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Oral delivery of formoterol, a \u03b22-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, \u03b2-adrenergic receptor agonism continues to be a physiologically supportive intervention to improve muscle contractile and metabolic function after VML injury.<\/jats:p>","DOI":"10.1093\/rb\/rbaf015","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T04:13:21Z","timestamp":1742444001000},"source":"Crossref","is-referenced-by-count":9,"title":["Advancing \u03b2-adrenoreceptor agonism for recovery after volumetric muscle loss through regenerative rehabilitation and biomaterial delivery approaches"],"prefix":"10.1093","volume":"12","author":[{"given":"Jennifer","family":"McFaline-Figueroa","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Georgia , Athens, GA 30602,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana J","family":"Raymond-Pope","sequence":"additional","affiliation":[{"name":"School of Kinesiology, University of Minnesota , Minneapolis, MN 55455,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J","family":"Pearson","sequence":"additional","affiliation":[{"name":"W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University , Atlanta, GA 30032,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albino G","family":"Schifino","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Georgia , Athens, GA 30602,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwon","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Georgia , Athens, GA 30602,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J","family":"Lillquist","sequence":"additional","affiliation":[{"name":"School of Kinesiology, University of Minnesota , Minneapolis, MN 55455,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma E","family":"Pritchard","sequence":"additional","affiliation":[{"name":"School of Kinesiology, University of Minnesota , Minneapolis, MN 55455,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A","family":"Winders","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Georgia , Athens, GA 30602,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward T","family":"Hunda","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Georgia , Athens, GA 30602,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnna S","family":"Temenoff","sequence":"additional","affiliation":[{"name":"W.H. 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