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The inflammasome is a multiprotein complex critical for the innate immune response to injury. Inflammasome activation initiates healthy wound healing, but comorbidities with poor healing, including diabetes, exhibit pathologic, sustained activation with delayed resolution that prevents healing progression. In prior work, we reported the allosteric P2X7 antagonist A438079 inhibits extracellular ATP-evoked NLRP3 signaling by preventing ion flux, mitochondrial reactive oxygen species generation, NLRP3 assembly, mature IL-1β release, and pyroptosis. However, the short half-lifein vivolimits clinical translation of this promising molecule. Here, we develop a controlled release scaffold to deliver A438079 as an inflammasome-modulating wound dressing for applications in poorly healing wounds. We fabricated and characterized tunable thickness, long-lasting silk fibroin dressings and evaluated A438079 loading and release kinetics. We characterized A438079-loaded silk dressingsin vitroby measuring IL-1β release and inflammasome assembly by perinuclear ASC speck formation. We further evaluated the performance of A438079-loaded silk dressings in a full-thickness model of wound healing in genetically diabetic mice and observed acceleration of wound closure by 10 days post-wounding with reduced levels of IL-1β at the wound edge. This work provides a proof-of-principle for translating pharmacologic inhibition of ATP-induced inflammation in diabetic wounds and represents a novel approach to therapeutically targeting a dysregulated mechanism in diabetic wound impairment.
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This content will become publicly available on June 1, 2026
Oxytocin impairs wound-healing during social isolation but not social living
Social isolation hampers immune system function, and the biological mechanisms driving this effect remain understudied. We hypothesized that oxytocin (OT), a key neuropeptide involved in social cognition, is a critical mediator of social context on immune function. In the California mouse (Peromyscus californicus), we examined how female and male immune function is influenced by (1) social isolation from same-sex peers, (2) social peer affiliation, and (3) exogenous OT. We evaluated immune function through wound size progression following a skin biopsy and proinflammatory cytokines in the wound fluid. Unexpectedly, social isolation alone did not influence wound healing, but isolation +OT increased wound size in a dose dependent manner. Wound size progression interacted with sex and OT in socially-housed mice, suggesting that OT increases inflammation in females, while decreasing inflammation in males in a social context-dependent manner. Inflammatory biomarker interleukin-6 (IL-6) mRNA expression correlated with wound size overall, supporting wound healing as an index of inflammatory response. However, isolation +OT mice did not have higher levels of IL-6, suggesting that the mechanism through which isolation +OT influences wound size is not through IL-6 activity. Behaviorally, higher levels of affiliation were negatively associated with wound size, and this effect was diminished by OT treatment. Our results highlight that the anti-inflammatory effects of OT are likely highly dependent on social context.
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- Award ID(s):
- 1946613
- PAR ID:
- 10582408
- Publisher / Repository:
- Elsevier
- Date Published:
- Journal Name:
- Psychoneuroendocrinology
- Volume:
- 176
- Issue:
- C
- ISSN:
- 0306-4530
- Page Range / eLocation ID:
- 107445
- Subject(s) / Keyword(s):
- oxytocin, social bond, isolation, inflammation, wound healing, affiliation
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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