Cell-scale porosity minimizes foreign body reaction and promotes innervated myofiber formation after volumetric muscle loss

Abstract Volumetric muscle loss (VML) from severe traumatic injuries results in irreversible loss of contractile tissue and permanent functional deficits. These injuries resist endogenous healing and clinical treatment due to excessive inflammation, leading to fibrosis, muscle fiber denervation, and...

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Main Authors: Areli Rodriguez Ayala, George Christ, Donald Griffin
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:npj Regenerative Medicine
Online Access:https://doi.org/10.1038/s41536-025-00395-1
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author Areli Rodriguez Ayala
George Christ
Donald Griffin
author_facet Areli Rodriguez Ayala
George Christ
Donald Griffin
author_sort Areli Rodriguez Ayala
collection DOAJ
description Abstract Volumetric muscle loss (VML) from severe traumatic injuries results in irreversible loss of contractile tissue and permanent functional deficits. These injuries resist endogenous healing and clinical treatment due to excessive inflammation, leading to fibrosis, muscle fiber denervation, and impaired regeneration. Using a rodent tibialis anterior VML model, this study demonstrates microporous annealed particle (MAP) hydrogel scaffolds as a biomaterial platform for improved muscle regeneration. Unlike bulk (nanoporous) hydrogel scaffolds, MAP scaffolds enhance integration by preventing a foreign body reaction, slowing implant degradation, and promoting regenerative macrophage polarization. Cell migration and angiogenesis occur throughout the implant before MAP scaffold degradation, with muscle fibers and neuromuscular junctions forming within the scaffolds. These structures continue developing as the implant degrades, suggesting MAP hydrogel scaffolds offer a promising therapeutic approach for VML injuries.
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series npj Regenerative Medicine
spelling doaj-art-8917f41da2c24a97bbc713a84f2a40052025-08-20T03:00:37ZengNature Portfolionpj Regenerative Medicine2057-39952025-03-0110111610.1038/s41536-025-00395-1Cell-scale porosity minimizes foreign body reaction and promotes innervated myofiber formation after volumetric muscle lossAreli Rodriguez Ayala0George Christ1Donald Griffin2Department of Biomedical Engineering, University of VirginiaDepartment of Biomedical Engineering, University of VirginiaDepartment of Biomedical Engineering, University of VirginiaAbstract Volumetric muscle loss (VML) from severe traumatic injuries results in irreversible loss of contractile tissue and permanent functional deficits. These injuries resist endogenous healing and clinical treatment due to excessive inflammation, leading to fibrosis, muscle fiber denervation, and impaired regeneration. Using a rodent tibialis anterior VML model, this study demonstrates microporous annealed particle (MAP) hydrogel scaffolds as a biomaterial platform for improved muscle regeneration. Unlike bulk (nanoporous) hydrogel scaffolds, MAP scaffolds enhance integration by preventing a foreign body reaction, slowing implant degradation, and promoting regenerative macrophage polarization. Cell migration and angiogenesis occur throughout the implant before MAP scaffold degradation, with muscle fibers and neuromuscular junctions forming within the scaffolds. These structures continue developing as the implant degrades, suggesting MAP hydrogel scaffolds offer a promising therapeutic approach for VML injuries.https://doi.org/10.1038/s41536-025-00395-1
spellingShingle Areli Rodriguez Ayala
George Christ
Donald Griffin
Cell-scale porosity minimizes foreign body reaction and promotes innervated myofiber formation after volumetric muscle loss
npj Regenerative Medicine
title Cell-scale porosity minimizes foreign body reaction and promotes innervated myofiber formation after volumetric muscle loss
title_full Cell-scale porosity minimizes foreign body reaction and promotes innervated myofiber formation after volumetric muscle loss
title_fullStr Cell-scale porosity minimizes foreign body reaction and promotes innervated myofiber formation after volumetric muscle loss
title_full_unstemmed Cell-scale porosity minimizes foreign body reaction and promotes innervated myofiber formation after volumetric muscle loss
title_short Cell-scale porosity minimizes foreign body reaction and promotes innervated myofiber formation after volumetric muscle loss
title_sort cell scale porosity minimizes foreign body reaction and promotes innervated myofiber formation after volumetric muscle loss
url https://doi.org/10.1038/s41536-025-00395-1
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AT georgechrist cellscaleporosityminimizesforeignbodyreactionandpromotesinnervatedmyofiberformationaftervolumetricmuscleloss
AT donaldgriffin cellscaleporosityminimizesforeignbodyreactionandpromotesinnervatedmyofiberformationaftervolumetricmuscleloss