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Transcriptomic profiling of diabetic wound tissues treated with multifunctional microneedles integrating spermidine- and TGF-β3-regulated dental pulp stem cell spheroids

ABSTRACT: Diabetic chronic wounds exhibit impaired tissue repair characterized by persistent inflammation, oxidative stress, defective extracellular matrix remodeling, and insufficient regeneration. In this study, RNA sequencing was performed to investigate transcriptomic changes in diabetic wound tissues following treatment with multifunctional microneedles (DST-MNs) integrating spermidine- and TGF-β3-regulated dental pulp stem cell spheroids. Full-thickness diabetic wounds were established in rats, and wound tissues from untreated diabetic wound animals and DST-MNs-treated animals were collected for transcriptome profiling. Differentially expressed genes and enriched biological pathways were analyzed to identify molecular mechanisms associated with DST-MNs-mediated wound repair. These data provide insights into transcriptional regulation involved in inflammatory modulation, extracellular matrix remodeling, angiogenesis, and diabetic wound regeneration.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE342853 | GEO | 2026/08/11

REPOSITORIES: GEO

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Project description:Diabetic wounds require continuous and coordinated modulation of the microenvironment concurrent with tissue regeneration, yet this remains a significant challenge. As a proof of concept, we herein propose to use dimeric copper peptide for diabetic wound treatment. The dimeric copper peptide (D-CuP) was first synthesized and then incorporated into a reactive oxygen species (ROS)-responsive hydrogel matrix to improve therapeutic compliance, culminating in the formulation of G/D-CuP. Compared to monomer copper peptide (CuP), a wound healing agent, D-CuP exhibits multivalency, enhanced biologic stability against proteases and the broad biological activities, such as anti-inflammatory and antioxidative properties, while promoting angiogenesis and fibroblast proliferation and migration. Meanwhile, the hydrogel matrix, exhibiting excellent ROS-scavenging capabilities, has been engineered to an intelligent drug reservoir for wound-responsive release of D-CuP at the wound site while simultaneously attenuating inflammatory responses. Ultimately, the G/D-CuP group demonstrated superior therapeutic efficacy, achieving in 97.2% closure of infected wounds.In this study, we present a proof-of-concept study to optimize the treatment of diabetic wounds. This method integrates a dimeric copper peptide hydrogel (G/D-CuP) to address several critical factors: i) The design and synthesis of the dimeric copper peptide (D-CuP) feature a broad range of targets and enhanced biological activities, such as anti-inflammatory and antioxidative properties, while promoting angiogenesis and fibroblast proliferation and migration; ii) Utilizing the steric hindrance conferred by dimerization reduces protease access to the active site and significantly improving stability against proteases; iii) A ROS-responsive hydrogel matrix has been synthesized, exhibiting superior ROS-scavenging capabilities, functioning as an intelligent drug reservoir that enables the controlled release of D-CuP at the wound interface while simultaneously attenuating inflammatory responses in the microenvironment; iv) G/D-CuP possesses outstanding deformability and spreadability, allowing it to adapt to any wound shape; v) The synthesis and preparation process of G/D-CuP are straightforward and cost-effective, making it highly promising for clinical translation. This multifunctional treatment platform is anticipated to accommodate the complex and dynamic biological processes involved in diabetic wound healing, thereby significantly improving the overall efficacy of wound healing treatments.

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Transcriptomic profiling of diabetic wound tissues treated with multifunctional microneedles integrating spermidine- and TGF-β3-regulated dental pulp stem cell spheroids

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