Separable Microneedles with Photosynthesis-Driven Oxygen Manufactory for Diabetic Wound Healing.

Oxygen plays an important role in diabetic chronic wound healing by regulating various life activities such as cell proliferation, migration, and angiogenesis. Therefore, oxygen-delivering systems have drawn much attention and evolved continuously. Here, we propose that an active Chlorella vulgaris (Cv)-loaded separable microneedle (MN) can be used to control oxygen delivery, which then promotes wound healing. The Cv-loaded microneedles (CvMN) consist of a polyvinyl acetate (PVA) substrate and gelatin methacryloyl (GelMA) tips with encapsulated Cv. Once CvMN is applied to diabetic wound, the PVA basal layer is rapidly dissolved in a short time, while the noncytotoxic and biocompatible GelMA tips remain in the skin. By taking advantage of the photosynthesis of Cv, oxygen would be continuously produced in a green way and released from CvMN in a controlled manner. Both in vitro and in vivo results showed that CvMN could promote cell proliferation, migration, and angiogenesis and enhance wound healing in diabetic mice effectively. The remarkable therapeutic effect is mainly attributed to the continuous generation of dissolved oxygen in CvMN and the presence of antioxidant vitamins, γ-linolenic acid, and linoleic acid in Cv. Thus, CvMN provides a promising strategy for diabetic wound healing with more possibility of clinical transformations.

Therapeutic exosomal vaccine for enhanced cancer immunotherapy by mediating tumor microenvironment.

Tumor immunotherapy has been convincingly demonstrated as a feasible approach for treating cancers. Although promising, the immunosuppressive tumor microenvironment (TME) has been recognized as a major obstacle in tumor immunotherapy. It is highly desirable to release an immunosuppressive "brake" for improving cancer immunotherapy. Among tumor-infiltrated immune cells, tumor-associated macrophages (TAMs) play an important role in the growth, invasion, and metastasis of tumors. The polarization of TAMs (M2) into the M1 type can alleviate the immunosuppression of the TME and enhance the effect of immunotherapy. Inspired by this, we constructed a therapeutic exosomal vaccine from antigen-stimulated M1-type macrophages (M1OVA-Exos). M1OVA-Exos are capable of polarizing TAMs into M1 type through downregulation of the Wnt signaling pathway. Mediating the TME further activates the immune response and inhibits tumor growth and metastasis via the exosomal vaccine. Our study provides a new strategy for the polarization of TAMs, which augments cancer vaccine therapy efficacy.

Engineering a photosynthetic bacteria-incorporated hydrogel for infected wound healing.

Treating wounds with multidrug-resistant bacterial infections remains a huge and arduous challenge. In this work, we prepared a "live-drug"-encapsulated hydrogel dressing for the treatment of multidrug-resistant bacterial infections and full-thickness skin incision repair. Our live dressing was comprised of photosynthetic bacteria (PSB) and extracellular matrix (ECM) gel with photothermal, antibacterial and antioxidant properties, as well as good cytocompatibility and blood compatibility. More interestingly, live PSB could be regarded as not only photothermal agents but also as anti-inflammatory agents to promote wound healing owing to their antioxidant metabolites. In vitro and in vivo studies showed that the PSB hydrogel not only had a high killing rate against methicillin-resistant Staphylococcus aureus (MRSA) but it also accelerated collagen deposition and granulation tissue formation by promoting cell proliferation and migration, which significantly promoted skin tissue regeneration and wound healing. We believe that the large-scale production of PSB Gel-based therapeutic dressings has the advantages of easy use and promising clinical applications. STATEMENT OF SIGNIFICANCE: Rapid wound healing and the treatment of bacterial infections have always been the two biggest challenges in the field of wound care. We prepared a "live drug" dressing by encapsulating photosynthetic bacteria into an extracellular matrix hydrogel to sterilize the wound and promote wound healing. First, photosynthetic bacteria are not only a photothermal agent for photothermal wound sterilization, but also possess the anti-inflammatory capacity to enhance wound healing due to their antioxidant metabolites. Second, the extracellular matrix hydrogel is rich in a variety of growth factors and nutrients to promote cell migration and accelerate wound healing. Third, photosynthetic bacteria are not only green and non-toxic, but also can be obtained on a large scale, which facilitates manufacturing and clinical transformation.