Injectable Nanocomposite Hydrogels Research Articles

Coordinating Macrophage Targeting and Antioxidation by Injectable Nanocomposite Hydrogel for Enhanced Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA), an immune-mediated inflammatory disease, is characterized by a large number of infiltrated immune cells and abnormally elevated reactive oxygen species (ROS) in the joint. Various proinflammatory factors secreted by macrophages and the elevated ROS by inflammatory cells are deeply intertwined and together contribute to joint damage. Targeted and sustained anti-inflammation and antioxidation strategies are needed for RA treatment. To alleviate the oxidative stress and target the source of inflammatory cytokines, we developed a thermosensitive injectable hydrogel, Dex-DSLip/Cro@Gel, to coordinate the targeted anti-inflammatory and antioxidation effects. Within the injectable gel, dexamethasone (Dex)-loaded liposomes (Dex-DSLip), modified with dextran sulfate (DS), target macrophages via interaction with scavenger receptor A (SR-A). Simultaneously, crocin I (Cro) is loaded in the gel with a high loading capacity. The porous structure of Dex-DSLip/Cro@Gel successfully prolongs the retention time of both drugs and sustains the release of Dex and Cro. After intra-articular injection of Dex-DSLip/Cro@Gel in RA rats, the expression of inflammatory factors in the ankle joints was significantly reduced. Joint erythema and bone erosion were markedly alleviated. Through the synergistic effects of Dex and Cro, Dex-DSLip/Cro@Gel demonstrates targeted anti-inflammatory and antioxidation effects as well as mitigated bone erosion and long-term therapeutic effects for RA. This thermosensitive injectable nanocomposite hydrogel synergizes anti-inflammatory and antioxidation effects and targets the microenvironment in the joint, offering a new approach for RA treatment.

Injective hydrogel loaded with liposomes-encapsulated MY-1 promotes wound healing and increases tensile strength by accelerating fibroblast migration via the PI3K/AKT-Rac1 signaling pathway

Failed skin wound healing, through delayed wound healing or wound dehiscence, is a global public health issue that imposes significant burdens on individuals and society. Although the application of growth factor is an effective method to improve the pace and quality of wound healing, the clinically approved factors are limited. Parathyroid hormone (PTH) demonstrates promising results in wound healing by promoting collagen deposition and cell migration, but its application is limited by potentially inhibitory effects when administered continuously and locally. Through partially replacing and repeating the amino acid domains of PTH(1–34), we previously designed a novel PTH analog, PTH(3–34)(29–34) or MY-1, and found that it avoided the inhibitory effects of PTH while retaining its positive functions. To evaluate its role in wound healing, MY-1 was encapsulated in liposomes and incorporated into the methacryloyl gelatin (GelMA) hydrogel, through which an injectable nanocomposite hydrogel (GelMA–MY@Lipo, or GML) was developed. In vitro studies revealed that the GML had similar properties in terms of the appearance, microstructure, functional groups, swelling, and degradation capacities as the GelMA hydrogel. In vitro drug release testing showed a relatively more sustainable release of MY-1, which was still detectable in vivo 9 days post-application. When the GML was topically applied to the wound areas of rat models, wound closure as well as tensile strength were improved. Further studies showed that the effects of GML on wound repair and tensile strength were closely related to the promotion of fibroblast migration to the wound area through the controlled release of MY-1. Mechanically, MY-1 enhanced fibroblast migration by activating PI3K/AKT signaling and its downstream molecule, Rac1, by which it increased fibroblast aggregation in the early stage and resulting in denser collagen deposition at a later time. Overall, these findings demonstrated that the nanocomposite hydrogel system promoted skin wound healing and increased tensile strength, thus offering new potential in the treatment of wound healing.

Structure driven bio-responsive ability of injectable nanocomposite hydrogels for efficient bone regeneration

Injectable hydrogels are promising for treatment of bone defects in clinic owing to their minimally invasive procedure. Currently, there is limited emphasis on how to utilize injectable hydrogels to mobilize body's regenerative potential for enhancing bone regeneration. Herein, an injectable bone-mimicking hydrogel (BMH) scaffold assembled from nanocomposite microgel building blocks was developed, in which a highly interconnected microporous structure and an inorganic/organic (methacrylated hydroxyapatite and methacrylated gelatin) interweaved nano structure were well-designed. Compared with hydrogels lacking micro-nano structures or only showing microporous structure, the BMH scaffold enhanced the ingrowth of vessels and promoted the formation of dense cellular networks (including stem cells and M2 macrophages), across the entire scaffold at early stage after subcutaneous implantation. Moreover, the BMH scaffold could not only directly trigger osteogenic differentiation of the infiltrated stem cells, but also provided an instructive osteo-immune microenvironment by inducing macrophages into M2 phenotype. Mechanistically, our results reveal that the nano-rough structure of the BMH plays an essential role in inducing macrophage M2 polarization through activating mechanotransduction related RhoA/ROCK2 pathway. Overall, this work offers an injectable hydrogel with micro-nano structure driven bio-responsive abilities, highlighting harnessing body's inherent regenerative potential to realize bone regeneration.

An Injectable Nanocomposite IPN Hydrogel Based on Gelatin Methacrylate/Alginate/COF for Tissue Engineering Applications

An Injectable Nanocomposite IPN Hydrogel Based on Gelatin Methacrylate/Alginate/COF for Tissue Engineering Applications

Injectable Nanocomposite Hydrogels with Strong Antibacterial, Osteoinductive, and ROS-Scavenging Capabilities for Periodontitis Treatment.

Injectable antibacterial and osteoinductive hydrogels have received considerable attention for promoting bone regeneration owing to their versatile functionalities. However, a current hydrogel with antibacterial, osteoinductive, and antioxidant properties by a facile method for periodontitis treatment is still missing. To overcome this issue, we designed an injectable hydrogel system (GPM) composed of gelatin, Ti3C2Tx MXene nanosheets, and poly-l-lysine using a simple enzymatic cross-linking technique. Physicochemical characterization demonstrated that the GPM hydrogel matrix exhibited excellent stability, moderate tissue adhesion ability, and good mechanical behavior. The GPM hydrogels significantly inhibited the growth of Porphyromonas gingivalis, scavenged reactive oxygen species, attenuated inflammatory responses, and enhanced bone tissue regeneration. Intriguingly, the arrangement of the junctional epithelium, alveolar bone volume, and alveolar bone height in the GPM-treated periodontal disease group recovered to that of the healthy group. Therefore, our injectable hydrogel system with versatile functions may serve as an excellent tissue scaffold for the treatment of periodontitis.

Preparation of Short Collagen Nanofibers for Injectable Hydrogels: Comparative Assessment of Fragmentation Methods, Physicomechanical Properties, and Biocompatibility

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

Mussel inspired sequential protein delivery based on self-healing injectable nanocomposite hydrogel

Polysaccharide based self-healing and injectable hydrogels with reversible characteristics have widespread potential in protein drug delivery. However, it is a challenge to design the dynamic hydrogel for sequential release of protein drugs. Herein, we developed a novel mussel inspired sequential protein delivery dynamic polysaccharide hydrogel. The nanocomposite hydrogel can be fabricated through doping polydopamine nanoparticles (PDA NPs) into reversible covalent bond (imine bonds) crosslinked polymer networks of oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CEC), named PDA NPs@OHA-l-CEC. Besides multiple capabilities (i.e., injection, self-healing, and biodegradability), the nanocomposite hydrogel can achieve sustained and sequential protein delivery of vascular endothelial growth factor (VEGF) and bovine serum albumin (BSA). PDA NPs doped in hydrogel matrix serve dual roles, acting as secondary protein release structures and form dynamic non-covalent interactions (i.e., hydrogen bonds) with polysaccharides. Moreover, by adjusting the oxidation degree of OHA, the hydrogels with different crosslinking density could control overall protein release rate. Analysis of different release kinetic models revealed that Fickian diffusion drove rapid VEGF release, while the slower BSA release followed a Super Case II transport mechanism. The novel biocompatible system achieved sequential release of protein drugs has potentials in multi-stage synergistic drug deliver based on dynamic hydrogel.

Injectable Nanocomposite Immune Hydrogel Dressings: Prevention of Tumor Recurrence and Anti-Infection after Melanoma Resection.

Complex wound repair due to tumor recurrence and infection following tumor resection presents significant clinical challenges. In this study, a bifunctional nanocomposite immune hydrogel dressing, SerMA-LJC, is developed to address the issues associated with repairing infected damaged tissues and preventing tumor recurrence. Specifically, the immune dressing is composed of methacrylic anhydride-modified sericin (SerMA) and self-assembled nanoparticles (LJC) containing lonidamine (Lon), JQ1, and chlorine e6 (Ce6). In vitro and in vivo experiments demonstrate that the nanocomposite hydrogel dressing can trigger immunogenic cell death (ICD) and has a potent anti-tumor effect. Moreover, this dressing can mitigate the acidic microenvironment of tumor cells and suppress the overexpression of PD-L1 on the tumor cell surface, thereby altering the immunosuppressive tumor microenvironment and augmenting the anti-tumor immune response. Further, the RNA sequencing analysis revealed that the hydrogel dressing significantly impacts pathways associated with positive regulation of immune response, apoptotic process, and other relevant pathways, thus triggering a potent anti-tumor immune response. More importantly, the dressing generates a substantial amount of reactive oxygen species (ROS), which can effectively kill Staphylococcus aureus and promote infectious wound healing. In conclusion, this dual-function nanocomposite immune hydrogel dressing exhibits promise in preventing tumor recurrence and promoting infectious wound healing.

Injectable ultrasound-powered bone-adhesive nanocomposite hydrogel for electrically accelerated irregular bone defect healing

The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.

Tough, self-healing and injectable dynamic nanocomposite hydrogel based on gelatin and sodium alginate

Biomacromolecules based injectable and self-healing hydrogels possessing high mechanical properties have widespread potential in biomedical field. However, dynamic features are usually inversely proportional to toughness. It is challenging to simultaneously endow these properties to the dynamic hydrogels. Here, we fabricated an injectable nanocomposite hydrogel (CS-NPs@OSA-l-Gtn) stimultaneously possessing excellent autonomous self-healing performance and high mechanical strength by doping chitosan nanoparticles (CS-NPs) into dynamic polymer networks of oxidized sodium alginate (OSA) and gelatin (Gtn) in the presence of borax. The synergistic effect of the multiple reversible interactions combining dynamic covalent bonds (i.e., imine bond and borate ester bond) and noncovalent interactions (i.e., electrostatic interaction and hydrogen bond) provide effective energy dissipation to endure high fatigue resistance and cyclic loading. The dynamic hydrogel exhibited excellent mechanical properties like maximum 2.43 MPa compressive strength, 493.91 % fracture strain, and 89.54 kJ/m3 toughness. Moreover, the integrated hydrogel after injection and self-healing could withstand 150 successive compressive cycles. Besides, the bovine serum albumin embedded in CS-NPs could be sustainably released from the nanocomposite hydrogel for 12 days. This study proposes a novel strategy to synthesize an injectable and self-healing hydrogel combined with excellent mechanical properties for designing high-strength natural carriers with sustained protein delivery.

A sustainable and self-healable silk fibroin nanocomposite with antibacterial and drug eluting properties for 3D printed wound dressings.

The development of self-healable and 3D printable hydrogels with decent biocompatibility, mechanical durability, adhesiveness to tissues, and antibacterial activity is of great importance for wound healing applications. In this study, we present a sustainable and environmentally friendly composite hydrogel consisting of silk fibroin (SF), oxidized salep (OS), and kappa carrageenan nanoparticles (NPs) for efficient wound care. The injectable nanocomposite hydrogel is highly stretchable and exhibits strong tissue adhesiveness and self-healing response through Schiff-base cross-linking between OS and SF. The tunable shear-thinning viscoelastic properties of the hydrogel facilitate 3D bioprinting with excellent shape adaptability (97.7 ± 1.1% recovery), enabling the fabrication of complex-shaped constructs. In vitro release kinetics of tetracycline (TC) encapsulated in kappa carrageenan NPs indicate a distinctive Korsmeyer-Peppas profile, including an initial burst release followed by a triphasic pattern controlled by the embedded NPs within the hydrogel matrix. The composite hydrogel shows a remarkable broad-spectrum antibacterial activity with substantial zones of inhibition against S. aureus (34.00 ± 1.00 mm) and E. coli (27.60 ± 2.08 mm) after 24 h of incubation at 37 °C. The addition of TC further enhances the zones of inhibition by approximately 45% for S. aureus and 27% for E. coli. The control group without kappa NP incorporation shows no zone of inhibition, underscoring the critical role of the nanoparticles in imparting antibacterial activity to the hydrogel. Cytocompatibility assays show the high viability of fibroblast (L929) cells (>90%) in vitro. In vivo biocompatibility studies through subcutaneous implantation also do not show malignancy, infection, abscess, necrosis, epidermal or dermal modifications, or inflammation of the wounds after 14 days post-injection. H&E staining shows that the biodegradation of the developed hydrogel facilitates the growth of non-inflammatory cells, leading to the substitution of the injected hydrogel with autologous tissue. The detailed analyses affirm that the multifunctional injectable hydrogel with self-healing and antibacterial properties has high potential for wound healing and skin tissue engineering.

In Situ Gelling Hydroxypropyl Cellulose Formulation Comprising Cannabidiol-Loaded Block Copolymer Micelles for Sustained Drug Delivery.

Cannabidiol (CBD) is a natural terpenophenolic compound with known pharmacological activities, but the poor solubility of CBD in water limits its widespread use in medicine and pharmacy. Polymeric (nano)carriers demonstrated high potential for enhancing the solubility and therapeutic activity of lipophilic drugs such as CBD. Here, we report the elaboration of a novel hydroxypropyl cellulose (HPC)-based in situ gelling formulation for controlled delivery of CBD. In the first stage, nanosized polymeric micelles from poly(ethylene oxide)-block-poly(α-cinnamyl-ε-caprolactone-co-ε-caprolactone) (PEO-b-P(CyCL-co-CL) diblock copolymers) were used to increase the solubility of CBD in water. Different copolymers were assessed, and the carrier with the highest encapsulation efficiency (EE) and drug loading capacity (DLC) was selected for further elaboration of nanocomposite in situ gel formulations. Next, the sol-to-gel transition behavior of HPC as a function of K2SO4 concentration in the aqueous solution was investigated by microcalorimetry and dynamic oscillatory rheology, and the optimal formulation capable of forming a physical gel under physiological conditions was determined. Finally, injectable nanocomposite hydrogels comprising cannabidiol were fabricated, and their drug release profile and cytotoxicity against human tumor cell lines were evaluated. The in situ gels exhibited prolonged drug release over 12 h, controlled by gel erosion, and the cytotoxicity of formulated cannabidiol was comparable with that of a free drug.

An injectable nanocomposite hydrogel prevents postoperative tumor recurrence and wound infection via synergistic photothermal-chemo-therapy

HypothesisTumor recurrence, bacterial infection, and wound healing remain significant clinical challenges after skin-tumor resection. In this study, we tested the hypothesis that a multifunctional nanocomposite platform containing nanoparticles (NPs) with the photothermal agent IR820 and bioactive drug curcumin (Cur) would be able to prevent tumor recurrence, limit bacterial wound infections, and promote wound healing. ExperimentsIn this study, we developed a near-infrared light-activated nanocomposite hydrogel system (Hydrogel/Cur@IR820) by incorporating self-assembled NPs (Cur@IR820) in solutions containing Pluronic F127 modified with aldehyde groups (F127-CHO) and polyethyleneimine-grafted F127 (F127-PEI). FindingsThe Hydrogel/Cur@IR820 platform exhibited inherent multifunctional properties, including superior injectability, self-healing behavior, photothermal effects, and free radical scavenging ability. The Cur@IR820 NPs led to photonic hyperthermia and near-infrared (NIR)-triggered Cur release, which drove synergistic therapeutic effects against bacteria and tumor cells. Furthermore, the Hydrogel/Cur@IR820 system promoted wound repair and tissue regeneration by reducing inflammation through the antioxidant properties of Cur. Overall, the results of this study have clinical implications for inhibiting tumor growth, treating bacterial infections, and accelerating tissue regeneration.

Decoding Macrophage Subtypes to Engineer Modulating Hydrogels for the Alleviation of Intervertebral Disk Degeneration.

A major pathological basis for low back pain is intervertebral disk degeneration, which is primarily caused by the degeneration of nucleus pulposus cells due to imbalances in extracellular matrix (ECM) anabolism and catabolism. The phenotype of macrophages in the local immune microenvironment greatly influences the balance of ECM metabolism. Therefore, the control over the macrophage phenotype of the ECM is promising to repair intervertebral disk degeneration. Herein, the preparation of an injectable nanocomposite hydrogel is reported by embedding epigallocatechin-3-gallate-coated hydroxyapatite nanorods in O-carboxymethyl chitosan cross-linked with aldehyde hyaluronic acid that is capable of modulating the phenotype of macrophages. The bioactive components play a primary role in repairing the nucleus pulposus, where the hydroxyapatite nanorods can promote anabolism in the ECM through the nucleopulpogenic differentiation of mesenchymal stem cells. In addition, epigallocatechin-3-gallate can decrease catabolism in the ECM in nucleus pulposus by inducing M2 macrophage polarization, which exists in normal intervertebral disks and can alleviate degeneration. The nanocomposite hydrogel system shows promise for the minimally invasive and effective treatment of intervertebral disk degeneration by controlling anabolism and catabolism in the ECM and inhibiting the IL17 signaling pathway (M1-related pathway) in vitro and in vivo.

Self-healing nanocomposite hydrogels based on chitosan/ modified polyethylene glycol/graphene

The aim of this research is to prepare self-healing injectable nanocomposite hydrogels based on benzaldehyde-modified polyethylene glycol and chitosan, reinforced with graphene oxide (GO) for the delivery of pomegranate extract (PG) for hard tissue engineering. For this purpose, polyethylene glycol (PEG) was first modified by an aldehyde agent and mixed with chitosan to form hydrogels based on reversible Schiff-Base linkages. Nanocomposites were prepared with the addition of 0.5, 1.0, 1.5, and 2.0 wt% GO to the hydrogels. Then, PG was loaded into the final nanocomposite hydrogels as the drug model to promote cell proliferation and chondrogenesis. The scanning electron microscopy (SEM) images indicated that the incorporation of GO into the hydrogels increased the average pore size from 261 to 403 µm, resulting in a favorable porous structure. The results also showed an enhancement in the elastic properties as well as the compressive strength of the nanocomposite hydrogels with increasing GO content. The drug release profile followed a power-law kinetics, in which, the content of PG and GO affected the release rate. According to self-healing and injection tests, all the hydrogels had good injection and self-healing capabilities. The incorporation of GO into the hydrogel increased antibacterial properties to more than 99%. The in vitro assay indicated that PG loading provided a suitable environment for the growth and survival of cells on the hydrogels. Therefore, the designed system is a promising framework for the local delivery of pharmaceuticals for hard tissue engineering.

Self-Healable and Injectable Nanocomposite Hydrogel Loading Iron-Doped Carbon Dots for Synergistic Antibacterial Peptide-Photothermal-Photodynamic Antibacterial Therapy

Self-Healable and Injectable Nanocomposite Hydrogel Loading Iron-Doped Carbon Dots for Synergistic Antibacterial Peptide-Photothermal-Photodynamic Antibacterial Therapy

Injectable On-Demand Pulsatile Drug Delivery Hydrogels Using Alternating Magnetic Field-Triggered Polymer Glass Transitions.

Remote-controlled pulsatile or staged release has significant potential in a wide range of therapeutic treatments. However, most current approaches are hindered by the low resolution between the on- and off-states of drug release and the need for surgical implantation of larger controlled-release devices. Herein, we describe a method that addresses these limitations by combining injectable hydrogels, superparamagnetic iron oxide nanoparticles (SPIONs) that heat when exposed to an alternating magnetic field (AMF), and polymeric nanoparticles with a glass transition temperature (Tg) just above physiological temperature. Miniemulsion polymerization was used to fabricate poly(methyl methacrylate-co-butyl methacrylate) (p(MMA-co-BMA)) nanoparticles loaded with a model hydrophobic drug and tuned to have a Tg value just above physiological temperature (∼43 °C). Co-encapsulation of these drug-loaded nanoparticles with SPIONs inside a carbohydrate-based injectable hydrogel matrix (formed by rapid hydrazone cross-linking chemistry) enables injection and immobilization of the nanoparticles at the target site. Temperature cycling facilitated a 2.5:1 to 6:1 on/off rhodamine release ratio when the nanocomposites were switched between 37 and 45 °C; release was similarly enhanced by exposing the nanocomposite hydrogel to an AMF to drive heating, with enhanced release upon pulsing observed even 1 week after injection. Coupled with the apparent cytocompatibility of all of the nanocomposite components, these injectable nanocomposite hydrogels are promising as minimally invasive but remotely actuated release delivery vehicles capable of complex release kinetics with high on-off resolution.

Nanocomposite hydrogel based on chitosan/laponite for sealing and repairing tracheoesophageal fistula

Tracheoesophageal fistula (TEF) is an abnormal connection between the trachea and esophagus that severely impairs quality of life. Current treatment options have limitations, including conservative treatment, surgical repair, and esophageal stent implantation. Here, we introduced laponite (LP) nano-clay to improve chitosan-based hydrogels' rheological properties and mechanical properties and developed an endoscopically injectable nanocomposite shear-thinning hydrogel to seal and repair fistulas as an innovative material for the treatment of TEF. Excellent injectability, rheological properties, mechanical strength, self-healing, biodegradability, biocompatibility, and tissue repair characterize the new hydrogel. The introduction of LP nano-clay improves the gel kinetics problem of hydrogels to realize the sol–gel transition immediately after injection, avoiding gel flow to non-target sites. The addition of LA nano-clay can significantly improve the rheological properties and mechanical strength of hydrogels, and hydrogel with LP content of 3 % shows better comprehensive performance. The nanocomposite hydrogel also shows good cytocompatibility and can promote wound repair by promoting the migration of HEEC cells and the secretion of VEGF and FGF. These findings suggest that this nanocomposite hydrogel is a promising biomaterial for TEF treatment.

Bioinspired self-healing injectable nanocomposite hydrogels based on oxidized dextran and gelatin for growth-factor-free bone regeneration

Hydrogels with great biocompatibility, biodegradability, and mechanical properties, combined with osteoconductivity, osteoinductivity, and osteointegration as biomaterials for bone regeneration without adding exogenous growth factors and cells are highly appealing but challenging. Here, inspired by organic-inorganic analogues of natural bone tissue and the adhesion chemistry of mussels, nanocomposite hydrogels with self-healing, injectable, adhesive, antioxidant, and osteoinductive properties (termed GO-PHA-CPs) were constructed by Schiff base cross-linking between dopamine-modified gelatin (Gel-DA) and oxidized dextran (ODex). Furthermore, the hydrogel network was enhanced by the introduction of polydopamine-functionalized nanohydroxyapatite (PHA) by improving the interfacial compatibility between the rigid inorganic particles and the flexible hydrogel matrix. Bioactive cod peptides (CPs) with osteogenic activity from Atlantic cod were further incorporated into the nanocomposite hydrogel. As a result, the multicomponent nanocomposite hydrogel favored the adhesion and spreading of MC3T3-E1 cells. The increased ALP activity suggested that GO-PHA-CPs hydrogels contributed to the osteogenic differentiation of MC3T3-E1 cells. The suitability of GO-PHA-CPs hydrogels for enhancing bone regeneration in vivo was further confirmed by the rat femoral defect model. Our results indicate that the multifunctional GO-PHA-CPs nanocomposite hydrogels without growth factors are a promising and effective candidate material for bone regeneration.

Hyaluronic acid-based injectable nanocomposite hydrogels with photo-thermal antibacterial properties for infected chronic diabetic wound healing

A hydrogel wound dressing with a single functionality fails to meet the requirements for successful clinical treatment of chronic diabetic wounds that generally possess complicated microenvironments. A multifunctional hydrogel is thus highly desirable for improved clinical treatment. For this purpose, we reported herein construction of an injectable nanocomposite hydrogel with self-healing and photo-thermal properties as an antibacterial adhesive via dynamic Michael addition reaction and electrostatic interactions among three building moieties, i.e., catechol and thiol-modified hyaluronic acid (HA-CA and HA-SH), poly(hexamethylene guanidine) (PHMG), and black phosphorus nanosheets (BPs). An optimized hydrogel formulation eliminated over 99.99 % of bacteria (E. coli and S. aureus) and exhibited a free radical scavenging capability >70 % as well as photo-thermal properties in addition to viscoelastic characteristics, degradation properties in vitro, good adhesion and self-adaptation capacity. Wound healing experiments in vivo further confirmed the better performance of the developed hydrogels than that of a commercially available dressing (Tegaderm™) in promoting the healing of infected chronic wounds by preventing wound infection, decreasing inflammation, supporting collagen deposition, facilitating angiogenesis, and improving granulation tissues formation in the wound sites. Overall, the HA-based injectable composite hydrogels developed herein represent promising multifunctional wound dressings for infected diabetic wound repair.