Mingying Gao

Achieving rapid and scar-free wound repair is a key goal in the field of regenerative medicine. Herein, a dynamically Schiff base-crosslinked hydrogel (F/R gel) with phase-adaptive regulating functions is constructed to integratedly promote rapid re-epithelization with suppressed scars on chronic infected wounds. Specifically, the gel effectively eliminates multidrug-resistant bacterial biofilm at infection stage via antimicrobial activity of ε-polylysine firstly dissociated from hydrogel matrix in infectious microenvironment, and interrupts the severe oxidative stress-inflammation cycle at wound site by the released ceria nanozyme, thus stimulating a pro-regenerative environment to ensure tissue repair. Subsequently, fibroblast growth factor/c-Jun siRNA co-loaded microcapsules gradually disintegrate to release drugs, facilitating neoangiogenesis and cell proliferation but simultaneously blocking c-Jun overexpression for fibrotic scar suppression. Notably, the F/R gel facilitates normal-like skin regeneration with no perceptible scars formed on infected male mouse wound and female rabbit ear wound models. Our work offers a promising regenerative strategy emphasizing immunomodulatory and fibroblast subtype modulation for scarless wound repair. It is challenging to achieve scar-free repair of chronic wounds as they often feature the occurrence of multiple healing phases in an unpredictable and nonlinear manner. Here, the authors report a healing phase-adaptive regulating hydrogel that exhibits hierarchically delivering performance for programmed modulation of chronic infected wounds.

Rheumatoid arthritis (RA) is a common chronic disease dominated by inflammatory synovitis, which is characterized with hyperplastic synovium, up-regulated matrix metalloproteinase (MMP) expression, hypoxic joint cavity and excessive reactive oxygen species (ROS) accumulation. Such local adverse microenvironment in RA joints further exacerbates the infiltration of synovial inflammatory cells, especially M1-type macrophages. Regulating intra-articular pathological conditions, eliminating excess M1 macrophages or converting them to an anti-inflammatory M2 phenotype may break the vicious progression circle. Herein, we develop a multi-stimulus responsive lipogel as effective platform to relieve RA symptoms and promote articular cartilage recovery via reversing its inflammatory microenvironment. The injectable lipogel is fabricated by loading polydopamine nanoparticles and methotrexate into a thermosensitive gel, and intra-articularly injected to form the therapeutic depot (PDA/MTX@TSG) in situ. The gel degrades slowly under esterase hydrolysis, and maintains sustained drug release in physiological conditions. Meanwhile, it can 1) induce a reversible gel-sol phase transition upon mild photothermal treatment (external NIR light control), and 2) specifically respond to MMP-rich RA microenvironment (internal enzymatic hydrolysis effect). Such stimulus-responsive system can deliver therapeutic components in a controllable manner, and significantly reverse adverse inflammatory microenvironment of RA joints through ROS eliminating, hypoxia alleviating, and M1-M2 macrophage polarization effects. Animal experiments indicate that observable RA relief and joint repair are realized after a single lipogel injection combined with NIR irradiation. Our study highlights the importance of altering local RA microenvironment via anti-inflammatory macrophage polarization, and therefore presents a potent therapeutic strategy for RA treatment in clinical intervention.

Abstract Effective wound repair and preventive strategies against scarring remain challenging especially for chronic refractory wounds, as aberrant healing often encounters with persistent bacterial infection, extensive inflammatory response, impaired angiogenesis, and fibrotic scar formation. Herein, a photoliquefiable hydrogel dressing (denoted as PCS gel) is proposed as promising therapeutic strategy for rapid anti‐scar skin regeneration of refractory wounds. Specifically, the gel exerts robust antibacterial effect via mild thermogenesis for multidrug‐resistant biofilm eradication, and timely regulates tissue redox homeostasis. Upon efficient alleviation of local immoderate inflammation, PCS gel fosters a favorable pro‐regenerative microenvironment by bridging swift transition of the inflammatory stage to the proliferative stage, and thus significantly promotes neoangiogenesis as well as epithelialization. Importantly, the gel simultaneously alters pro‐regenerative fibroblast subpopulations by effective suppression of CD36 receptor during this stage, and hence blocks JUN overexpression‐mediated dermal fibrotic scarring. Notably, by thorough testing on both murine infected wound models (including acute wounds, diabetic chronic wounds) and rabbit ear hyperplastic scar wound model, PCS gel aided by thermogenesis facilitates rapid normal skin‐like epithelial closure with no perceptible hyperplastic scars. Therefore, our work emphasizes the promising regenerative strategy of immunomodulation and fibroblast lineage regulation by the PCS gel platform for rapid anti‐scar wound repair.

To investigate the value of bracketless invisible orthodontic treatment combined with restoration in patients with anterior esthetic restoration. Sixty-two patients requiring esthetic restoration of anterior teeth admitted to our hospital from May 2019 to August 2022 were selected and divided into observation group and control group according to random number table, with 31 cases in each group. The patients in the control group were treated with repair, while patients in the observation group were treated with bracketless invisible correction treatment combined with repair. The patients in both groups were treated with repair. After 2 weeks, dental esthetics, periodontal index related parameters, patients’ esthetic acceptance of restorations, and satisfaction were compared. The aesthetic restoration effect of teeth in the observation group was significantly better than that in the control group after treatment, and the difference was statistically significant (P < 0.05). There was no significant difference in GI, SPD, PLI, and SBI levels before and after treatment between the two groups (P > 0.05). The acceptance rate of prosthesis aesthetics in the observation group was 100.00%, which was significantly higher than that in the control group (83.87%), and the difference was statistically significant (P < 0.05). The satisfaction scores of restoration color, shape and coordination with adjacent teeth in the observation group were higher than those in the control group, and the differences were statistically significant (P < 0.05). Compared with simple restorative treatment, combined with bracketless invisible orthodontic treatment helps to further improve the esthetic restoration effect of anterior teeth, has less impact on the periodontal health of patients, and has higher patient acceptance and satisfaction.