C. Cai

Angiogenesis is a prominent component during the highly regulated process of wound healing. The application of exogenous vascular endothelial growth factor (VEGF) has shown considerable potential in facilitating angiogenesis. However, its effectiveness is often curtailed due to chronic inflammation and severe oxidative stress in diabetic wounds. Herein, an inflammation-responsive hydrogel incorporating Prussian blue nanoparticles (PBNPs) is designed to augment the angiogenic efficacy of VEGF. Specifically, the rapid release of PBNPs from the hydrogel under inflammatory conditions effectively alleviates the oxidative stress of the wound, therefore reprogramming the immune microenvironment to preserve the bioactivity of VEGF for enhanced angiogenesis. In vitro and in vivo studies reveal that the PBNPs and VEGF co-loaded hydrogel is biocompatible and possesses effective anti-inflammatory properties, thereby facilitating angiogenesis to accelerate the wound healing process in a type 2 diabetic mouse model.

Wound infections are one of the major threats to human health, accounting for millions of deaths annually. Real-time monitoring, accurate diagnosis, and on-demand therapy are crucial to minimizing complications and saving lives. Herein, we propose a “monitor-and-treat” strategy for infected wound management by integrating the emerging development of bacterio-therapeutics and bio-optics. The upper layer consists of gelatin methacryloyl (GelMA)-collagen III methacryloyl (Col 3 MA) (GC), Reuterin (Reu) isolated from the probiotic Lactobacillus reuteri (L. reuteri) and microfluidic safflower polysaccharide (SPS)@GelMA microspheres using 3D printing technology. The lower layer is made of acryloylated glycine (ACG) hydrogel with tissue adhesion capability, which enables the hydrogel to adapt to the movement and stretching of the skin. By integrating temperature-sensitive polydimethylsiloxane (PDMS) optical fibers, the ACG-GC/Reu/SPS-PDMS hydrogel could accurately and steadily sense and send wound temperature information to intelligent devices for real-time monitoring of the healing status (“monitor”). The double-layered hydrogel not only inhibited bacterial survival and colonization (97.4 % against E. coli and 99 % against S. aureus ), but also exhibited remarkable hemostatic properties. Furthermore, it was conducive to L929 cell proliferation and pro-angiogenesis, and promoted the polarization of pro‐inflammatory M1 macrophages to the anti‐inflammatory M2‐phenotype, therefore creating a favorable immune microenvironment at the wound site. Animal experiments using SD rats and Bama minipigs demonstrated that this hydrogel promoted wound closure, directed polarization to M2 macrophages, alleviated inflammation, enhanced neovascularization, therefore accelerating infected wound healing (“treat”). In addition, RNA-Seq analysis revealed the mechanism of action of ACG-GC/Reu/SPS-PDMS hydrogel in modulating key signaling pathways, including down-regulation of AMPK, IL-17, and NF-κB signaling pathways, activation of NLRP3 inflammatory vesicles, and enrichment of MAPK, TGF-β, PI3K-Akt, TNF, and VEGF signaling pathways. The modulation of these signaling pathways suggests that hydrogels play an important role in the molecular mechanisms that promote wound healing and tissue regeneration. Therefore, the design of this study provides an innovative and multifunctional bandage strategy that can significantly improve pathologic diagnosis and wound treatment. • Real-time monitoring and on-demand treatment are combined to achieve the purpose of “monitoring and treatment”. • Dual-layer hydrogel with antibacterial, hemostatic and adhesive properties. • Temperature sensitive PDMS fiber optics for continuous monitoring of wound status. • Promote macrophage polarization, reduce inflammatory response and support tissue repair. • ACG-GC/Reu/SPS-PDMS hydrogel accelerates wound healing, enhances neovascularization and improves immune response.

1. This study explored the tissue metabolic status and the relationship with inflammation in valgus-valgus deformity (VVD) broilers with increasing age.2. Tissue and blood from VVD and healthy broilers were collected at two, four and five weeks old. A fully automated biochemical analyser, real-time PCR, HE staining and enzyme-linked immunosorbent assay were used to detect tissue metabolic indexes, mRNA levels of inflammation and apoptosis cytokines in immune organs, histological changes and serum inflammation and immune-related protein contents in VVD broilers.3. The results showed that VVD increased the levels of total protein, albumin, alanine aminotransferase at five weeks of age, aspartate aminotransferase, urea and creatine kinase in blood at two weeks of age. It upregulated the gene expression of inflammatory factors IL-1β, IL-6, IL-8, TNF-α, NF-κB and TGF-β and apoptotic factors FAS, Bcl-2, caspase-3 and 9 in immune organs; increased levels of serum proteins TNF-α, IL-1β and IL-6 and decreased levels of serum immunoglobulins IgY and CD3+.4. In addition, with increasing age, IL-10 gene expression gradually increased in the BF and decreased in the spleen.5. In conclusion, VVD broilers have disorders of liver and kidney metabolism, inflammation and apoptosis of immune organs and increased levels of serum inflammatory factor proteins.

expression.5. This study systematically investigated overall DNA methylation patterns in the leg muscle of VVD and normal broilers. It screened common differential genes in conjunction with transcriptomic data to further identify genes associated with muscle growth and development. This study provides new insights to better understand the pathogenesis of VVD from an epigenetic perspective.