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Advanced Science

IF: 14.3
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Programmed BRD9 Degradation and Hedgehog Signaling Activation via Silk-Based Core-Shell Microneedles Promote Diabetic Wound Healing

Published:16 October 2024 DOI: 10.1002/advs.202404130 PMID: 39413023
Yili Liu, Mingliang Zhou, Jinrui Sun, Enhui Yao, Jingyi Xu, Guangzheng Yang, Xiaolin Wu, Ling Xu, Jiahui Du, Xinquan Jiang

Abstract

Wound healing impairment in diabetes mellitus is associated with an excessive inflammatory response and defective regeneration capability with suppressed Hedgehog (Hh) signaling. The bromodomain protein BRD9, a subunit of the non-canonical BAF chromatin-remodeling complex, is critical for macrophage inflammatory response. However, whether the epigenetic drug BRD9 degrader can attenuate the sustained inflammatory state of wounds in diabetes remains unclear. Without a bona fide immune microenvironment, Hh signaling activation fails to effectively rescue the suppressed proliferative ability of dermal fibroblasts and the vascularization of endothelial cells. Therefore, a silk-based core-shell microneedle (MN) patch is proposed to dynamically modulate the wound immune microenvironment and the regeneration process. Specifically, the BRD9 degrader released from the shell of the MNs mitigated the excessive inflammatory response in the early phase. Subsequently, the positively charged Hh signaling agonist is released from the negatively charged core of the silk fibroin nanofibers and promotes the phase transition from inflammation to regeneration, including re-epithelialization, collagen deposition, and angiogenesis. These findings suggest that the programmed silk-based core-shell MN patch is an ideal therapeutic strategy for effective skin regeneration in diabetic wounds.

Substances (12)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Rhodamine 6G 989-38-8 C28H31ClN2O3 420 suppliers $10.00-$638.00
Rhodamine 6G 989-38-8 C28H31ClN2O3 420 suppliers $10.00-$638.00
Rhodamine 6G 989-38-8 C28H31ClN2O3 420 suppliers $10.00-$638.00
Rhodamine 6G 989-38-8 C28H31ClN2O3 420 suppliers $10.00-$638.00
SAG 912545-86-9 C28H28ClN3OS 158 suppliers $29.00-$2500.00
SAG 912545-86-9 C28H28ClN3OS 158 suppliers $29.00-$2500.00
SAG 912545-86-9 C28H28ClN3OS 158 suppliers $29.00-$2500.00
SAG 912545-86-9 C28H28ClN3OS 158 suppliers $29.00-$2500.00
dBRD9 2170679-45-3 C40H45N7O10 44 suppliers Inquiry
dBRD9 2170679-45-3 C40H45N7O10 44 suppliers Inquiry

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