Enhancing diabetic wound healing through anti-bacterial and promoting angiogenesis using dual-functional slow-release microspheres-loaded dermal scaffolds.

Bacterial infections and the degeneration of the capillary network comprise the primary factors that contribute to the delayed healing of diabetic wounds. However, treatment modalities that cater to effective diabetic wounds healing in clinical settings are severely lacking. Herein, a dual-functional microsphere carrier was designed, which encapsulates polyhexamethylene biguanide (PHMB) or recombinant human vascular endothelial growth factor (rhVEGF) together. The in vitro release experiments demonstrated that the use of the microspheres ensured the sustained release of the drugs (PHMB or rhVEGF) over a period of 12 days. Additionally, the integration of these controlled-release microspheres into a dermal scaffold (DS-PLGA@PHMB/rhVEGF) imbued both antibacterial and angiogenic functions to the resulting material. Accordingly, the DS-PLGA@PHMB/rhVEGF scaffold exhibited potent antibacterial properties, effectively suppressing bacterial growth and providing a conducive environment for wound healing, thereby addressing the drawbacks associated with the susceptibility of rhVEGF to deactivation in inflammatory conditions. Additionally, the histological analysis revealed that the use of the DS-PLGA@PHMB/rhVEGF scaffold accelerated the process of wound healing by inhibiting inflammatory reactions, stimulating the production of collagen formation, and enhancing angiogenesis. This provides a novel solution for enhancing the antibacterial and vascularization capabilities of artificial dermal scaffolds, providing a beacon of hope for improving diabetic wound healing.

New insights into immune cells in cancer immunotherapy: from epigenetic modification, metabolic modulation to cell communication.

Cancer is one of the leading causes of death worldwide, and more effective ways of attacking cancer are being sought. Cancer immunotherapy is a new and effective therapeutic method after surgery, radiotherapy, chemotherapy, and targeted therapy. Cancer immunotherapy aims to kill tumor cells by stimulating or rebuilding the body's immune system, with specific efficiency and high safety. However, only few tumor patients respond to immunotherapy and due to the complex and variable characters of cancer immune escape, the behavior and regulatory mechanisms of immune cells need to be deeply explored from more dimensions. Epigenetic modifications, metabolic modulation, and cell-to-cell communication are key factors in immune cell adaptation and response to the complex tumor microenvironment. They collectively determine the state and function of immune cells through modulating gene expression, changing in energy and nutrient demands. In addition, immune cells engage in complex communication networks with other immune components, which are mediated by exosomes, cytokines, and chemokines, and are pivotal in shaping the tumor progression and therapeutic response. Understanding the interactions and combined effects of such multidimensions mechanisms in immune cell modulation is important for revealing the mechanisms of immunotherapy failure and developing new therapeutic targets and strategies.

Superficial Circumflex Iliac Artery Perforator Flap with Bilobed Design for the Donor Defect after Wrap-Around Flap Transfer Reconstruction.

OBJECTIVE: The repair of great toe donor site defect after wrap-around flap transfer is still controversial. The bilobed superficial circumflex iliac artery perforator (SCIP) flap can improve the aesthetics of the great toe while maintaining its function. Thus, this study aimed to report our experience in the reconstruction of big toe donor site defects with the bilobed SCIP flap and describe the clinical outcomes. METHODS: This study was a retrospective trial. From May 2017 to May 2020, 13 patients with the great toe donor site defect after wrap-around flap transfer were included in this study. The average age of the patients was 44 years (range, 23-60 years). All patients received free bilobed SCIP flaps to reconstruct the donor site defect of the great toe. Relevant clinical features were recorded preoperatively. The thickness and design of the SCIP flap and the harvesting layer of the flap were measured during the operation. The survival rate of flaps and skin grafts and the incidence of infection were recorded after operation. At follow-up, donor site complications and postoperative outcomes were evaluated. RESULTS: In all cases, the SCIP flap covering the donor site of the great toe survived. All patients were followed up for 24-40 months (mean, 30.5 months). The average thickness of the SCIP flap was 0.38cm. All SCIP flaps were harvested from the superficial fascial layer except for three obese patients. The thin SCIP flap had a bilobed design with no further defatting procedures. Postoperatively, the great toe-nail flap donor site regained its original appearance without bloating or flap necrosis. There was a hidden linear scar in the groin donor site, which did not affect hip joint movement. All patients were satisfied with the aesthetics of the surgical site. CONCLUSION: The SCIP flap with bilobed design for repairing the donor defect of the great toe after wrap-around flap transfer is a kind of surgical method with excellent contour, meeting the requirements of function and aesthetics.

A Novel Bifunctional Nanoplatform with Aggregation-Induced Emission Property for Efficient Photodynamic Killing of Bacteria and Wound Healing.

Background: Photodynamic antimicrobial therapy (PDAT) has been extensively studied because of its potential applications such as precise controllability, high spatiotemporal accuracy, and non-invasiveness. More importantly, it is difficult for bacteria to develop resistance to the aforementioned PDATs. However, the selectivity of traditional PDAT methods to bacteria is generally poor, so it has been proposed to introduce positively charged components such as quaternary ammonium salts to enhance the targeting of bacteria; however, they always possess high toxicity to normal cells. As a result, measures should be taken to enhance the targeting of bacteria and avoid side effects on normal cells. Methods and Results: In our work, we creatively design a nanoplatform with high anti-bacterial efficiency, low side effects and its size is approximately 121 nm. BSA, as a nanocarrier, encapsulates the photosensitizer (E)-4-(4-(diphenylamino)styryl)-1-methylpyridin-1-ium with AIE properties named as BSA-Tpy, which increases its circulation time in vivo and improves the biocompatibility. Under acidic conditions (pH = 5.0), the surface positive charge of the BSA-Tpy is increased to +18.8 mV due to protonation of amine residues to achieve the targeting effect on bacteria. Besides, under the irradiation of white light, the BSA-Tpy will produce ROS to kill bacteria efficiently about 99.99% for both Gram-positive and Gram-negative bacteria, which shows the potential application value for the treatment of infected wounds. Conclusion: We have developed a feasible method for photodynamic antibacterial therapy, possessing excellent biocompatibility and high antibacterial efficiency with good fluorescence imaging property.

Application of nanosonosensitizer materials in cancer sono-dynamic therapy.

Sonodynamic therapy (SDT) is a novel non-invasive treatment for cancer combining low-intensity ultrasound and sonosensitizers. SDT activates sonosensitizers through ultrasound, releasing energy and generating reactive oxygen species to kill tumor cells. Compared with traditional photodynamic therapy (PDT), SDT is a promising anti-cancer therapy with the advantages of better targeting, deeper tissue penetration, and higher focusing ability. With the development and broad application of nanomaterials, novel sonosensitizers with tumor-targeting specificity can deliver to deep tumors and enhance the tumor microenvironment. In this review, we first review the mechanisms of sonodynamic therapy. In addition, we also focus on the current types of sonosensitizers and the latest design strategies of nanomaterials in sonosensitizers. Finally, we summarize the combined strategy of sonodynamic therapy.