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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| Format: | Article |
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Nature Portfolio
2025-03-01
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| 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. |
| format | Article |
| id | doaj-art-8917f41da2c24a97bbc713a84f2a4005 |
| institution | DOAJ |
| issn | 2057-3995 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| 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 |
| work_keys_str_mv | AT arelirodriguezayala cellscaleporosityminimizesforeignbodyreactionandpromotesinnervatedmyofiberformationaftervolumetricmuscleloss AT georgechrist cellscaleporosityminimizesforeignbodyreactionandpromotesinnervatedmyofiberformationaftervolumetricmuscleloss AT donaldgriffin cellscaleporosityminimizesforeignbodyreactionandpromotesinnervatedmyofiberformationaftervolumetricmuscleloss |