| Autor: |
Turner TC, Pittman FS, Zhang H, Hymel LA, Zheng T, Behara M, Anderson SE, Harrer JA, Link KA, Ahammed MA, Maner-Smith K, Liu X, Yin X, Lim HS, Spite M, Qiu P, García AJ, Mortensen LJ, Jang YC, Willett NJ, Botchwey EA |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 12. Date of Electronic Publication: 2024 Sep 12. |
| DOI: |
10.1101/2024.09.06.611741 |
| Abstrakt: |
Severe tissue loss resulting from extremity trauma, such as volumetric muscle loss (VML), poses significant clinical challenges for both general and military populations. VML disrupts the endogenous tissue repair mechanisms, resulting in acute and unresolved chronic inflammation and immune cell presence, impaired muscle healing, scar tissue formation, persistent pain, and permanent functional deficits. The aberrant healing response is preceded by acute inflammation and immune cell infiltration which does not resolve. We analyzed the biosynthesis of inflammatory and specialized pro-resolving lipid mediators (SPMs) after VML injury in two different models; muscle with critical-sized defects had a decreased capacity to biosynthesize SPMs, leading to dysregulated and persistent inflammation. We developed a modular poly(ethylene glycol)-maleimide hydrogel platform to locally release a stable isomer of Resolvin D1 (AT-RvD1) and promote endogenous pathways of inflammation resolution in the two muscle models. The local delivery of AT-RvD1 enhanced muscle regeneration, improved muscle function, and reduced pain sensitivity after VML by promoting molecular and cellular resolution of inflammation. These findings provide new insights into the pathogenesis of VML and establish a pro-resolving hydrogel therapeutic as a promising strategy for promoting functional muscle regeneration after traumatic injury. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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