McFaline-Figueroa Jennifer, Raymond-Pope Christiana J, Pearson Joseph J, Schifino Albino G, Heo Junwon, Lillquist Thomas J, Pritchard Emma E, Winders Elizabeth A, Hunda Edward T, Temenoff Johnna S, Greising Sarah M, Call Jarrod A
Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA.
School of Kinesiology, University of Minnesota, Minneapolis, MN 55455, USA.
Regen Biomater. 2025 Mar 19;12:rbaf015. doi: 10.1093/rb/rbaf015. eCollection 2025.
Volumetric muscle loss (VML) injury results in the unrecoverable loss of muscle mass and contractility. Oral delivery of formoterol, a β-adrenergic receptor agonist, produces a modest recovery of muscle mass and contractility in VML-injured mice. The objective of this study was to determine if a regenerative rehabilitation paradigm or a regenerative medicine paradigm could enhance the recovery of VML-injured muscle. Regenerative rehabilitation involved oral formoterol delivery combined with voluntary wheel running. Regenerative medicine involved direct delivery of formoterol to VML-injured muscle using a non-biodegradable poly(ethylene glycol) biomaterial. To determine if the regenerative rehabilitation or regenerative medicine approaches were effective at 8 weeks post-injury, muscle mass, contractile function, metabolic function, and histological evaluations were used. One model of regenerative rehabilitation, in which rehabilitation was delayed until 1 month post-injury, resulted in greater muscle mass, muscle contractility, and permeabilized muscle fiber mitochondrial respiration compared to untreated VML-injured mice. Histologically, these mice had evidence of greater total muscle fiber number and oxidative fibers; however, they also had a greater percentage of densely packed collagen. The regenerative medicine model produced greater permeabilized muscle fiber mitochondrial respiration compared to untreated VML-injured mice; however, the non-biodegradable biomaterial was associated with fewer total muscle fibers and lower muscle quality (i.e. lower muscle mass-normalized contractility). The conclusions reached from this study are: (i) regenerative rehabilitation and regenerative medicine strategies utilizing formoterol require further optimization but showed promising outcomes; and (ii) in general, β-adrenergic receptor agonism continues to be a physiologically supportive intervention to improve muscle contractile and metabolic function after VML injury.
容积性肌肉损失（VML）损伤会导致肌肉质量和收缩力不可恢复的损失。口服β-肾上腺素能受体激动剂福莫特罗可使VML损伤小鼠的肌肉质量和收缩力得到一定程度的恢复。本研究的目的是确定再生康复模式或再生医学模式是否能增强VML损伤肌肉的恢复。再生康复包括口服福莫特罗并结合自愿轮转跑步。再生医学则是使用不可生物降解的聚乙二醇生物材料将福莫特罗直接递送至VML损伤的肌肉。为了确定再生康复或再生医学方法在损伤后8周是否有效，采用了肌肉质量、收缩功能、代谢功能和组织学评估。一种再生康复模型，其中康复延迟至损伤后1个月，与未治疗的VML损伤小鼠相比，该模型导致更大的肌肉质量、肌肉收缩力以及通透性肌肉纤维线粒体呼吸。组织学上，这些小鼠有更多的总肌纤维数量和氧化纤维的证据；然而，它们也有更高比例的致密堆积胶原蛋白。与未治疗的VML损伤小鼠相比，再生医学模型产生了更大的通透性肌肉纤维线粒体呼吸；然而，不可生物降解的生物材料与更少的总肌纤维和更低的肌肉质量（即更低的肌肉质量标准化收缩力）相关。本研究得出的结论是：（i）利用福莫特罗的再生康复和再生医学策略需要进一步优化，但显示出有前景的结果；（ii）一般来说，β-肾上腺素能受体激动仍然是一种生理支持性干预措施，可改善VML损伤后肌肉的收缩和代谢功能。
Zotero 插件
