Injectable conductive hydrogel remodeling microenvironment and mimicking neuroelectric signal transmission after spinal cord injury.

Severe spinal cord injury (SCI) leads to dysregulated neuroinflammation and cell apoptosis, resulting in axonal die-back and the loss of neuroelectric signal transmission. While biocompatible hydrogels are commonly used in SCI repair, they lack the capacity to support neuroelectric transmission. To overcome this limitation, we developed an injectable silk fibroin/ionic liquid (SFMA@IL) conductive hydrogel to assist neuroelectric signal transmission after SCI in this study. The hydrogel can form rapidly in situ under ultraviolet (UV) light. The mechanical supporting and neuro-regenerating properties are provided by silk fibroin (SF), while the conductive capability is provided by the designed ionic liquid (IL). SFMA@IL showed attractive features for SCI repair, such as anti-swelling, conductivity, and injectability. In vivo, SFMA@IL hydrogel used in rats with complete transection injuries was found to remodel the microenvironment, reduce inflammation, and facilitate neuro-fiber outgrowth. The hydrogel also led to a notable decrease in cell apoptosis and the achievement of scar-free wound healing, which saved 45.6 ± 10.8 % of spinal cord tissue in SFMA@IL grafting. Electrophysiological studies in rats with complete transection SCI confirmed SFMA@IL's ability to support sensory neuroelectric transmission, providing strong evidence for its signal transmission function. These findings provide new insights for the development of effective SCI treatments.

A nano-composite hyaluronic acid-based hydrogel efficiently antibacterial and scavenges ROS for promoting infected diabetic wound healing.

Diabetic wound infection brings chronic pain to patients and the therapy remains a crucial challenge owing to the disruption of the internal microenvironment. Herein, we report a nano-composite hydrogel (ZnO@HN) based on ZnO nanoparticles and a photo-trigging hyaluronic acid which is modified by o-nitrobenzene (NB), to accelerate infected diabetic wound healing. The diameter of the prepared ZnO nanoparticle is about 50 nm. X-ray photoelectron spectroscopy (XPS) analysis reveals that the coordinate bond binds ZnO in the hydrogel, rather than simple physical restraint. ZnO@HN possesses efficient antioxidant capacity and it can scavenge DPPH about 40 % in 2 h and inhibit H2O2 >50 % in 8 h. The nano-composite hydrogel also exhibits satisfactory antibacterial capacity (58.35 % against E. coli and 64.03 % against S. aureus for 6 h). In vitro tests suggest that ZnO@HN is biocompatible and promotes cell proliferation. In vivo experiments reveal that the hydrogel can accelerate the formation of new blood vessels and hair follicles. Histological analysis exhibits decreased macrophages, increased myofibroblasts, downregulated TNF-α expression, and enhanced VEGFA expression during wound healing. In conclusion, ZnO@HN could be a promising candidate for treating intractable infected diabetic skin defection.

An injectable thermosensitive hyaluronic acid/pluronic F-127 hydrogel for deep penetration and combination therapy of frozen shoulder.

Frozen shoulder (FS) is a common and progressive shoulder disorder that causes glenohumeral joint stiffness, characterized by inflammation and fibrosis. The treatment options are quite limited, and the therapeutic response is hindered by the fibrous membrane formed by excessive collagen and the rapid removal by synovial fluid. To address these challenges, we designed a hyaluronic acid/Pluronic F-127 (HP)-based injectable thermosensitive hydrogel as a drug carrier loaded with dexamethasone and collagenase (HPDC). We screened for an optimal HP hydrogel that can sustain drug release for approximately 10 days both in vitro and in vivo. In the meanwhile, we found that HP hydrogel could inhibit the proliferation and diminish the adhesion capacity of rat synovial cells induced by transforming growth factor-ß1. Furthermore, using an established immobilization rat model of FS, intra-articular injection of HPDC significantly improved joint range of motion compared to medication alone. Relying on sustained drug release, the accumulated collagen fibers were degraded by collagenase to promote the deep delivery of dexamethasone. These findings showed a positive combined treatment effect of HPDC, providing a novel idea for the comprehensive treatment of FS.

PEGDA/HA mineralized hydrogel loaded with Exendin4 promotes bone regeneration in rat models with bone defects by inducing osteogenesis.

Scaffolds with osteogenic differentiation function play an important role in the healing process of bone defects. Here, we designed a high strength Poly(ethyleneglycol) diacrylate/Hydroxyapatite (PEGDA/HA) mineralized hydrogel loaded with Exendin4 for inducing osteogenic differentiation. In this study, PEGDA hydrogel was prepared by photo initiating method. PEGDA/HA mineralized hydrogel was prepared by in-situ precipitation method, and Exendin4 was loaded by gel adsorption. The effects of different calcium and phosphorus concentrations on the strength and Exendin4 release of PEGDA/HA hydrogels were investigated. Rat models of bone defect were made and randomly divided into 5 groups. The experimental group was implanted with PEGDA hydrogel, Exendin4-PEGDA hydrogel, PEGDA/HA mineralized hydrogel, Exendin4-PEGDA/HA mineralized hydrogel, and no materials were implanted in the blank control group. Computed tomography (CT) and histology were observed 4 and 8 weeks after operation. Our results revealed that the PEGDA/HA mineralized hydrogel had porous structure, high mechanical strength and good biocompatibility. In vitro release test showed that the mineralized hydrogel exhibited good sustained release profile within 20 d. The animal experiments showed that the mineralized hydrogel accelerated the formation of new bone after 4 and 8 weeks, and formed a seamless union on the defected bone area after 8 weeks. In conclusions, The Exendin4-PEGDA/HA mineralized hydrogel can effectively repair bone defects in rats, and it is expected to be used as a biomaterial for human bone tissue repair.

Microwave hyperthermia-responsible flexible liposomal gel as a novel transdermal delivery of methotrexate for enhanced rheumatoid arthritis therapy.

Methotrexate (MTX) as an anti-inflammatory drug for the treatment of rheumatoid arthritis (RA) through oral and injectable administration is still problematic in the clinic. Herein, a MTX-loaded thermal-responsible flexible liposome (MTFL) incorporated within a carbomer-based gel was prepared as a novel transdermal agent (MTFL/Gel) for effective treatment of RA. It was found that MTFL had an average size of approximately 90 nm, which could rapidly release the drug under thermal conditions. The prepared MTFL/Gel could remarkably increase the MTX skin permeation as compared with free MTX, which was possibly due to the deformable membrane of flexible liposomes. Moreover, the results suggested MTFL/Gel could lead to a remarkably enhanced RA treatment when in combination with microwave hyperthermia. The superior ability of MTFL/Gel to alleviate RA response was attributed to the excellent skin permeation, thermal-responsible drug release, and synergistic anti-arthritic effect of MTX chemotherapy and microwave-induced hyperthermia therapy. Overall, the MTFL/Gel with dual deformable and thermal-responsible performances could be used as a novel promising transdermal agent for enhanced treatment of RA.