Injectable Hydrogel Research Articles

Drug-Loaded Mesoporous Polydopamine Nanoparticles in Chitosan Hydrogels Enable Myocardial Infarction Repair through ROS Scavenging and Inhibition of Apoptosis.

In this study, we synthesized mesoporous polydopamine nanoparticles (MPDA NPs) using an emulsion-induced interface assembly strategy and loaded epigallocatechin gallate (EGCG) into MPDA NPs via electrostatic attraction to form EGCG@MPDA NPs. In the post myocardial infarction (MI) environment, these interventions specifically aimed to eliminate reactive oxygen species (ROS) and facilitate the repair of MI. We further combined them with a thermosensitive chitosan (CS) hydrogel to construct an injectable composite hydrogel (EGCG@MPDA/CS hydrogel). Utilizing in vitro experiments, the EGCG@MPDA/CS hydrogel exhibited excellent ROS-scavenging ability of H9C2 cells under the oxidative stress environment and also could inhibit their apoptosis. The EGCG@MPDA/CS hydrogel significantly promoted left ventricular ejection fraction (LVEF) in infarcted rat models post injection for 28 days compared to the PBS group (51.25 ± 1.73% vs 29.31 ± 0.78%, P < 0.05). In comparison to the PBS group, histological analysis revealed a substantial increase in left ventricular (LV) wall thickness in the EGCG@MPDA/CS hydrogel group (from 0.58 ± 0.03 to 1.39 ± 1.11 mm, P < 0.05). This work presents a novel approach to enhance MI repair by employing the EGCG@MPDA/CS hydrogel. This hydrogel effectively reduces local oxidative stress by ROS and stimulates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.

Fabrication of injectable, adhesive, self-healing, superabsorbent hydrogels based on quaternary ammonium chitosan and oxidized pullulan

Injectable hydrogels, which are polymeric materials that are characterized by their ability to be injected in a liquid form into cavities and subsequently undergo in situ solidification, have garnered significant attention. These materials are extensively used in a range of biomedical applications. This study synthesized several injectable composite hydrogels through the mild Schiff base reaction while imposing different concentrations of quaternary ammonium chitosan and oxidized pullulan. Subsequent characterizations revealed a consistent and coherent porous structure within the hydrogels with smooth inner walls. The hydrogels were also determined to possess good adhesion, mechanical properties, self-healing ability, and injectability. Furthermore, antimicrobial tests against Escherichia coli and Staphylococcus aureus demonstrated antibacterial properties, which improved with increasing concentrations of quaternary ammonium chitosan. Co-culturing with skin fibroblasts demonstrated that the injectable hydrogels exhibited favourable biocompatibility and the capacity to boost cellular activity, thus underscoring its potential for use in biomedical applications.

Injectable, oxygen-releasing, thermosensitive hydrogel promotes vascularized bone formation with prolonged oxygen delivery and improved osteoinductivity

The failure or delay in healing of critical bone defects is primarily due to early local anoxic conditions and reduced osteogenic activity. In this research, we integrated calcium peroxide (CPO) embedded polycaprolactone (PCL) microspheres and osteoinductive nanoparticles (Hydroxyapatite/Laponite) into a thermosensitive hydrogel (Pluronic F127), thereby formulating an injectable oxygen-releasing osteogenic thermosensitive hydrogel. Notably, the oxygen-releasing microspheres (ORMs) within the composite hydrogel provide stable oxygen release for up to 21 days, ensuring the survival, migration, and bioactivity of both mesenchymal stem cells and endothelial cells under anoxic conditions. Additionally, the composite hydrogel significantly augments the osteogenic potential of bone marrow mesenchymal stem cells by providing a biomimetic microenvironment with the incorporation of nano-hydroxyapatite/laponite. Ultimately, the injectable composite hydrogel successfully stimulated bone regeneration within a cranial defect in a rat model after 8 weeks, with enhanced vascularization and bone quality. The engineered hydrogel provides a minimally invasive approach to stimulate bone regeneration with a sustained oxygen supply and osteogenic microenvironment provision, underlining its potential for treating critical bone defects.

A Multicenter, Randomized, Double-Blind, Parallel-Grouped, Positive-Controlled, Non-Inferiority Clinical Study to Evaluate the Efficacy and Safety of Injectable Calcium Hydroxylapatite Microsphere Hydrogel Fillers in the Correction of Nasolabial Fold in Chinese Subjects.

Soft tissue fillers are used to improve the appearance of nasolabial folds (NLFs). This study aimed to compare the efficacy and safety of a new calcium hydroxylapatite microsphere hydrogel filler (Aphranel) versus Restylane for correcting NLFs. In this multicenter, randomized, double-blind, parallel-grouped, positive-controlled, non-inferiority trial, 210 subjects were randomized to bilateral NLF treatment with Aphranel and Restylane on either side of the NLF. NLF was assessed before and right after injection and at the first week, first month, third, sixth, and 12 months. The primary efficacy endpoint was the WSRS improvement rate for the NLF, defined as ≥ 1 point improvement at Week 24. The secondary efficacy endpoints include the WSRS score assessed by investigators and the independent review committee (IRC) and the Global Aesthetic Improvement Scale (GAIS) evaluated by the subjects, investigators, and IRC over time. Randomization was performed using a computer-generated randomization list. To ensure the double-blind nature of the study, neither the physicians administering the injections nor the patients receiving them were aware of the specific product being used. All syringes were identical in appearance, with labels coded instead of indicating the product name. The preparation of the injection products was handled by nurses who were not involved in the treatment process, thereby maintaining the blinding of both the physicians and the patients to the treatment assignment. A total of 188 subjects (168 women and 20 men) completed the 12-month follow-up. The investigator-evaluated improvement rates using WSRS at 24 weeks were 84.04% for Aphranel and 78.72% for Restylane. The IRC-evaluated improvement rates using WSRS at 24 weeks were 72.34% for Aphranel and 70.21% for Restylane. Aphranel was shown to be statistically non-inferior to Restylane (P>0.05). Both the investigator and IRC-assessed WSRS scores over time showed that the mean scores for Aphranel were non-inferior to the mean scores for Restylane (all P>0.05). There was no difference between the Aphranel and Restylane groups according to the subjects, investigators, and IRC-assessed GAIS score at any time point (all P>0.05). Both devices' most frequently reported adverse events were injection site swelling and procedural pain. This study confirms that Aphranel is an effective and safe treatment for correcting NLFs in Chinese subjects. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Silkworm cocoon bionic design in wound dressings: A novel hydrogel with self-healing and antimicrobial properties

Hydrogels with rapid wound-healing capabilities and antimicrobial effects are gaining significant interest in related fields. Nonetheless, developing a multifunctional hydrogel wound dressing with injectable self-assembling, self-healing, antimicrobial properties, and efficient skin wound-healing capabilities remained a formidable challenge. In this experiment, we drew inspiration from silkworm cocoons' natural formation and protective mechanisms, employing a novel physical cross-linking method to create an injectable and self-healing quaternary hydrogel successfully. The hydrogel is based on a matrix of silk fibroin/silk sericin (SF/SS), with 1,2-dimyristoyl-sn-glycero-3-phosphate sodium salt (DMPG) serving as a physical cross-linking agent to form the hydrogel network structure, and the incorporation of silver nanoparticles (AgNPs) further enhances its antimicrobial capabilities. Our biomimetic hydrogel, which replicated the chemical properties of silkworm cocoons, demonstrated excellent hydrophilicity with a water contact angle that ranged from 37 to 52°. Its tensile and compressive resistance was approximately four times greater than that of a pure SF hydrogel, and its swelling performance was about three times higher than that of a pure SF hydrogel. Furthermore, the hydrogel exhibited an impressive bacterial inhibition rate of over 98 % in bacterial growth and inhibition experiments, which provided a solid foundation for accelerating wound healing. Likewise, experiments with mice and histological analyses revealed that on day 7, the expression of TNF-α and IL-1β in the wound tissues treated with the SF/SS/AgNPs hydrogel was significantly reduced by >25 % compared to the blank control group. This reduction indicates that the hydrogel could decrease the production of inflammatory cytokines, potentially aiding in the acceleration of wound healing and mitigation of inflammation-related adverse reactions. By day 14, the wounds were healed mainly, with the wound area reduced by 17 % compared to that of the blank group. This demonstrates the significant potential of this cocoon-mimetic hydrogel in accelerating wound healing and providing wound protection.

Research Progress on the Application of Injectable Hydrogel in Oral Tissue Regeneration.

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. This review aims to summarize the literature on the current status and limitations of injectable hydrogels in the field of oral tissue regeneration. We searched Pubmed and Web of Science databases to find and summarize the articles on the application of injectable hydrogels in tissue regeneration. 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.

Characterization of pentenoate-functionalized hyaluronic acid and pentenoate-functionalized gelatin hydrogels for printing and future surgical placement in regenerative medicine applications

Injectable hydrogels with in situ crosslinking may be more suitable than pre-fabricated scaffolds for surgical delivery to clinical injuries. However, low viscosity hydrogel precursors may be challenging to surgically place into an injury if the precursor leaks or is washed out. The biomaterials field for extrusion bioprinting is a fertile ground for discovering biomaterials with injectable and paste-like precursor rheology with in situ gelation capabilities, which may promote better material retention in clinical injuries. We previously developed and evaluated one formulation of a pentenoate-functionalized hyaluronic acid (PHA) / pentenoate-functionalized gelatin (PGel) hydrogel with a paste-like, printable precursor and rapid photocrosslinking in a spinal cord injury application. Further characterization of the material and cell response to PHA/PGel hydrogel formulations is needed to expand the bioprinting and other regenerative medicine opportunities for PHA/PGel hydrogels. In the current study, we utilized 2D NMR methods (i.e., 1H–1H TOCSY) to confirm and quantify a high degree of pentenoate functionalization of PGel and PHA. We characterized the stiffness, swelling, and cell viability using varying formulations of PGel or PHA/PGel hydrogels. For compression testing, a straightforward application of the Ogden model enabled evaluation of the full stress-strain range for improved moduli comparisons. We identified two formulations that best supported cell viability (i.e., 3%/10% and 4%/5% PHA/PGel). Furthermore, one of the identified formulations (4%/5% PHA/PGel) had superior printability compared to the other. With better printability and potentially better clinical surgical placement, the new PHA/PGel hydrogel formulations may be more widely applied in the bioprinting and regenerative medicine fields.

Liposomal nano-encapsulation of bFGF combined with injectable BSA hydrogel for efficient burn wound healing

Rapid and scar-free healing of burn wounds is an urgent clinical issue. Basic fibroblast growth factor (bFGF) has been proven to promote the healing of burn wounds by accelerating ECM remodeling and angiogenesis. However, exudates from burn wounds can accelerate bFGF degradation, thereby affecting its bioactivity. This study proposes an effective protection strategy for bFGF that involves encapsulating bFGF in nanoliposomes (bFGF-NLip) and then incorporating bFGF-NLip into a bovine serum albumin (BSA) hydrogel. This hybrid hydrogel system (bFGF-NLip@B) could maintain the activity of bFGF, achieve sustained release, and allow phospholipids and cholesterol to penetrate the skin, thereby enabling bFGF to function in the dermis. The experimental results showed that the hydrogel was injectable with good mechanical properties and biocompatibility. In a mouse scald wound model, owing to the sustained release of bFGF and skin permeation function of the nanoliposomes, the hydrogel promoted granulation formation, collagen deposition, vascular regeneration, and re-epithelialisation, ultimately accelerating wound healing. In addition, the hydrogel effectively inhibited scar formation. This system provides novel insights into the delivery of bFGF and scar-free healing of burn wounds.

In situ crosslinked injectable chondroitin sulfate hydrogel for preventing postoperative adhesion

Postoperative adhesion is a common clinical disease caused by surgical trauma, accompanying serious subsequent complications. Current non-surgical drug therapy and biomaterial barrier administration have limited therapeutic effects due to their inherent deficiencies. Therefore, developing a simple, effective, and feasible method to effectively prevent postoperative adhesions after surgical procedures remains a challenge. An injectable chondroitin sulfate complex hydrogel was prepared based on aldehyde-modified chondroitin sulfate (ChS-CHO) and hydrazine-modified chondroitin sulfate (ChS-ADH). The hydrogel showed enhanced strength and good self-healing ability. By using the Schiff base reaction principle that aldehyde group reacts with hydrazide to form hydrazone bond, C-A hydrogel physical barrier is formed at the wound site to reduce the occurrence of postoperative adhesion. There is no use of chemical crosslinkers in the whole reaction system to prepare C-A hydrogel, which has excellent biocompatibility and is safe and non-toxic. The results showed that C-A hydrogel showed excellent mechanical properties, good self-healing, and biocompatibility. The cecal-abdominal wall adhesion model and hepatic adhesion model of rats were constructed respectively to evaluate its preventive effect on postoperative adhesion. The results showed that C-A hydrogel had a more significant preventive effect on postoperative adhesion, and appears to be a promising candidate for postoperative adhesion.

Advances in Chitosan-Based Smart Hydrogels for Colorectal Cancer Treatment

Despite advancements in early detection and treatment in developed countries, colorectal cancer (CRC) remains the third most common malignancy and the second-leading cause of cancer-related deaths worldwide. Conventional chemotherapy, a key option for CRC treatment, has several drawbacks, including poor selectivity and the development of multiple drug resistance, which often lead to severe side effects. In recent years, the use of polysaccharides as drug delivery systems (DDSs) to enhance drug efficacy has gained significant attention. Among these polysaccharides, chitosan (CS), a linear, mucoadhesive polymer, has shown promise in cancer treatment. This review summarizes current research on the potential applications of CS-based hydrogels as DDSs for CRC treatment, with a particular focus on smart hydrogels. These smart CS-based hydrogel systems are categorized into two main types: stimuli-responsive injectable hydrogels that undergo sol-gel transitions in situ, and single-, dual-, and multi-stimuli-responsive CS-based hydrogels capable of releasing drugs in response to various triggers. The review also discusses the structural characteristics of CS, the methods for preparing CS-based hydrogels, and recent scientific advances in smart CS-based hydrogels for CRC treatment.

Zinc-induced photocrosslinked konjac glucomannan/glycyrrhizic acid hydrogel promotes skin wound healing in diabetic mice through immune regulation

Diabetic wound healing is a complex process. Owing to the lack of effective wound dressings, diabetic wound healing is often delayed. Here, injectable composite hydrogels with methacrylic anhydride (MA)-modified Konjac glucomannan and Zn2+-induced glycyrrhizic acid self-assembly were developed for skin wound healing in diabetic mice. Under induction with a photoinitiator and Zn2+, the hydrogel formed rapidly (<5 s) in vitro. The KGMMA/GA/Zn hydrogel demonstrated excellent mechanical properties (strain [40 %] >28 KPa) and physicochemical characteristics, which enabled the adaptation to various complex skin wound environments. Crucially, in vitro and in vivo experiments revealed that the hydrogel had good biocompatibility and low hemolytic properties (1.7 %) and promoted cell migration and tube formation. Hydrogels can modulate the innate properties of the immune system, regulate the polarization of macrophages in the M2 direction, and inhibit the production of ROS and inflammatory factors without the addition of cytokines or drugs in vivo and in vitro. In vivo animal experiments revealed that the hydrogel significantly accelerated the repair process of skin wounds, with a repair efficiency reaching 97.2 %. In summary, this novel hydrogel constitutes a highly effective wound healing dressing and may be a promising approach in tissue regeneration engineering.

Photo-crosslinking injectable Photothermal antibacterial hydrogel based on quaternary ammonium grafted chitosan and hyaluronic acid for infected wound healing

Antibacterial hydrogels not only provide a better environment for skin wounds to avoid infection but also accelerate wound healing. Herein, chitosan modified by a quaternary ammonium salt (CQ), and hyaluronic acid grafted with methacrylate (HM) were designed and synthesized to prepare an injectable photo-crosslinking hydrogel for wound dressing with inherent antibacterial and photothermal properties. CQ and HM exhibited excellent biocompatibility, improved water retention, and antibacterial activity, illustrating vast potential as an antibacterial material in various applications. MXene, a type of 2D nanomaterial, has been widely researched due to its photothermal properties. The CQ and HM polymer precursor could be mixed with Mxene and then crosslinked with 395 nm UV radiation under mild conditions to form a 3D network structure CQ-HM/MXene hydrogel. This hydrogel displayed an appropriate swelling ratio, elastic modulus, photothermal property and excellent biocompatibility. The injectable property of the hydrogel allowed it to easily cover the wound. In vitro and in vivo studies showed that the injectable hydrogel had low cytotoxicity and excellent antibacterial properties, which could help promote wound healing. In summary, this novel CQ-HA/MXene hydrogel has the potential for application in skin wound healing due to inherent antibacterial activity and photothermal effect.

An injectable thermosensitive hydrogel delivering M2 macrophage-derived exosomes alleviates osteoarthritis by promoting synovial lymphangiogenesis

Osteoarthritis (OA) is a prevalent chronic degenerative disease affecting millions worldwide, with current treatment measures lacking efficacy in slowing disease progression. The synovial lymphatic system (SLS) has emerged as a crucial player in OA pathogenesis, with compromised drainage function contributing to disease advancement. Lymphatic endothelial cells (LECs) within the SLS are influenced by synovial macrophages, whose precise impact on LEC function remains unclear. Exosomes released by macrophages may serve as mediators of this interaction, with potential implications for OA progression. Here, we propose that polarized macrophages modulate LEC activity via exosome release in synovial tissue, with M2 macrophage-derived exosomes (M2Exo) promoting LEC proliferation, migration, and lymphangiogenesis, potentially offering a therapeutic avenue for OA. Moreover, we developed an injectable thermosensitive hydrogel with the characteristic of sustained release of M2Exo for alleviating OA. The hydrogel was prepared by dynamically linking hyaluronic acid (HA) and Pluronic F-127 and loading M2Exo, termed as M2Exo loaded HP hydrogel. The in vitro and in vivo experiments showed that M2Exo loaded HP hydrogel exhibits a controlled release profile of exosomes, thereby efficaciously fostering synovial lymphangiogenesis and enhancing synovial lymphatic drainage functionality under OA conditions, thus alleviating OA progression, and providing promising insights into OA therapeutic strategies. Statement of significanceOsteoarthritis (OA) is a widespread degenerative disease with limited effective treatments to halt its progression. This research highlights the critical role of the synovial lymphatic system (SLS) in OA, focusing on how macrophage-derived exosomes influence lymphatic endothelial cell (LEC) function. We propose that M2 macrophage-derived exosomes (M2Exo) enhance LEC activity, promoting lymphangiogenesis, and offering a therapeutic approach for OA. Furthermore, we developed an injectable thermosensitive hydrogel (M2Exo loaded HP hydrogel) for sustained M2Exo release. Our in vitro and in vivo experiments demonstrate that this hydrogel supports synovial lymphangiogenesis and improves lymphatic drainage, effectively alleviating OA progression. This study presents significant advancements in OA therapy, offering new insights into its management.

Fortifying the foundation: assessing the role of uterine ligament integrity in uterine prolapse and beyond.

Pelvic floor stability is influenced by various biomechanical, anatomical, and physiological factors. Understanding these dynamics is crucial for improving the treatment of pelvic organ prolapse (POP) and related conditions. To analyze the key factors affecting pelvic floor integrity and explore both non-surgical and surgical interventions to enhance stability and treatment outcomes. This review draws from biomechanical research to assess the role of the uterosacral ligament in pelvic support, while also examining the potential of both traditional and emerging therapeutic approaches, including non-surgical interventions like vitamin C supplementation. - The uterosacral ligament demonstrates superior strength and stiffness, making it essential for structural support of pelvic organs. - Non-surgical interventions, such as vitamin C supplementation, show potential in improving ligament integrity and preventing pelvic floor disorders. - Emerging surgical techniques, including tendon-based procedures and injectable fibrous hydrogel composites, offer promising improvements in outcomes for patients with pelvic organ prolapse. - Additional factors such as muscle strength and neural deficiencies contribute to the complexity of pelvic floor biomechanics, indicating the need for multifaceted treatment approaches. This analysis provides a comprehensive framework for understanding and managing pelvic floor stability by integrating biomechanical, physiological, and anatomical insights. The findings highlight the potential for personalized treatment strategies to improve patient outcomes in pelvic floor disorders.

Near-Infrared Carbon Dots With Antibacterial and Osteogenic Activities for Sonodynamic Therapy of Infected Bone Defects.

Repairing infected bone defects is hindered by the presence of stubborn bacterial infections and inadequate osteogenic activity. The incorporation of harmful antibiotics not only fosters the emergence of multidrug-resistant bacteria, but also diminishes the osteogenic properties of scaffold materials. In addition, it is essential to continuously monitor the degradation kinetics of scaffold materials at bone defect sites, yet the majority of bone repair materials lack imaging capability. To address these issues, this study reports for the first time the development of a single nanomaterial with triple functionality: efficient sonodynamic antibacterial activity, accelerated bone defect repair capability, and NIR imaging ability for visualized therapy of infected bone defects. Through rationally regulating the surface functional groups, the obtained multifunctional NIR carbon dots (NIR-CD) exhibit p-n junction-enhanced sonodynamic activity, narrow bandgap-facilitated NIR imaging capability, and negative charge-augmented osteogenic activity. The validation of NIR-CDs antibacterial and osteogenic activities in vivo is conducted by constructing 3D injectable hydrogels encapsulated by NIR-CDs (NIR-CD/GelMA). The implantation of multifunctional NIR-CD/GelMA hydrogel scaffolds in a model of MRSA-infected craniotomy defects results in almost complete restoration of the infected bone defects after 60 days. These findings will provide traceable, renewable, repairable and antibacterial candidate biomaterials for bone tissue engineering.

Conductive, injectable, and self-healing collagen-hyaluronic acid hydrogels loaded with bacterial cellulose and gold nanoparticles for heart tissue engineering

The increasing demand for advanced biomaterials in nerve tissue engineering presents numerous challenges due to the complexity of nerve tissues and the need for materials that can accurately replicate their intricate structure and function. In response, this study introduces a novel injectable hydrogel that is thermosensitive, self-healing, and conductive, offering promising potential for heart and nerve tissue engineering applications. The hydrogel is based on collagen and hyaluronic acid functionalized with 3-aminopropyl-triethoxysilane (APTES)-grafted oxidized bacterial cellulose and gold nanoparticles (~50 nm). Rheological analysis reveals a substantial enhancement in the elastic modulus of the collagen-hyaluronic acid matrix with the incorporation of bacterial cellulose/gold nanoparticles, improving by an order of magnitude at 1 % strain. This improvement comes with a slight decrease in gelation temperature, from 36 °C to 32 °C. Besides thermo-sensitivity, the nanocomposite hydrogel exhibits a remarkable self-sealing response (about 80 % effectiveness) due to reversible physical crosslinking. Electrical spatial resistance measurements on human embryonic stem cell-derived cardiomyocytes-loaded hydrogels yield a value of ~0.1 S/m, which is suitable for electrical stimulation. In vitro extracellular field potential measurements also affirm the hydrogel's potential as an injectable scaffold for heart tissue engineering, i.e., the electrically stimulated human stem cells exhibit 47 beats per minute with a cell discharge (depletion) of 5.47 μv. A rapid gel formation in the physiological temperature (about 2 min) and high H9C2 cytotoxicity (viability of >90 % after 72 h incubation) is attainable. The developed collagen-based nanocomposite hydrogel offers an injectable, thermosensitive, and self-healing biomaterial platform for nerve or myocardium regeneration.

Laponite modified methacryloyl gelatin hydrogel with controlled release of vascular endothelial growth factor a for bone regeneration

Reconstruction of bone defects has long been a major clinical challenge. Limited by the various shortcomings of conventional treatment like autologous bone grafting and inorganic substitutes, the development of novel bone repairing strategies is on top priority. Injectable biomimetic hydrogels that deliver stem cells and growth factors in a minimally invasive manner can effectively promote bone regeneration and thus represent a promising alternative. Therefore, in this study, we designed and constructed an injectable nanocomposite hydrogel co-loaded with Laponite (Lap) and vascular endothelial growth factor (VEGF) through a simplified and convenient scheme of physical co-mixing (G@Lap/VEGF). The introduced Lap not only optimized the injectability of GelMA by the electrostatic force between the nanoparticles, but also significantly delayed the release of VEGF-A. In addition, Lap promoted high expression of osteogenic biomarkers in mesenchymal stem cells (MSCs) and enhanced the matrix mineralization. Besides, VEGF-A exerted chemotactic effects recruiting endothelial progenitor cells (EPCs) and inducing neovascularization. Histological and micro-CT results demonstrated that the critical-sized calvarial bone defect lesions in the SD rats after treated with G@Lap/VEGF exhibited significant in vivo bone repairing. In conclusion, the injectable G@Lap/VEGF nanocomposite hydrogel constructed in our study is highly promising for clinical transformation and applications, providing a convenient and simplified scheme for clinical bone repairing, and contributing to the further development of the injectable biomimetic hydrogels.

Injectable Salecan/hyaluronic acid-based hydrogels with antibacterial, rapid self-healing, pH-responsive and controllable drug release capability for infected wound repair

Designing materials for wound dressings with superior therapeutic benefits, self-healing and injectable characteristics is important in clinical practice. Herein, a new self-healing injectable hydrogel was prepared via thermal treatment and dynamic Schiff base reaction by mixing oxidized hyaluronic acid (OHA) and hydrazided Salecan (Sal-ADH). The versatility of the wound dressing was confirmed by studying the inherent rheological properties, high swelling rate, sustained-release behavior of the drug, pH/hyaluronidase-dependent biodegradation, in vitro antimicrobial as well as in vivo wound healing performance. The presence of the antimicrobial drug polyhexamethylene biguanide (PHMB) conferred good antimicrobial properties to the Sal-ADH/OHA/PHMB (SOP) hydrogel, which could effectively prevent wound infection (the width of the inhibition circle of SOP-0.20 hydrogel was 4.97 mm, 5.93 mm for Staphylococcus aureus and Escherichia coli, respectively). The findings suggested that SOP hydrogel exhibited remarkable self-healing and injectability properties, as well as excellent hemostasis and biocompatibility. In vivo experiments indicated that the application of SOP hydrogels would obviously accelerate wound healing and attenuate the inflammatory response while increasing collagen deposition and angiogenesis. Altogether, antibacterial SOP hydrogels with moderate mechanical properties, pH-responsive release, excellent injectability, exceptional self-healing ability and anti-inflammatory effects could expand potential applications of injectable hydrogels in the biomedical field.

Phenylboronic Acid-Functionalized Injectable Polypeptide Hydrogels with Responsive Drug Release

Phenylboronic Acid-Functionalized Injectable Polypeptide Hydrogels with Responsive Drug Release

Preparation of injectable self-healing hydrogels using carboxymethyl chitosan and oxidized dextran with incorporating quercetin-loaded PF127 micelles for wound healing

Rapid achievement of the irregularly shaped post-wound closure is closely related to the effectiveness of clinical hydrogel-based wound dressings to inhibit microbial invasion and promote wound healing. Herein, an injectable and self-healing hydrogel with rapid gelation was engineered based on carboxymethyl chitosan (CMCS) and oxidized dextran (Odex). The hydrophobic drug, quercetin, with antioxidant and antibacterial effects, was loaded in the PF127 micelles with an encapsulation efficiency of 59.06 %, and then quercetin-loaded PF127 micelles were ingeniously incorporated into the hydrogels. The prepared composite hydrogels not only showed a stable and sustained release behavior of quercetin, but also possessed excellent antioxidant activities and antibacterial properties against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. Moreover, the composite hydrogels with microstructure (150–250 μm) also exhibited self-healing and injectable properties. In addition, the survival rates of NIH 3T3 cells when cultured with hydrogel extract were all over 80 %, illustrating the excellent biocompatibility of hydrogels. Therefore, our prepared multifunctional composite hydrogels showed a broad prospect as wound dressings for treating acute skin injuries.