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Repairing Volumetric Muscle Loss with Commercially Available Hydrogels in an Ovine Model.
Su, Eileen Y; Kennedy, Christopher S; Vega-Soto, Emmanuel E; Pallas, Brooke D; Lukpat, Samantha N; Hwang, Derek H; Bosek, David W; Forester, Celeste E; Loebel, Claudia; Larkin, Lisa M.
Afiliación
  • Su EY; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
  • Kennedy CS; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
  • Vega-Soto EE; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
  • Pallas BD; Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Lukpat SN; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, Michigan, USA.
  • Hwang DH; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
  • Bosek DW; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
  • Forester CE; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
  • Loebel C; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, Michigan, USA.
  • Larkin LM; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Tissue Eng Part A ; 30(9-10): 440-453, 2024 May.
Article en En | MEDLINE | ID: mdl-38117140
ABSTRACT
Volumetric muscle loss (VML) is the loss of skeletal muscle that exceeds the muscle's self-repair mechanism and leads to permanent functional deficits. In a previous study, we demonstrated the ability of our scaffold-free, multiphasic, tissue-engineered skeletal muscle units (SMUs) to restore muscle mass and force production. However, it was observed that the full recovery of muscle structure was inhibited due to increased fibrosis in the repair site. As such, novel biomaterials such as hydrogels (HGs) may have significant potential for decreasing the acute inflammation and subsequent fibrosis, as well as enhancing skeletal muscle regeneration following VML injury and repair. The goal of the current study was to assess the biocompatibility of commercially available poly(ethylene glycol), methacrylated gelatin, and hyaluronic acid (HA) HGs in combination with our SMUs to treat VML in a clinically relevant large animal model. An acute 30% VML injury created in the sheep peroneus tertius (PT) muscle was repaired with or without HGs and assessed for acute inflammation (incision swelling) and white blood cell counts in blood for 7 days. At the 7-day time point, HA was selected as the HG to use for the combined HG/SMU repair, as it exhibited a reduced inflammation response compared to the other HGs. Six weeks after implantation, all groups were assessed for gross and histological structural recovery. The results showed that the groups repaired with an SMU (SMU-Only and SMU+HA) restored muscle mass to greater degree than the groups with only HG and that the SMU groups had PT muscle masses that were statistically indistinguishable from its uninjured contralateral PT muscle. Furthermore, the HA HG, SMU-Only, and SMU+HA groups displayed notable efficacy in diminishing pro-inflammatory markers and showed an increased number of regenerating muscle fibers in the repair site. Taken together, the data demonstrates the efficacy of HA HG in decreasing acute inflammation and fibrotic response. The combination of HA and our SMUs also holds promise to decrease acute inflammation and fibrosis and increase muscle regeneration, advancing this combination therapy toward clinically relevant interventions for VML injuries in humans.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Músculo Esquelético / Hidrogeles Límite: Animals Idioma: En Revista: Tissue Eng Part A Asunto de la revista: BIOTECNOLOGIA / HISTOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Músculo Esquelético / Hidrogeles Límite: Animals Idioma: En Revista: Tissue Eng Part A Asunto de la revista: BIOTECNOLOGIA / HISTOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos