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Infected diabetic wound (DW) presents a prolonged and challenging healing process within the field of regenerative medicine. The effectiveness of conventional drug therapies is hindered by their limited ability to reach deep tissues and promote adequate wound healing rates. Therefore, there is an imperative to develop drug delivery systems that can penetrate deep tissues while exhibiting multifunctional properties to expedite wound healing. In this study, w e devised a soluble microneedle (MN) patch made of γ‐PGA, featuring multiple arrays, which w as loaded with core‐shell structured nanoparticles (NPs) known as Ag@MSN@CeO2, to enhance the healing of infected DWs. The NP comprises a cerium dioxide (CeO2) core with anti‐inflammatory and antioxidant properties, a mesoporous silica NP (MSN) shell with angiogenic characteristics, and an outermost layer doped with Ag to combat bacterial infections. W e demonstrated that the MN platform loaded with Ag@MSN@CeO2successfully penetrated deep tissues for effective drug delivery. These MN tips induced the formation of multiple regenerative sites at various points, leading to antibacterial, reactive oxygen species‐lowering, macrophage ecological niche‐regulating, vascular regeneration‐promoting, and collagen deposition‐promoting effects, thus significantly expediting the healing process of infected DWs. Considering these findings, the multifunctional MN@Ag@MSN@CeO2patch exhibits substantial potential for clinical applications in the treatment of infected DW. A soluble microneedle patch made of γ‐PGA, loaded with core‐shell structured nanoparticles (Ag@MSN@CeO2), is developed to treat infected diabetic wounds. This patch effectively penetrates deep tissues, delivering antibacterial, anti‐inflammatory, and antioxidant properties while promoting vascular regeneration and collagen deposition, significantly enhancing wound healing. The multifunctional patch shows promise for clinical applications.

To investigate the protective effect of bexarotene in radiation-induced skin injury and elucidate underlying mechanism.

The potent immunomodulatory function of mesenchymal stem/stromal cells (MSCs) elicited by pro-inflammatory cytokines IFN-γ and TNF-α (IT) is critical to resolve inflammation and promote tissue repair. However, little is known about how the immunomodulatory capability of MSCs is related to their differentiation competency in the inflammatory microenvironment. In this study, we demonstrate that the adipocyte differentiation and immunomodulatory function of human adipose tissue derived MSCs (MSC(AD)s) are mutually exclusive. Mitochondrial reactive oxygen species (mtROS), which promote adipocyte differentiation, was decreased in MSC(AD)s due to IT-induced upregulation of superoxide dismutase 2 (SOD2). Furthermore, knockdown of SOD2 led to enhanced adipogenic differentiation but reduced immunosuppression capability of MSC(AD)s. Interestingly, the adipogenic differentiation was associated with increased mitochondrial biogenesis and upregulation of peroxisome proliferator- activated receptor-gamma coactivator-1apha (PPARGC1A/PGC-1α) expression. IT inhibited PGC-1α expression and decreased mitochondria mass but promoted glycolysis in an SOD2-dependent manner. Importantly, MSC(AD)s lacking SOD2 were compromised in their therapeutic efficacy in DSS-induced colitis in mice. Taken together, these findings indicate that the adipogenic differentiation and immunomodulation of MSC(AD)s may compete for resources in fulfilling the respective biosynthetic needs. Blocking of adipogenic differentiation by mitochondrial antioxidant may represent a novel strategy to enhance immunosuppressive activity of MSCs in inflammatory microenvironment.

Reconstruction of large scalp defects after tumor resection is common and challenging. Free skin grafting or free flap transfer is always performed. However, these techniques can result in poor functional and cosmetic outcomes.

Radiation-induced skin fibrosis is a detrimental and chronic disorder that occurs after radiation exposure. DNA methylation has been characterized as an important regulatory mechanism of multiple pathological processes. In this study, we compared the genome-wide DNA methylation status in radiation-induced fibrotic skin and adjacent normal tissues of rats by methylated DNA immunoprecipitation sequencing. Radiation-induced fibrotic skin showed differentially methylated regions associated with 3,650 protein-coding genes, 72 microRNAs, 5,836 long noncoding RNAs and 3 piwi-interacting RNAs. By integrating the mRNA and methylation profiles, the zinc transporter SLC39A9/ZIP9 was investigated in greater detail. The protein level of ZIP9 was increased in irradiated skin tissues of humans, monkeys, and rats, especially in radiogenic fibrotic skin tissues. Radiation induced the demethylation of a CpG dinucleotide in exon 1 of ZIP9that resulted in recruitment of the transcriptional factor Sp1 and increased ZIP9 expression. Overexpression of ZIP9 resulted in activation of the profibrotic transforming growth factor-β signaling pathway through protein kinase B in human fibroblasts. In addition, radiation-induced skin fibrosis was associated with increased zinc accumulation. The zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)-1,2-ethylenediamine abrogated ZIP9-induced activation of the transforming growth factor-β signaling pathway and attenuated radiation-induced skin fibrosis in a rat model. In summary, our findings illustrate epigenetic regulation of ZIP9 and its critical role in promoting radiation-induced skin fibrosis.