Abstract
Volumetric muscle loss (VML) overwhelms endogenous repair mechanisms, leading to defect contraction, fibrosis, and persistent aesthetic and functional deficits. Restorative biomaterials capable of re-establishing muscle structure and function represent promising strategies for treating severe injuries where conventional surgical repair is inadequate. Using a rat full-thickness VML model, we evaluated Oligomer, an engineered collagen polymeric biomaterial, in three prototype scaffold configurations that differed in application format and microstructure, with untreated defects serving as controls. Muscle structure, function, and tissue response were assessed longitudinally, including spatial transcriptomic profiling. Oligomer scaffolds supported regeneration of organized muscle architecture, including aligned myofibers, vascular networks, and integrated neurovascular structures. Higher-density scaffolds preserved defect geometry and yielded greater recovery of muscle mass and contractile function. Spatial transcriptomic analyses defined a regenerative remodeling mechanism distinct from reparative or constructive remodeling, characterized by an immunotolerant environment that enabled infiltration of diverse progenitor populations, including pro-regenerative mesenchymal cells, pericytes, satellite cells, and endothelial and neural stem cells. This cellular niche supported coordinated activation of myogenic, vascular, and neural pathways, recapitulating key aspects of developmental myogenesis. Collectively, these findings establish the mechanistic foundation for Oligomer scaffold-mediated regenerative remodeling and demonstrate its potential as a restorative biomaterial for treatment of VML.
Data availability
The spatial transcriptomics datasets generated in this study have been deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) under accession number GSE310073. All other data generated or analyzed in this study are available from the corresponding author upon reasonable request.
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Acknowledgements
The authors would like to thank the members of the Weldon School of Biomedical Engineering Preclinical Studies Team, including G. Brock, L. Carrell, and M. Bible. For histological analysis, we would like to acknowledge the assistance of the Purdue University Histology Research Laboratory, a core facility of the NIH-funded Indiana Clinical and Translational Science Institute. For transcriptomic analysis, we would like to thank the Center for Medical Genomics at the Indiana University School of Medicine, which is partially supported by the Indiana University Grand Challenges Precision Health Initiative.
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This research was funded by generous donations from the McKinley Family Foundation.
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R.A.M., J.S., L.Z., and S.V.-H. generated the concept and designed the study. R.A.M., J.S., L.Z., and E.D. conducted the experimental procedures. S.V.-H., R.A.M., J.S., E.D., and M.P. analyzed the data. H.G. and Y.L. assisted with the acquisition and interpretation of transcriptomic data. S.V.-H., S.H., and T.H.Q. provided project guidance and feedback. S.V.-H., R.A.M., J.S., and E.D. contributed to manuscript drafting, and all authors reviewed, provided comments, and edited the manuscript.
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S.V.-H. is the founder and a shareholder of GeniPhys, Inc. S.V.-H. does not hold an executive or operational role with the company. All other authors declare no competing interests.
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Morrison, R.A., Sexton, J., Zhang, L. et al. Immunotolerant Oligomer scaffolds promote regenerative remodeling and improved muscle structure and function after volumetric muscle loss. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42993-z
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DOI: https://doi.org/10.1038/s41598-026-42993-z
