Injectable Composite Hydrogel Research Articles

Injectable composite hydrogels embedded with gallium-based liquid metal particles for solid breast cancer treatment via chemo-photothermal combination

Photothermal therapy (PTT) holds great promise as a cancer treatment modality by generating localized heat at the tumor site. Among various photothermal agents, gallium-based liquid metal (LM) has been widely used as a new photothermal-inducible metallic compound due to its structural transformability. To overcome limitations of random aggregation and dissipation of administrated LM particles into a human body, we developed LM-containing injectable composite hydrogel platforms capable of achieving spatiotemporal PTT and chemotherapy. Eutectic gallium–indium LM particles were first stabilized with 1,2-Distearoyl-sn‑glycero-3-phosphoethanolamine (DSPE) lipids. They were then incorporated into an interpenetrating hydrogel network composed of thiolated gelatin conjugated with 6-mercaptopurine (MP) chemodrug and poly(ethylene glycol)-diacrylate. The resulted composite hydrogel exhibited sufficient capability to induce MDA-MB-231 breast cancer cell death through a multi-step mechanism: (1) hyperthermic cancer cell death due to temperature elevation by near-infrared laser irradiation via LM particles, (2) leakage of glutathione (GSH) and cleavage of disulfide bonds due to destruction of cancer cells. As a consequence, additional chemotherapy was facilitated by GSH, leading to accelerated release of MP within the tumor microenvironment. The effectiveness of our composite hydrogel system was evaluated both in vitro and in vivo, demonstrating significant tumor suppression and killing. These results demonstrate the potential of this injectable composite hydrogel for spatiotemporal cancer treatment. In conclusion, integration of PTT and chemotherapy within our hydrogel platform offers enhanced therapeutic efficacy, suggesting promising prospects for future clinical applications. Statement of significanceOur research pioneers a breakthrough in cancer treatments by developing an injectable hydrogel platform incorporating liquid metal (LM) particle-mediated photothermal therapy and 6-mercaptopurine (MP)-based chemotherapy. The combination of gallium-based LM and MP achieves synergistic anticancer effects, and our injectable composite hydrogel acts as a localized reservoir for specific delivery of both therapeutic agents. This platform induces a multi-step anticancer mechanism, combining NIR-mediated hyperthermic tumor death and drug release triggered by released glutathione from damaged cancer populations. The synergistic efficacy validated in vitro and in vivo studies highlights significant tumor suppression. This injectable composite hydrogel with synergistic therapeutic efficacy holds immense promise for biomaterial-mediated spatiotemporal treatment of solid tumors, offering a potent targeted therapy for triple negative breast cancers.

Injectable nanoparticle-crosslinked xyloglucan/ε-poly-l-lysine composite hydrogel with hemostatic, antimicrobial, and angiogenic properties for infected wound healing

Skin wounds are susceptible to infection, leading to severe inflammatory reactions that can progress to chronic wounds, ultimately causing significant physical and mental distress to the patient. In this study, we propose an injectable composite hydrogel achieved through one-pot gelation of oxidized xyloglucan (OXG), cationic polyamide ε-poly-l-lysine (EPL), and surface amino-rich silicon nanoparticles (SiNPs). OXG exhibits commendable anti-inflammatory properties and provides crosslinking sites. SiNPs serve as mechanically reinforced crosslinkers, facilitating the construction of a dynamic Schiff base network. SiNPs significantly reduced the gelation time to 3 s and tripled the storage modulus of the hydrogels. Additionally, the combination of EPL and SiNPs demonstrated synergistic antimicrobial activity against both S. aureus and E. coli. Notably, the hydrogel effectively halted liver bleeding within 30 s. The hydrogel demonstrated outstanding shear-thinning and self-healing properties, crucial considerations for the design of injectable hydrogels. Furthermore, its efficacy was evaluated as a wound dressing in a mouse model with S. aureus infection. The results indicated that, compared to commercial products, the hydrogel exhibited a shorter wound healing time, decreased inflammation, thinner epithelium, increased hair follicles, enhanced neovascularization, and more substantial collagen deposition. These findings strongly suggest the promising potential of the proposed hydrogel as an effective wound dressing for the treatment of infected wounds.

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

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

Injectable mesoporous bioactive glass/sodium alginate hydrogel loaded with melatonin for intervertebral disc regeneration.

Intervertebral disc degeneration (IDD) is a major contributing factor to both lower back and neck pain. As IDD progresses, the intervertebral disc (IVD) loses its ability to maintain its disc height when subjected to axial loading. This failure in the weight-bearing capacity of the IVD is a characteristic feature of degeneration. Natural polymer-based hydrogel, derived from biological polymers, possesses biocompatibility and is able to mimic the structure of extracellular matrix, enabling them to support cellular behavior. However, their mechanical performance is relatively poor, thus limiting their application in IVD regeneration. In this study, we developed an injectable composite hydrogel, namely, Mel-MBG/SA, which is similar to natural weight-bearing IVD. Mesoporous bioactive glasses not only enhance hydrogels, but also act as carriers for melatonin (Mel) to suppress inflammation during IDD. The Mel-MBG/SA hydrogel further provides a mixed system with sustained Mel release to alleviate IL-1β-induced oxidative stress and relieve inflammation associated with IDD pathology. Furthermore, our study shows that this delivery system can effectively suppress inflammation in the rat tail model, which is expected to further promote IVD regeneration. This approach presents a novel strategy for promoting tissue regeneration by effectively modulating the inflammatory environment while harnessing the mechanical properties of the material.

Kartogenin-loaded hydrogel promotes intervertebral disc repair via protecting MSCs against reactive oxygen species microenvironment by Nrf2/TXNIP/NLRP3 axis.

Intervertebral disc (IVD) degeneration (IDD) and the consequent low back pain present a major medical challenge. Stem cell-based tissue engineering is promising for the treatment of IDD. However, stem cell-based treatment is severely impaired by the increased generation of reactive oxygen species (ROS) in degenerative disc, which can lead to a high level of cell dysfunction and even death. In this study, a kartogenin (KGN)@PLGA-GelMA/PRP composite hydrogel was designed and used as a carrier of ADSCs-based therapies in disc repair. Injectable composite hydrogel act as a carrier for controlled release of KGN and deliver ADSCs to the degenerative disc. The released KGN can stimulate the differentiation of ADSCs into a nucleus pulposus (NP) -like phenotype and boost antioxidant capacity of ADSCs via activating Nrf2/TXNIP/NLRP3 axis. Furthermore, the composite hydrogel combined with ADSCs attenuated the in vivo degeneration of rat IVDs, maintained IVD tissue integrity and accelerated the synthesis of NP-like extracellular matrix. Therefore, the KGN@PLGA-GelMA/PRP composite hydrogel is a promising strategy for stem cell-based therapies of IDD.

Injectable decellularized extracellular matrix hydrogel loaded with exosomes encapsulating curcumin for prevention of cardiac fibrosis after myocardial infarction

Excessive cardiac fibrosis impairs cardiac repair after myocardial infarction (MI). In this work, an injectable composite hydrogel integrating natural biomaterials, exosomes, and bioactive molecules is developed to prevent or alleviate cardiac fibrosis. Curcumin, a natural molecule with antifibrotic activity, is encapsulated in the exosomes that are isolated from bone marrow-derived mesenchymal stem cells to enhance its water solubility and bioavailability. These composite exosomes are efficiently internalised by fibroblasts and effectively inhibit their transition to myofibroblasts in vitro. Decellularized porcine cardiac extracellular matrix (dECM) hydrogel is used as the carrier for delivering these composite exosomes to the infarcted myocardium, not only improving the retention of exosomes but also providing mechanical support and structural protection. Injection of this hydrogel into the infarcted heart of a mouse MI model leads to a decrease in collagen deposition, alleviation of fibrosis, a reduction in infarct size, and an improvement in cardiac function. The reported composite hydrogel comprising natural materials and biomolecules exhibits good biocompatibility and bioactivity. Altogether, this study demonstrates that the dECM hydrogel is a suitable platform for the local delivery of antifibrotic biomolecule-encapsulating exosomes to prevent myocardial fibrosis after MI and have great potential for the treatment of MI in clinical settings.

Extracellular Matrix/Glycopeptide Hybrid Hydrogel as an Immunomodulatory Niche for Endogenous Cardiac Repair after Myocardial Infarction.

The treatment of myocardial infarction (MI) remains a substantial challenge due to excessive inflammation, massive cell death, and restricted regenerative potential, leading to maladaptive healing process and eventually heart failure. Current strategies of regulating inflammation or improving cardiac tissue regeneration have limited success. Herein, a hybrid hydrogel coassembled by acellular cardiac extracellular matrix (ECM) and immunomodulatory glycopeptide is developed for endogenous tissue regeneration after MI. The hydrogel constructs a niche recapitulating the architecture of native ECM for attracting host cell homing, controlling macrophage differentiation via glycopeptide unit, and promoting endotheliocyte proliferation by enhancing the macrophage-endotheliocyte crosstalk, which coordinate the innate healing mechanism for cardiac tissue regeneration. In a rodent MI model, the hybrid hydrogel successfully orchestrates a proreparative response indicated by enhanced M2 macrophage polarization, increased angiogenesis, and improved cardiomyocyte survival, which alleviates infarct size, improves wall thicknesses, and enhances cardiac contractility. Furthermore, the safety and effectiveness of the hydrogel are demonstrated in a porcine MI model, wherein proteomics verifies the regulation of immune response, proangiogenesis, and accelerated healing process. Collectively, the injectable composite hydrogel serving as an immunomodulatory niche for promoting cell homing and proliferation, inflammation modulation, tissue remodeling, and function restoration provides an effective strategy for endogenous cardiac repair.

Injectable nano-composite hydrogels based on hyaluronic acid-chitosan derivatives for simultaneous photothermal-chemo therapy of cancer with anti-inflammatory capacity

Nowadays, the photothermal therapy (PTT) has received widespread attention and research by rapidly killing tumors with local high temperature. However, due to the irregular edges of tumor and the blurred boundary between normal and necrotic tissues, the desirable treatment cannot be achieved by the single PTT, and excessive heat will cause serious inflammation in local tissues. Herein, an injectable composite hydrogel is prepared by the oxidized hyaluronic acid (OHA) and hydroxypropyl chitosan (HPCS) via the imine bonds, which is employed as the delivery substrate for functional substances. In the gel medium, the mesoporous polydopamine (MPDA) nanoparticles are incorporated as the high efficiency photothermal agent and a reservoir of DOX, which can achieve the good photothermal conversion performance and pulsed drug release. Besides, the addition of the curcumin-cyclodextrin host-guest inclusion complex (CUR@NH2-CD) in the composite hydrogel could reduce the inflammation caused by PTT. The composite hydrogel shows favorable the Hepa1–6 tumor inhibition in vivo by virtue of the comprehensive effect of the admired photothermal efficacy of MPDA, chemotherapy of DOX and anti-inflammatory of CUR. It can be predicted that the composite hydrogel has a broad prospect in the field of comprehensive therapy for tumor.

A poly (glycerol-sebacate-acrylate) nanosphere enhanced injectable hydrogel for wound treatment.

Wound repair remains a huge clinical challenge, which can cause bleeding, infection, and patient death. In our current research, a bioactive, injectable, multifunctional composite hydrogel doped with nanospheres was prepared with antibacterial and angiogenesis-promoting functions for the treatment of wounds. Amino groups in ε-polylysine (ε-EPL) undergo dynamic Schiff base reaction cross-linking with oxidized hyaluronic acid (OHA), and F127 exhibits unique temperature sensitivity to form an injectable thermosensitive hydrogel (FHE10), which can form a hydrogel to cover the wound at body temperature. Nanospheres (PNs) prepared using poly (glyceryl-sebacate-acrylate) (PGSA) were loaded into hydrogels (FHE10) for promoting wound repair. The prepared FHE10 exhibited rapid gelation, good injectable abilities, and showed resistance to the flourish of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vitro investigations showed that FHE10 had good hemocompatibility and cytocompatibility. FHE10@PNs exhibited good proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) and human foreskin fibroblasts (HFF-1). Furthermore, FHE10@PNs significantly promoted reepithelialization and collagen deposition as well as micro-vascularization compared with the use of FHE10 or PNs alone, thereby accelerating the repair of wounds. In general, this study demonstrated that the multifunctional injectable composite hydrogel showed great potential in wound treatment.

An Injectable Hydrogel Scaffold Loaded with Dual-Drug/Sustained-Release PLGA Microspheres for the Regulation of Macrophage Polarization in the Treatment of Intervertebral Disc Degeneration.

Due to the unique physical characteristics of intervertebral disc degeneration (IVDD) and the pathological microenvironment that it creates, including inflammation and oxidative stress, effective self-repair is impossible. During the process of intervertebral disc degeneration, there is an increase in the infiltration of M1 macrophages and the secretion of proinflammatory cytokines. Here, we designed a novel injectable composite hydrogel scaffold: an oligo [poly (ethylene glycol) fumarate]/sodium methacrylate (OPF/SMA) hydrogel scaffold loaded with dual-drug/sustained-release PLGA microspheres containing IL-4 (IL-4-PLGA) and kartogenin (KGN-PLGA). This scaffold exhibited good mechanical properties and low immunogenicity while also promoting the sustained release of drugs. By virtue of the PLGA microspheres loaded with IL-4 (IL-4-PLGA), the composite hydrogel scaffold induced macrophages to transition from the M1 phenotype into the M2 phenotype during the early induced phase and simultaneously exhibited a continuous anti-inflammatory effect through the PLGA microspheres loaded with kartogenin (KGN-PLGA). Furthermore, we investigated the mechanisms underlying the immunomodulatory and anti-inflammatory effects of the composite hydrogel scaffold. We found that the scaffold promoted cell proliferation and improved cell viability in vitro. While ensuring mechanical strength, this composite hydrogel scaffold regulated the local inflammatory microenvironment and continuously repaired tissue in the nucleus pulposus via the sequential release of drugs in vivo. When degenerative intervertebral discs in a rat model were injected with the scaffold, there was an increase in the proportion of M2 macrophages in the inflammatory environment and higher expression levels of type II collagen and aggrecan; this was accompanied by reduced levels of MMP13 expression, thus exhibiting long-term anti-inflammatory effects. Our research provides a new strategy for promoting intervertebral disc tissue regeneration and a range of other inflammatory diseases.

Graphene Oxide/Chitosan Injectable Composite Hydrogel for Controlled Release of Doxorubicin: An Approach for Enhanced Intratumoral Delivery

Intratumoral (IT) injection of chemotherapeutics into needle-accessible solid tumors can directly localize the anticancer drug in the tumor site, thus increasing its local bioavailability and reducing its undesirable effects compared to systemic administration. In this study, graphene oxide (GO)-based chitosan/β-glycerophosphate (CS/GP) thermosensitive injectable composite hydrogels (CH) were prepared and optimized for the localized controlled delivery of doxorubicin (DOX). A quality-by-design (QbD) approach was used to study the individual and combined effects of several formulation variables to produce optimal DOX-loaded GO/CS/GP CH with predetermined characteristics, including gelation time, injectability, porosity, and swelling capacity. The surface morphology of the optimal formulation (DOX/opt CH), chemical interaction between its ingredients and in vitro release of DOX in comparison to GO-free CS/GP CH were investigated. Cell viability and cellular uptake after treatment with DOX/opt CH were studied on MCF 7, MDB-MB-231 and FaDu cell lines. The statistical analysis of the measured responses revealed significant effects of the concentration of GO, the concentration of CS, and the CS:GP ratio on the physicochemical characteristics of the prepared GO/CS/GP CH. The optimization process showed that DOX-loaded GO/CS/GP CH prepared using 0.1% GO and 1.7% CS at a CS: GO ratio of 3:1 (v/v) had the highest desirability value. DOX/opt CH showed a porous microstructure and chemical compatibility between its ingredients. The incorporation of GO resulted in an increase in the ability of the CH matrices to control DOX release in vitro. Finally, cellular characterization showed a time-dependent increase in cytotoxicity and cellular uptake of DOX after treatment with DOX/opt CH. The proposed DOX/opt CH might be considered a promising injectable platform to control the release and increase the local bioavailability of chemotherapeutics in the treatment of solid tumors.

Injectable composite hydrogel based on carbon particles for photothermal therapy of bone tumor and bone regeneration

• Injectable composite hydrogel based on carbon particles is developed. • Carbon particles can serve as photothermal agents to ablate osteosarcoma tissues. • Injectable composite hydrogel facilitates the conformal therapy of bone defects. • Composite hydrogel promotes the new bone formation with a high BV/TV ratio of 76.2%. Surgical resection, as the most efficient treatment for bone tumor, still faces a dilemma between the complete removal of tumor tissue and the maximum reservation of healthy bone tissue. In response to this, an injectable composite hydrogel with chitosan/hyaluronic acid/ β -sodium glycerophosphate as the matrix and carbon particles as the photothermal agent is developed. Owing to the temperature sensitivity, the composite hydrogel can be injected into the irregular bone defect and exhibit the sol-gel phase transition upon body temperature, facilitating the conformal therapy. The composite hydrogel can ablate the human osteosarcoma on Balb/c nude mice model with the tumor inhibition rate of 98.4% after near-infrared laser irradiation (808 nm). The assessment of bone regeneration on calvarial-defect model of Sprague-Dawley rats reveals that the composite hydrogel can promote new bone formation with the bone volume/total volume ratio of 76.2% after 8 weeks, in sharp contrast to the control group of 23.9%.

Genipin-crosslinked fibrin seeded with oxidized alginate microbeads as a novel composite biomaterial strategy for intervertebral disc cell therapy

Discectomy procedures alleviate disability caused by intervertebral disc (IVD) herniation, but do not repair herniation-induced annulus fibrosus (AF) defects. Cell therapy shows promise for IVD repair, yet cell delivery biomaterials capable of sealing AF defects and restoring biomechanical function have poor biological performance. To balance the biomechanical and biological demands of IVD cell delivery biomaterials, we engineered an injectable composite biomaterial using cell-laden, degradable oxidized alginate (OxAlg) microbeads (MBs) to deliver AF cells within high-modulus genipin-crosslinked fibrin (FibGen) hydrogels (FibGen + MB composites). Conceptually, the high-modulus FibGen would immediately stabilize injured IVDs, while OxAlg MBs would protect and release cells required for long-term healing. We first showed that AF cells microencapsulated in OxAlg MBs maintained high viability and, upon release, displayed phenotypic AF cell morphology and gene expression. Next, we created cell-laden FibGen + MB composites and demonstrated that OxAlg MBs functionalized with RGD peptides (MB-RGD) minimized AF cell apoptosis and retained phenotypic gene expression. Further, we showed that cell-laden FibGen + MB composites are biomechanically stable and promote extracellular matrix (ECM) synthesis in long-term in vitro culture. Lastly, we evaluated cell-laden FibGen + MB-RGD composites in a long-term bovine caudal IVD organ culture bioreactor and found that composites had low herniation risk, provided superior biomechanical and biological repair to discectomy controls, and retained anabolic cells within the IVD injury space. This novel injectable composite hydrogel strategy shows promise as an IVD cell delivery sealant with potentially broad applications for its capacity to balance biomechanical and biological performance.

An injectable and conductive TEMPOL/polypyrrole integrated peptide co-assembly hydrogel promotes functional maturation of cardiomyocytes for myocardial infarction repair

A cell-implantation strategy offers a promising paradigm for cardiac repair after myocardial infarction (MI). However, the hostile reactive oxygen species (ROS) microenvironment in infarcted zone hinders the survival and maturation of implanted cells and affects the ultimate therapeutic outcome. Besides, the generation of fibrosis scarring deprives the myocardium of electrical communications and induces cardiac dysfunction, eventually resulting in heart failure. Herein, an injectable ROS-scavenging/conductive composite hydrogel (R&C-Gel) was constructed via specific binding between conductive polypyrrole (PPy) and multi-component co-assembly peptides. Integrating antioxidant TEMPOL into the peptide endows it with strong ROS-eliminating ability, and the nanoengineering of polypyrrole (PPy) by wet milling facilitates PPy uniformly binding to the target T59 peptide in nanofibers . The thixotropy of co-assembly hydrogels confirmed by rheology and the macroporous structure of the R&C-Gel surface observed by SEM together suggest that the R&C-Gel could be an ideal vehicle for cell engraftment. The antioxidant ability and electroconductivity of the R&C-Gel were verified. In vitro experiments demonstrated that the R&C-Gel could efficiently remove ROS in cardiomyocytes and reduce apoptosis under oxygen-glucose deprivation (OGD) conditions. The rhythmic intracellular Ca 2+ puffs and expression of Cx-43 protein further proved the R&C-Gel could enhance the electrical and contractile performance of cardiomyocytes. Echocardiography and histological analysis convincingly revealed that the R&C-Gel-combined cardiomyocytes significantly promoted cardiac repair and rebuilt cardiac function, such as reducing apoptosis, accelerating gap junction formation , increasing ejection fraction , and decreasing the fibrosis area. This study provides new insight into the design and construction of multifunctional conductive hydrogels for cardiac tissue engineering . • An injectable composite hydrogel (R&C-Gel) is prepared via specific binding between conductive PPy and multi-component peptides. • Integrating the TEMPOL endows the R&C-Gel with strong ROS-eliminating ability to reduce the apoptosis of CMs under hypoxia. • Nanoengineering of vapor-polymerized PPy membrane to conductive NanoClusters facilitates PPy uniformly binding to nanofibers of R&C-gel. • R&C-Gel promotes rhythmic intracellular Ca 2+ puffs and the expression of Cx-43 protein in the maturation of CMs. • Injection of CMs@R&C-Gel is capable of restoring cardiac function post-MI.

Sustained and Microenvironment-Accelerated Release of Minocycline from Alginate Injectable Hydrogel for Bacteria-Infected Wound Healing.

During wound healing, bacterial infection is one of the main limiting factors for the desired efficiency. Wound dressing-mediated antibiotics therapies could overcome this problem to a great extent due to sustained drug release and controllable dose. Here, we designed a kind of alginate injectable hydrogel loaded with minocycline (SA@MC) as a dressing for staphylococcus aureus-infected wound healing. SA@MC hydrogel possessed good injectability and can be injected by syringes. MC participated in the gel formation, causing the microstructure change based on the morphology characterization. The element mapping and FT-IR spectra further confirmed the successful loading of MC in SA hydrogel. Interestingly, MC was released more efficiently in a weakly alkaline condition (pH 7–8) than in a weakly acidic condition (pH 4–6) from SA@MC injectable hydrogel, which means that there is an accelerated release to respond to the weakly alkaline wound microenvironment. Meanwhile, SA@MC injectable hydrogel had high biocompatibility and excellent antibacterial activity due to the sustained release of MC. Further, in vivo experiment results demonstrated that SA@MC injectable hydrogel promoted staphylococcus aureus-infected wound healing efficiently. In summary, the injectable composite hydrogel can serve as an ideal dressing to prevent bacterial infection and promote wound healing.

Development of Injectable Hydroxyapatite/2-(dimethylamino)Ethyl Methacrylate/Polyvinylpyrrolidone Aqua-Hydrogel System to Repair of the Shoulder Joint Head for Hemiarthroplasty.

This study aimed to develop osteogenic structure assembly for modular bone treatment presentations, effect of 2-(dimethylamino)ethyl methacrylate and polyvinyl pyrrolidone combination as cell adhesive molecule with hydroxyapatite-based composite as osteoconductive constituent was inspected on bone fracture repair. The prepared injectable composite hydrogel showed significantly improved mechanical stability. The ternary composite gel was characterized for functional group modifications and chemical interactions using Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). Moreover, X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analyses were performed to observe surface appearances of the hydrogel. The hydroxyapatite/2-(dimethylamino)ethyl methacrylate/poly-N-vinyl-2-pyrrolidone hydrogel played key role in supporting osteoblastic cell spread due to their bioactivity and strength abilities. The present findings revealed the significance of hydroxyapatite concentration on proliferation and osteogenic purpose of the cells. The developed performances of hydrogel have been improved cell proliferation and functions to repair bone fracture.

Comparative analysis of different drug delivery methods of injectable hydrogel nanomaterials of insulin biomaterials via multiple daily injections and continuous subcutaneous insulin infusion in the treatment of type 1 diabetes mellitus in children

The aim of this study was to investigate the difference between multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII) in blood glucose control during the treatment of type 1 diabetes mellitus (T1DM) in children. under the nano-hydrogel delivery carrier. In order to improve the efficiency and therapeutic effect of the experiment, this paper adopts injectable nanomaterial-polymer composite hydrogel as drug delivery system to cooperate with insulin injection to improve the effective utilization of drugs. Eighty children diagnosed with T1DM by the department of Endocrinology, Genetics, and Metabolism of INNER MONGOLIA BAOGANG Hospital from October 2018 to December 2019 were selected as research subjects for this study. The children were randomly divided into MDI group (treated with MDI) and CSII group (treated with CSII), with 40 children in each group. The basic data of the children were compared, and changes in hemoglobin A1c (HbA1c) at admission and 1, 2, and 3 months after treatment were detected. During the detection, the blood glucose level, therapeutic time of blood glucose normalization, and daily insulin dosage were recorded. The HbA1c and fasting blood glucose (FBG) were followed up three months after discharge, and incidences of hypoglycemia in the two groups were observed. The results showed that the mean value of HbA1c in the MDI group was higher than that in the CSII group (P < 0.05). Each patient was assessed for the number of times their blood sugar was allowed to dip below normal levels; patients with less hypoglycemia had a higher rate of blood sugar control. The control rates of blood glucose in the MDI and CSII groups were 19.21% and 23.50%, respectively. The CSII group showed significantly higher blood glucose rates than the MDI group (P < 0.05). The therapeutic time of blood glucose normalization in the MDI group was significantly longer than that in the CSII group (P < 0.05). There was no significant difference in the average daily insulin dosage between the MDI and CSII groups (P > 0.05), which indicated that CSII therapy had significant advantages in reducing blood glucose in children with T1DM.

Multifunctional Injectable Hydrogel Loaded with Cerium-Containing Bioactive Glass Nanoparticles for Diabetic Wound Healing.

Diabetic foot wound healing is a major clinical problem due to impaired angiogenesis and bacterial infection. Therefore, an effective regenerative dressing is desiderated with the function of promoting revascularization and anti-bacteria. Herein, a multifunctional injectable composite hydrogel was prepared by incorporation of the cerium-containing bioactive glass (Ce-BG) into Gelatin methacryloyl (GelMA) hydrogel. The Ce-BG was synthesized by combining sol-gel method with template method, which maintained spherical shape, chemical structure and phase constitution of bioactive glass (BG). The Ce-BG/GelMA hydrogels had good cytocompatibility, promoted endothelial cells migration and tube formation by releasing Si ion. In vitro antibacterial tests showed that 5 mol % CeO2-containing bioactive glass/GelMA (5/G) composite hydrogel exhibited excellent antibacterial properties. In vivo study demonstrated that the 5/G hydrogel could significantly improve wound healing in diabetic rats by accelerating the formation of granulation tissue, collagen deposition and angiogenesis. All in all, these results indicate that the 5/G hydrogel could enhance diabetic wound healing. Therefore, the development of multifunctional materials with antibacterial and angiogenic functions is of great significance to promote the repair of diabetic wound healing.

Fabrication and characterization of an injectable reinforced composite scaffold for cartilage tissue engineering: an in vitro study

There are limitations in current medications of articular cartilage injuries. Although injectable bioactive hydrogels are promising options, they have decreased biomechanical performance. Researchers should consider many factors when providing solutions to overcome these challenges. In this study, we created an injectable composite hydrogel from chitosan and human acellular cartilage extracellular matrix (ECM) particles. In order to enhance its mechanical properties, we reinforced this hydrogel with microporous microspheres composed of the same materials as the structural building blocks of the scaffold. Articular cartilage from human donors was decellularized by a combination of physical, chemical, and enzymatic methods. The decellularization efficiency was assessed by histological analysis and assessment of DNA content. We characterized the composite constructs in terms of storage modulus, gelation time, biocompatibility, and differentiation potential. The results showed that mechanical behavior increased with an increase in microsphere content. The sample that contained 10% microsphere had an enhanced storage modulus of up to 90 kPa. Biocompatibility and preliminary differentiation investigations revealed that this composite hydrogel might have potential benefits for cartilage tissue engineering.

Injectable composite hydrogel promotes osteogenesis and angiogenesis in spinal fusion by optimizing the bone marrow mesenchymal stem cell microenvironment and exosomes secretion

With the development of tissue engineering, it is no longer a challenge to repair and reconstruct bone defects using bone substitutes. However, in spinal fusion surgery, high rates of fusion failure are difficult to avoid. In our study, we designed a new composite hydrogel and found that it has good osteogenesis and angiogenesis effects. We extracted exosomes produced by rBMSCs (rat bone marrow mesenchymal stem cells) cocultured with the hydrogel to investigate their effects on osteogenesis and angiogenesis.The results showed that the PG/TCP (PEGMC with β-TCP) promoted rapid osteogenesis, facilitated spinal fusion at a high rate and quality and had an indirect effect on angiogenesis. We found that PG/TCP affected the rBMSC microenvironment, thus changing the function of exosomes; in a further study, we found that PG/TCP-MSC-Exos played a significant role in osteogenesis, which was coupled to angiogenesis. Thus, PG/TCP showed excellent potential in bone regeneration, especially the PG/0.2TCP.