Modulation of macrophage polarization by secondary cross-linked hyaluronan-dopamine hydrogels.

The inflammatory response plays a critical role in standard tissue repair processes, wherein active modulation of macrophage polarization is necessary for wound healing. Dopamine, a mussel-inspired bioactive material, is widely involved in wound healing, neural/bone/myocardial regeneration, and more. Recent studies indicated that dopamine-modified biomaterials can potentially alter macrophages polarization towards a pro-healing phenotype, thereby enhancing tissue regeneration. Nevertheless the immunoregulatory activity of dopamine on macrophage polarization remains unclear. This study introduces a novel interpenetrating hydrogel to bridge this research gap. The hydrogel, combining varying concentrations of oxidized dopamine with hyaluronic acid hydrogel, allows precise regulation of mechanical properties, antioxidant bioactivity, and biocompatibility. Surprisingly, both in vivo and in vitro outcomes demonstrated that dopamine concentration modulates macrophage polarization, but not linearly. Lower concentration (2 mg/mL) potentially decrease inflammation and facilitate M2 type macrophage polarization. In contrast, higher concentration (10 mg/mL) exhibited a pro-inflammatory tendency in the late stages of implantation. RNA-seq analysis revealed that lower dopamine concentrations induced the M1/M2 transition of macrophages by modulating the NF-κB signaling pathway. Collectively, this research offers valuable insights into the immunoregulation effects of dopamine-integrated biomaterials in tissue repair and regeneration.

Guanidinylated bioactive chitosan-based injectable hydrogels with pro-angiogenic and mechanical properties for accelerated wound closure.

Wound healing is a complex process involving the concerted action of many genes and signaling pathways, with angiogenesis being crucial for expediting wound closure. Dressings that possess pro-angiogenic properties are increasingly recognized as attractive candidates for wound care. Drawing inspiration from the active closure of wounds in embryos, we have developed a thermo-responsive hydrogel with mechanoactive properties, combining vascular regeneration and skin wound contraction to accelerate healing. The significant improvement in vascular reconstruction is attributed to the synergistic effect of arginine and deferoxamine (DFO) released from the hydrogels. Additionally, the contraction force of the hydrogel actively promotes skin closure in wounds. Remarkably, groups treated with hydroxybutyl chitosan methacrylate combined with arginine (HBC_m_Arg/DFO) exhibited increased vascularization, and greater wound maturity, leading to enhanced healing. These results highlight the synergistic impact of pro-angiogenic and mechanical properties of the HBC_m_Arg/DFO hydrogel in accelerating wound healing in rats.

Hybrid Electrically Conductive Hydrogels with Local Nerve Growth Factor Release Facilitate Peripheral Nerve Regeneration.

It is challenging to treat peripheral nerve injury (PNI) clinically. As the gold standard for peripheral nerve repair, autologous nerve grafting remains a critical limitation, including tissue availability, donor-site morbidity, immune rejection, etc. Recently, conductive hydrogels (CHs) have shown potential applications in neural bioengineering due to their good conductivity, biocompatibility, and low immunogenicity. Herein, a hybrid electrically conductive hydrogel composed of acrylic acid derivatives, gelatin, and heparin with sustained nerve growth factor (NGF) release property was developed. The rat sciatic nerve injury (SNI) model (10 mm long segment defect) was used to investigate the efficacy of these hydrogel conduits in facilitating peripheral nerve repair. The results showed that the hydrogel conduits had excellent conductivity, mechanical properties, and biocompatibility. In addition, NGF immobilized in the hydrogel conduits had good sustained release characteristics. Finally, functional recovery and electrophysiological evaluations, together with histological analysis, indicated that the hydrogel conduits immobilizing NGF had superior effects on motor recovery, axon growth, and remyelination, thereby significantly accelerating the repairing of the sciatic nerve. This study demonstrated that hybrid electrically conductive hydrogels with local NGF release could be effectively used for PNI repair.

Antibacterial-Antioxidative Thiolated Gelatin/Methacrylated Silk Fibroin Hydrogels with Nitric Oxide Release Catalyzed by Metal-Polyphenol Nanoparticles for MRSA-Infected Wound Healing.

Chronic wound infection often leads to irregular tissue closure and accompanies delayed healing and economy issues. Developing an ideal wound dressing that can control the occurrence of antibacterial infections and biological responses is highly desirable. In this study, a multifunctional hybrid hydrogel (GS@EG-Cu-CA NPs) containing synthesized thiolated gelatin, methacrylated silk fibroin, and (-)-epigallocatechin gallate-copper ionic-carrageenan nanoparticles (EG-Cu-CA NPs) was engineered by a thio-ene click reaction. The metal-polyphenol EG-Cu-CA NPs were encapsulated with kappa-carrageenan to enhance its aqueous-soluble, mechanical, and bioactive properties and endowed the hydrogel dressing with fascinating antibacterial, antioxidation, and nitric oxide (NO) generation by catalyzing. The hybrid hydrogels also illustrated a favorable cytocompatibility. Benefiting from the thio-ene click reaction, the hybrid hydrogels were injected and photocured rapidly in situ to cover an irregular wound. In an SD rat full-thickness skin-wound-infected model, the methicillin-resistant Staphylococcus aureus-infected wound covered with GS@EG-Cu-CA NPs was almost completely healed after 10 days. This study presents a facile design of hydrogel dressing incorporating metal-polyphenol nanoparticles, which demonstrates a promising potential way for dealing with effective wound infection management and other complicated wound healings.

Mxene Reinforced Supramolecular Hydrogels with High Strength, Stretchability, and Reliable Conductivity for Sensitive Strain Sensors.

Conductive hydrogels used as electronics have received much attention due to their great flexibility and stretchability. However, the fabrication of ideal conductive hydrogels fulfilling the excellent mechanical properties and outstanding sensitivity remains a great challenge until now. Moreover, high sensitivity and broad linearity range are pivotal for the feasibility and accuracy of hydrogel sensors. In this study, a conductive supramolecular hydrogel is engineered by directly mixing the aqueous dispersion of MXene with the precursor of N-acryloyl glycinamide (NAGA) monomer and then rapidly photo cross-linked by UV irradiation. The resultant PNAGA/MXene hydrogel-sensors exhibit high mechanical strength (4.8 MPa), great stretchability (630%), and excellent durability. The conductive hydrogel-based sensor presents excellent conductivity (17.3 S m-1 ) and a wide scope of linear dependence of sensitivity on strain (0%-125%, gauge factor = 2.05). It displays reliable detection of various motions, including repeated subtle movements and large strain. It also shows good degradation in vitro and antifouling capability. This work may provide a simple and promising platform for engineering conductive supramolecular hydrogels with integrated high performance aiming for smart wearable electronics, electronic skin, soft robots, and human-machine interfacing.

Macroporous methacrylated hyaluronic acid hydrogel with different pore sizes forin vitroandin vivoevaluation of vascularization.

Vascularization of thick hydrogel scaffolds is still a big challenge, because the submicron- or nano-sized pores seriously restrict endothelial cells adhesion, proliferation and migration. Therefore, porous hydrogels have been fabricated as a kind of promising hydrous scaffolds for enhancing vascularization during tissue repairing. In order to investigate the effects of pore size on vascularization, macroporous methacrylated hyaluronic acid (HAMA) hydrogels with different pore sizes were fabricated by a gelatin microspheres (GMS) template method. After leaching out GMS templates, uniform and highly interconnected macropores were formed in hydrogels, which provided an ideal physical microenvironment to induce human umbilical vein endothelial cells (HUVECs) migration and tissue vascularization.In vitroresults revealed that macroporous hydrogels facilitated cells proliferation and migration compared with non-macroporous hydrogels. Hydrogels with middle pore size of 200-250 µm (HAMA250 hydrogels) supported the best cell proliferation and furthest 3D migration of HUVECs. The influences of pore sizes on vascularization were then evaluated with subcutaneous embedding.In vivoresults illustrated that HAMA250 hydrogels exhibited optimum vascularization behavior. Highest number of newly formed blood vessels and expression of CD31 could be found in HAMA250 hydrogels rather than in other hydrogels. In summary, our results concluded that the best pore size for endothelial cells migration and tissue vascularization was 200-250 µm. This research provides a new insight into the engineering vascularized tissues and may find utility in designing regenerative biomaterial scaffolds.

Preparation and characterization of a dual cross-linking injectable hydrogel based on sodium alginate and chitosan quaternary ammonium salt.

The development of cheap and easily available injectable hydrogel is an urgent problem in the field of biomedical engineering. Herein, we used chitosan quaternary ammonium salt and sodium alginate to prepare a dual crosslinking hydrogel. The hydrogel formed in-situ crosslinking and can be injected continuously. Interestingly, the formed hydrogel possessed a homogeneous 3D network structure and exhibited reasonable mechanical properties. Moreover, the hydrogels had excellent injectability, and the compression strength of the hydrogel (Gel-0.5) was up to 27.65 kPa. Additionally, the hydrogel showed good biocompatibility that evaluated by cytotoxicity. Notably, the hydrogel was nontoxic toward NIH-3T3 cells. In summary, the hydrogel we produced can be used as an ideal biomaterial for further applications in the field of biomedical engineering.