Intramuscular Nanofat Injection Promotes Inflammation-Induced Gastrocnemius Regeneration in a Syngeneic Rat Sciatic Nerve Injury Model.


Journal

Plastic and reconstructive surgery
ISSN: 1529-4242
Titre abrégé: Plast Reconstr Surg
Pays: United States
ID NLM: 1306050

Informations de publication

Date de publication:
01 06 2023
Historique:
medline: 26 5 2023
pubmed: 3 2 2023
entrez: 2 2 2023
Statut: ppublish

Résumé

Mechanical emulsification of adipose tissue to concentrate protein and stromal cell components (ie, nanofat) has gained considerable interest in clinical practice. Although the regenerative potential of nanofat has largely been used in aesthetic applications, these effects have considerable potential in reconstruction as well. Here, the authors investigated the therapeutic properties of nanofat injected directly into the denervated gastrocnemius after a sciatic nerve injury in Lewis rats. Muscle denervation was induced by transecting and immediately repairing the sciatic nerve. Inguinal and subcutaneous adipose was harvested from donor rodents, processed into nanofat, and then injected intramuscularly into the gastrocnemius. Gait analysis was performed weekly. Rodents were euthanized at 9 and 12 weeks, after which tetanic contraction force was measured, and gene expression, histology, and cytokine multiplexing were performed. Intramuscular injection of nanofat significantly increased maximum tetanic force generation at 9 and 12 weeks. The forces of the nanofat-injected gastrocnemii were better correlated to their contralateral gastrocnemii relative to controls. Muscle repair-associated inflammatory gene expressions were significantly up-regulated in nanofat-injected gastrocnemii. Cytokines interleukin (IL)-1β, IL-18, vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, and tissue inhibitor of metalloproteinase-1 were significantly higher in nanofat-injected gastrocnemii relative to control gastrocnemii, and the tetanic force was linearly and significantly correlated to IL-1β and IL-18 and their interacting effects. Intramuscular injection of emulsified adipose tissue (nanofat) significantly increased gastrocnemii contraction force after sciatic nerve injury, with prolonged reconstructive inflammation by means of CD68, inducible nitric oxide synthase, IL-1β, and IL-18 all being potential mechanisms for this recovery. This application could potentially increase the therapeutic breadth of nanofat to include muscular recovery after nerve injury. The authors' study investigates a clinically translatable therapy to mitigate muscle atrophy after nerve injury.

Sections du résumé

BACKGROUND
Mechanical emulsification of adipose tissue to concentrate protein and stromal cell components (ie, nanofat) has gained considerable interest in clinical practice. Although the regenerative potential of nanofat has largely been used in aesthetic applications, these effects have considerable potential in reconstruction as well. Here, the authors investigated the therapeutic properties of nanofat injected directly into the denervated gastrocnemius after a sciatic nerve injury in Lewis rats.
METHODS
Muscle denervation was induced by transecting and immediately repairing the sciatic nerve. Inguinal and subcutaneous adipose was harvested from donor rodents, processed into nanofat, and then injected intramuscularly into the gastrocnemius. Gait analysis was performed weekly. Rodents were euthanized at 9 and 12 weeks, after which tetanic contraction force was measured, and gene expression, histology, and cytokine multiplexing were performed.
RESULTS
Intramuscular injection of nanofat significantly increased maximum tetanic force generation at 9 and 12 weeks. The forces of the nanofat-injected gastrocnemii were better correlated to their contralateral gastrocnemii relative to controls. Muscle repair-associated inflammatory gene expressions were significantly up-regulated in nanofat-injected gastrocnemii. Cytokines interleukin (IL)-1β, IL-18, vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, and tissue inhibitor of metalloproteinase-1 were significantly higher in nanofat-injected gastrocnemii relative to control gastrocnemii, and the tetanic force was linearly and significantly correlated to IL-1β and IL-18 and their interacting effects.
CONCLUSIONS
Intramuscular injection of emulsified adipose tissue (nanofat) significantly increased gastrocnemii contraction force after sciatic nerve injury, with prolonged reconstructive inflammation by means of CD68, inducible nitric oxide synthase, IL-1β, and IL-18 all being potential mechanisms for this recovery. This application could potentially increase the therapeutic breadth of nanofat to include muscular recovery after nerve injury.
CLINICAL RELEVANCE STATEMENT
The authors' study investigates a clinically translatable therapy to mitigate muscle atrophy after nerve injury.

Identifiants

pubmed: 36728782
doi: 10.1097/PRS.0000000000010115
pii: 00006534-202306000-00021
doi:

Substances chimiques

Interleukin-18 0
Tissue Inhibitor of Metalloproteinase-1 0
Vascular Endothelial Growth Factor A 0
Cytokines 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

947e-958e

Informations de copyright

Copyright © 2022 by the American Society of Plastic Surgeons.

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Auteurs

Benjamin K Schilling (BK)

From the Department of Bioengineering, School of Engineering.

Jocelyn S Baker (JS)

From the Department of Bioengineering, School of Engineering.

Chiaki Komatsu (C)

Department of Plastic Surgery, School of Medicine, University of Pittsburgh.

David M Turer (DM)

Department of Plastic Surgery, School of Medicine, University of Pittsburgh.

Fuat Baris Bengur (FB)

Department of Plastic Surgery, School of Medicine, University of Pittsburgh.

W Vincent Nerone (WV)

Department of Plastic Surgery, School of Medicine, University of Pittsburgh.

Feng Qin (F)

Department of Plastic Surgery, School of Medicine, University of Pittsburgh.

Adam R Cottrill (AR)

Department of Plastic Surgery, School of Medicine, University of Pittsburgh.

Lauren E Kokai (LE)

From the Department of Bioengineering, School of Engineering.
Department of Plastic Surgery, School of Medicine, University of Pittsburgh.
the McGowan Institute for Regenerative Medicine.

J Peter Rubin (JP)

From the Department of Bioengineering, School of Engineering.
Department of Plastic Surgery, School of Medicine, University of Pittsburgh.
the McGowan Institute for Regenerative Medicine.

Kacey G Marra (KG)

From the Department of Bioengineering, School of Engineering.
Department of Plastic Surgery, School of Medicine, University of Pittsburgh.
the McGowan Institute for Regenerative Medicine.

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