrystals (mCNCs) as well as aldehyde-mCNCs decorated with Fe3O4 nanoparticles. In this process, the mCNCs not only prevent the agglomeration of Fe3O4 but also form hydrogels with CDs. The CDs act as both photothermal agent and photosensitizer. The hypoxia could be effectively relieved through the Fenton reaction due to the addition of Fe3O4, and the ·OH produced in the reaction further induces CDT and enhances tumor therapy efficiency. The therapy performance was further verified through in vitro cell experiments and in vivo animal experiments. This convenient method provides inspirations for the design and preparation of advanced biomaterials with multiple functions for cancer therapy. [ABSTRACT FROM AUTHOR]

In-situ forming hydrogels have gained noticeable attention to encapsulate osteogenic agents and regenerate irregular-shape bone defects. In this study, a novel thermosensitive hydrogel based on blended methylcellulose (MC) with Persian gum (PG) was fabricated and enriched with taxifolin (TAX) loaded halloysite nanotubes (HNTs) to enhance mechanical and biological characteristics of the hydrogel in bone tissue engineering. The injectability, mechanical and rheological tests were performed for different hydrogel formulations containing 0.25–1.5 w/v% PG and 1–7 w/v% HNTs. Also, to evaluate the impact of PG and HNTs on hydrogel behavior, the degradation rate and swelling degree of hydrogels were assessed. The optimized MC/PG/HNTs hydrogel containing 1% PG and 3% HNTs (MC/PG-1/HNTs 3%) was easily injectable and gelled rapidly at physiological temperature, while it had the highest mechanical strength due to the existence of PG and HNTs. In vitro release study of TAX from this system also revealed more sustained release compared to HNTs-TAX nanoparticles. Furthermore, the interaction of cells with hydrogel and osteo-conductivity was studied using osteoblast-like cells (MG-63). Results showed higher cell adhesion, proliferation, and gene expression for MC/PG-1/HNTs-TAX hydrogel compared to MC/PG-1 and MC/PG-1/HNTs 3% possibly due to the synergic effect of HNTs and TAX. In addition, Alizarin Red S staining and alkaline phosphatase measurements indicated that the existence of HNTs-TAX promoted osteogenic differentiation. Eventually, animal studies on the femoral defects indicated improved remedy when using the MC/PG-1/HNTs-TAX hydrogel carrying MG-63 cells. [ABSTRACT FROM AUTHOR]

Injectable hydrogels as an important class of biomaterials have gained much attention in tissue engineering. However, their crosslinking degree is difficult to be controlled after being injected into body. As we all know, the crosslinking degree strongly influences the physicochemical properties of hydrogels. Therefore, developing an injectable hydrogel with tunable crosslinking degree in vivo is important for tissue engineering. Herein, we present a dual crosslinking strategy to prepare injectable hydrogels with step-by-step tunable crosslinking degree using Schiff base reaction and photopolymerization. The developed hyaluronic acid/poly(γ-glutamic acid) (HA/γ-PGA) hydrogels exhibit step-by-step tunable swelling behavior, enzymatic degradation behavior and mechanical properties. Mechanical performance tests show that the storage moduli of HA/γ-PGA hydrogels are all less than 2000 Pa and the compressive moduli are in kilopascal, which have a good match with soft tissue. In addition, NIH 3T3 cells encapsulated in HA/γ-PGA hydrogel exhibit a high cell viability, indicating a good cytocompatibility of HA/γ-PGA hydrogel. Therefore, the developed HA/γ-PGA hydrogel as an injectable biomaterial has a good potential in soft tissue engineering. [ABSTRACT FROM AUTHOR]

Poloxamer hydrogels are thermoresponsive hydrogels that become fluid when cooled and gel-like when heated. Adding poloxamer 188 to a poloxamer 407 solution increases the overall gelation temperature, thereby allowing adjustments to the window of operating temperatures. The rheological properties of the poloxamer hydrogel, including gelation temperature and gelation time, were investigated, and the biocompatibility, drug release, and antibacterial properties of a gentamicin-loaded hydrogel were determined. An injectable hydrogel was successfully formulated using 20 wt% of poloxamer 407 and 3 wt% of poloxamer 188. This system became fluid at room temperature (25 °C) in the presence of deionized water; at human body temperature (37 °C), it changed to a gel-like state. The gelation time was approximately 95 seconds. The poloxamer hydrogels showed no cytotoxicity to L929 cells after seven days of culturing. A poloxamer hydrogel loaded with gentamicin sulfate, an antibiotic, was studied for its antibacterial properties against E. coli, B. cereus, S. aureus, and MRSA using gentamicin solution as the control. The results showed that the gentamicin-loaded poloxamer hydrogel inhibited bacteria from the first hour of testing. Moreover, the zone of inhibition of the gentamicin-loaded poloxamer hydrogel was larger than that of the gentamicin solution for a similar concentration of gentamicin sulfate. It can be a potent drug carrier for infected cavity wounds. [ABSTRACT FROM AUTHOR]

Injectable hydrogels have been widely studied for the use as scaffolds or as carriers of therapeutic agents including proteins, cells, drugs, and bioactive molecules in the disease treatment and the regeneration and repair of tissues. Collagen-based hydrogels and pectin that mimic the extracellular matrix are generally applied to maintain the balance between physical and biofunctional features. In this study, preparation and characterization of novel hydrogels based on oxidized-konjac glucomannan (OKG), collagen, and oxidized-pectin (OP) have been successfully developed. Fabricated hydrogels were evaluated for their morphological, degradation, thermal stability, and mechanical properties. The physicochemical properties of OKG/collagen hydrogels without pectin (HG) or with pectin (HGP) and oxidized-pectin (HGOP) were studied. The results presented that with the addition of the OP content, the hydrogels degradation behavior and mechanical properties were improved. In addition, HGOP hydrogels enhanced the cell proliferation without any cytotoxic effect on mouse embryonic fibroblast (NIH-3T3) cells. These achieved results suggested that the developed hydrogel could be a suitable candidate to be applied for tissue engineering scaffolds. [ABSTRACT FROM AUTHOR]

Stem cell transplantation is a promising therapy for wound healing, but the low retention and survival of transplanted stem cells limit their application. Injectable hydrogels exert beneficial effects in skin tissue engineering. In this study, an injectable hydrogel composed of sodium alginate (SA) and collagen type I (Col) was synthesized as a tissue scaffold to improve the efficacy of stem cells in a full-thickness excision wound model. Our results showed that SA/Col hydrogel was injectable, biodegradable, and exhibited low immunogenicity, which could promote the retention and survival of hUC-MSCs in vivo. SA/Col loaded with hUC-MSCs showed reduced wound size (p < 0.05). Histological and immunofluorescence results confirmed that SA/Col loaded with hUC-MSCs significantly promoted the formation of granulation, enhanced collagen deposition and angiogenesis, increased VEGF and TGF-β1 expression (p < 0.05), and mitigated inflammation evidenced by lower production of TNF-α and IL-1β and higher release of IL-4 and IL-10 (p < 0.05). Furthermore, SA/Col loaded with hUC-MSCs significantly lowered the expression of NLRP3 inflammasome-related proteins (p < 0.05). Taken together, our results suggest that SA/Col loaded with hUC-MSCs promotes skin wound healing via partly inhibiting NLRP3 pathway, which has potential to the treatment of skin wounds. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) exhibits a complicated and ever-accelerated pathological change involving excessive reactive oxygen species (ROS) and the up-regulation of pro-inflammatory cytokines in the initial stage, and a permanently inadequate blood supply. Herein, an injectable hydrogel fabricated by nanoparticles (NPs) knotted thiolated hyaluronic acid (HA-SH) was reported to reverse the hostile microenvironment and rebuild the heart functions after MI Inspired by the composite shell-core structure of Ferrero chocolate sphere, a mimetic nanocarrier was designed to consist of the hydrophobic dimethyloxalylglycine (DMOG) NPs core and a thick polydopamine (PDA) shell formed by the self-polymerization of dopamine embedded with water-soluble drug epigallocatechin-3-gallate (EGCG) through π-π interactions. The resulted "Ferrero-like" NPs exhibited a "three-in-one" capacity, namely loading two distinct drugs, elimination of ROS, and serving a crosslinker to knot HA-SH. "Ferrero-like" NPs and HA-SH could rapidly form a hydrogel that exhibited a stable mechanical property, high capability to capture ROS, and programmed release of EGCG and DMOG. Four weeks after deploying the "Ferrero-like" NPs knotted hydrogels into rat infarcted hearts, the ejection fraction (EF) increased by 23.7%, and the infarct size decreased by 21.1%, and the fibrotic area reduced by 24.4%. The outcomes of immunofluorescence staining and reverse transcription-polymerase chain reaction (RT-PCR) demonstrated a down-regulation of inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interferon-γ (IFN-γ)), up-regulation of vascular related growth factors (hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGFA), von Willebrand factor (vWF), angiopoietin-1 (Ang-1)) and cardiac-related mRNAs (gap junction protein (C×43), Cadherin 2). All in all, in this report, a very simple approach to intertemporally address the intricate and ongoing pathological changes after MI by injecting "Ferrero-like" NPs knotted hydrogels is developed to reverse hostile microenvironment, with an ability to scavenge ROS, down-regulate pro-inflammation factors in the first stage, and promote angio-genesis in a long term, thereby contributing to a significant improvement of heart functions. [ABSTRACT FROM AUTHOR]

We assessed an injectable gelatin hydrogel containing epidermal growth factor (Gtn-EGF) as a therapy for intracerebral hemorrhage (ICH). ICH was induced in rats via collagenase injection into the striatum. Two weeks later, Gtn-EGF was injected into the cavitary lesion. The hydrogel filled ICH cavities without deforming brain tissue. Immunostaining demonstrated that neural precursor cells could migrate into the matrix, and some of these differentiated into neurons along with the appearance of astrocytes, oligodendrocytes, and endothelial cells. Sensorimotor tests suggested that Gtn-EGF improved neurological recovery. This study provides proof-of-principle that injectable biomaterials may be a translationally relevant approach for treating ICH. [ABSTRACT FROM AUTHOR]

Injectable hydrogel is one of the most important biomaterials for tissue engineering and drug delivery. However, it is still a challenge to obtain an injectable hydrogel with conductive property on account of the poor water solubility of conductive polymers Here, a conductive hydrogel with controllable biodegradability was constructed for minimally delivering adipose mesenchymal stem cells (ADSCs). Firstly, a disulfide containing and hyperbranched polymer structure poly(β-amino ester) (PBAE) with multi-acrylate end groups was synthesized by poly(ethylene glycol) diacrylate(PEGDA) and cystamine, and then tetraaniline (TA) was grafted on the PBAE chain to obtain a conductive PBAE-TA polymer. PBAE-TA shows a good water solubility, which can be crosslinked by thiol-modified hyaluronic acid (HA-SH) due to the click reaction between acrylate and thiol to in situ form a hydrogel within 1 min. The hydrogel illustrates a good electrical conductivity of 9.6×10−3 S/cm and a controllable biodegradable behavior in dithiothreotol (DTT) solution. PBAE-TA HA-SH hydrogel was subcutaneously injected for delivering ADSCs. The gene expression of Cx43 and TGF-β1 were up-regulated by PBAE-TA/HA-SH hydrogel, suggesting an enhancement in the electrical coupling and an anti-inflammatory property. This injectable, biodegradable, and conductive hydrogel can effectively deliver stem cells, which might be used in skin, muscle, and myocardium regeneration. [ABSTRACT FROM AUTHOR]

The work focuses on the development of an injectable chitosan-fibrin (CF) based nanocomposite hydrogel for angiogenic response. The hydrogel base is made of chitosan gel, 3% (wt/wt) of which is composed of fibrin. The injectable nanocomposite gel was prepared by incorporating nanocurcumin (nC) 100-150 nm in size, with a zeta potential of + 33.5 ± 3 mV into the CF hydrogel. The gel was characterized by scanning electron microscopy and rheometry for the morphological and visco-elastic properties. Furthermore, cytocompatibility and angiogenic response of the CF hydrogel was analyzed with human umbilical cord vein endothelial cells. In vitro tube formation and nitric oxide release assay revealed the improved angiogenic behavior of the nanocomposite hydrogel when compared to the control. Further, angiogenesis was confirmed by ex vivo aortic sprouting assay. These studies suggest that the developed injectable chitosan-fibrin/nanocurcumin (CF/nC) hydrogel can be used for angiogenic stimulation. [ABSTRACT FROM AUTHOR]

Novel degradable thermosensitive injectable hydrogels with two-phase composite structure and improved mechanical strength were prepared by adding sodium alginate or dextran to the aqueous solution of a hydrolytically degradable ABA triblock copolymer with poly(ethylene glycol) middle block and poly(N-isopropylacrylamide) containing in-chain ester groups as side blocks. The two-phase structure, demonstrated by SEM measurements, resulted as a consequence of the triblock copolymer-biopolymer incompatibility. The biopolymer addition decreased the gelation temperature ( T ) and strongly improved the viscoelastic properties of the resulted hydrogel, whose behavior at 37 °C turned from liquid-like to a gel-like one. The composite hydrogels displayed low gelation time and high stability (i.e., no sign of syneresis after 42 days) at 37 °C. They partially degraded in PBS at 37 °C as a consequence of the hydrolysis of the in-chain ester groups of the thermosensitive blocks, leading to a progressive increase of T and decrease of gel strength. The ability of the composite hydrogels to control the release rate of drugs was tested in PBS at 37 °C by employing 5-flurouracil (5FU) and chlorambucil (CLB) as model drugs with different hydrophilicity. 5FU displayed a pretty fast release rate, unlike CLB whose release rate was much slower, no effect of the biopolymer nature being noticed. During the drug release experiments, the hydrogels showed a moderate mechanical stability, although higher than in the absence of the biopolymer, and also progressively dissolved within 12-17 days because of the hydrogel erosion phenomenon, probably accelerated by the partial degradation of the triblock copolymer. [ABSTRACT FROM AUTHOR]

The aim of this study was to obtain the fillers in the lumen of hollow nerve conduits (NCs) to improve the microenvironment of nerve regeneration. A pH-induced injectable chitosan (CS)-hyaluronic acid (HA) hydrogel for nerve growth factor (NGF) sustained release was developed. Its properties were characterized by gelation time, FT-IR, SEM, in vitro swelling and degradation. Furthermore, the in vitro NGF release profiles and cell biocompatibility were also investigated. The experimental results show that the CS-HA aqueous solution can undergo a rapid gelation 3 minutes after its environmental pH is changed to 7.4. The CS-HA hydrogel has interconnected channels with a controllable pore diameter and with a porosity of about 80%. It has a favorable swelling behavior and can be degraded by about 70% within 8 weeks in vitro and is suitable for NGF release. The CS-HA/NGF hydrogel exhibits a lower cytotoxicity and is in favor of the adhesion and proliferation of the BMMSCs cells. It is indicated that the CS-HA/NGF will be a promising candidate for neural tissue engineering. [ABSTRACT FROM AUTHOR]

pH and redox dual stimuli-responsive injectable hydrogels were prepared by cross-linking oxidized carboxymethyl cellulose (oxi-CMC) with 3,3'-dithiobis (propionohydrazide) (DTP) via Schiff base reaction under physiological condition. The hydrogels showed good performance such as tunable gelling time, appropriate rheology properties, high swelling ratio and low degradation rate. In vitro release studies confirmed that bovine serum albumin (BSA) as a model drug exhibited a sustainable release at pH 7.4 and an accelerated release under a lower pH 5.0 and/or reducing environments. The results signified that oxi-CMC/DTP hydrogels could be an attractive candidate for drug delivery system, tissue engineering or cell scaffold materials. [ABSTRACT FROM AUTHOR]

Gelatin hydrogels have recently attracted much attention for tissue regeneration because of their biocompatibility. In this study, we introduce poly-ethylene glycol (PEG)-grafted gelatin containing tyramine moieties which have been utilized for in situ enzyme-mediated hydrogel preparation. The hydrogel can be used to load nanoparticles of biphasic calcium phosphate, a mixture of hydroxyapatite and β-tricalcium phosphate, and forming injectable bio-composites. Proton nuclear magnetic resonance (H NMR) spectra indicated that tyramine-functionalized polyethylene glycol-nitrophenyl carbonate ester was conjugated to the gelatin. The hydrogel composite was rapidly formed in situ (within a few seconds) in the presence of horseradish peroxidase and hydrogen peroxide. In vitro experiments with bio-mineralization on the hydrogel composite surfaces was well-observed after 2 weeks soaking in simulated body fluid solution. The obtained results indicated that the hydrogel composite could be a potential injectable material for bone regeneration. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the effect of locally delivered pancreatic islet with liposomal clodronate (Clodrosome®) as an immunoprotection agent for the treatment of type 1 diabetes. Method: The bio-distribution of liposomal clodronate in matrigel was checked by imaging analyzer. To verify the therapeutic efficacy of locally delivered islet with liposomal clodronate using injectable hydrogel, four groups of islet transplanted mice ( n = 6 in each group) were prepared: 1) the islet group, 2) the islet-Clodrosome group, 3) the islet-Matrigel group, and 4) the islet-Matrigel-Clodrosome group. Immune cell migration and activation, and pro-inflammatory cytokine secretion was evaluated by immunohistochemistry staining and ELISA assay. Results: Cy5.5 labeled liposomes remained in the matrigel for over 7 days. The median survival time of transplanted islets (Islet-Matrigel-Clodrosome group) was significantly increased (>60 days), compared to other groups. Locally delivered liposomal clodronate in matrigel effectively inhibited the activation of macrophages, immune cell migration and activation, and pro-inflammatory cytokine secretion from macrophages. Conclusions: Locally co-delivered pancreatic islets and liposomal clodronate using injectable hydrogel effectively cured type 1 diabetes. Especially, the inhibition of macrophage attack in the early stage after local delivery of islets was very important for the successful long-term survival of delivered islets. [ABSTRACT FROM AUTHOR]

In this study, chondrocytes were encapsulated into an injectable, in situ forming type II collagen/hyaluronic acid (HA) hydrogel cross-linked with poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4SPEG) and supplemented with the transforming growth factor β (TGFβ). The chondrocyte-hydrogel constructs were cultured in vitro for 7 days and studied for cell viability and proliferation, morphology, glycosaminoglycan production, and gene expression. Type II collagen/HA/4SPEG formed a strong and stable hydrogel, and the chondrocytes remained viable during the encapsulation process and for the 7-day culture period. In addition, the encapsulated cells showed spherical morphology characteristic for chondrocytic phenotype. The cells were able to produce glycosaminoglycans into their extracellular matrix, and the gene expression of type II collagen and aggrecan, genes specific for differentiated chondrocytes, increased over time. The results indicate that the studied composite hydrogel with incorporated chondrogenic growth factor TGFβ is able to maintain chondrocyte viability and characteristics, and thus, it can be regarded as potential injectable cell delivery vehicle for cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

In this study, an hydrogel was synthesized from the monomer N-isopropylacrylamide (NIPA), generating the poly( N-isopropylacrylamide) (PNIPA) and other formulations were synthesized in the presence of 1, 2, and 3% hyaluronic acid (HA) for obtain an interpenetrating polymer network. For all the obtained hydrogels, the thermo-sensitive response was studied since the lower critical solution temperature (LCST) and was analyzed by differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and oscillatory rheology at constant frequency as a function of temperature. The LCST transition temperature ( Tt onset) was found between 34.4 and 35.5 °C. By scanning electron microscopy (SEM) PNIPA-HA formulations showed a porous morphology. The applicability of the hydrogels as injectable and non-toxic materials was verified, respectively, by rheology results and by cytotoxicity studies through an in vitro test of cell hemolysis on blood agar. [ABSTRACT FROM AUTHOR]

novel pH- and temperature-responsive multiblock copolymer consisting of poly(ethylene glycol) (PEG) and poly(amino-ester urethane) (PAEU) is reported. First, a biodegradable monomer, bis-1,4-(hydroxyethyl)piperazine mono-lactate (HEP mono-lactate), was synthesized by the ring-opening polymerization of D,L-lactide (LA) using HEP and Sn(Oct) as an initiator and catalyst, respectively. The multiblock copolymers were synthesized further from PEG, HEP, HEP mono-lactate, and 1,6-diisocyanatohexamethylene (HDI) in the presence of dibutyltin dilaurate as a catalyst. The resulting copolymers were characterized by nuclear magnetic resonance spectroscopy (NMR), Fourier transform infrared spectroscopy (FTIR), and gel permeation chromatography (GPC). At pH 6.8 or higher, the copolymer aqueous solutions showed gel-to-sol transitions with increasing temperature, and the gel window covered the physiological conditions. After a subcutaneous injection of the multiblock copolymer solution into SD rats, a soft gel was formed in a short time. The degradability of the copolymer was adjusted by varying the LA content in the PAEU block. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Injectable hydrogels are quite promising materials due to their potential to minimize invasive implantation and this provides versatile fitness irrespective of the damaged regions and facilitates the incorporation of bioactive agents or cells. In situ gel formation through stereocomplex formation is a promising candidate for injectable hydrogels. In this paper, a new series of enantiomeric, four-arm, PEG-PLA block copolymers and their stereocomplexed hydrogels were prepared by bulk ring-opening polymerization of D-lactide and L-lactide, respectively, with stannous octoate as a catalyst. The prepared polymers were characterized byH nuclear magnetic resonance (NMR) spectroscopy, Fourier-transform infrared (FT IR) spectroscopy, gel permeation chromatography (GPC) and thermal gravitational analysis (TGA), confirming the tailored structure and chain lengths. The swelling and degradation behavior of the hydrogels formed from a selected copolymer series were observed in different concentrations. The degradation rate decreased with increasing polymer content in the solution. The rheological behavior indicated that the prepared hydrogel underwent in situ gelation and had favorable mechanical strength. In addition, its feasibility as an injectable scaffold was evaluated using a media dependence test for cell culture. A Tris solution was more favorable for in situ gel formation than PBS and DMEM solutions were. These results demonstrated the in situ formation of hydrogel through the construction of a stereocomplex with enantiomeric, 4-arm, PEG-PLA copolymers. Overall, enantiomeric, 4-arm, PEG-PLA copolymers are a new species of stereocomplexed hydrogels that are suitable for further research into injectable hydrogels. [ABSTRACT FROM AUTHOR]

A novel injectable composite hydrogel based on chitosan and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) reinforced with nanohydroxyapatite particles was synthesized. The chemical structure and morphology of the composite hydrogel were characterized. The composite hydrogel porosity, swelling, mechanical properties, viscoelasticity and in vitro biodegradation were also examined. Compared with the non-reinforced hydrogel, the composite hydrogel showed increased compressive strength, elastic modulus, viscous modulus, stiffness and had shear-thinning behaviour proving the injectability of the system. Swelling and biodegradation studies revealed that the composite scaffold possesses proper hydrophilicity and biodegradability. These properties make this composite hydrogel a promising injectable scaffold for bone regeneration. [ABSTRACT FROM AUTHOR]