Bioinstructive scaffolds enhance stem cell engraftment for functional tissue regeneration
Source abstract
Abstract
Stem cell therapy is a promising approach for tissue regeneration after traumatic injury, yet current applications are limited by inadequate control over the fate of stem cells after transplantation. Here we introduce a bioconstruct engineered for the staged release of growth factors, tailored to direct different phases of muscle regeneration. The bioconstruct is composed of a decellularized extracellular matrix containing polymeric nanocapsules sequentially releasing basic fibroblast growth factor and insulin-like growth factor 1, which promote the proliferation and differentiation of muscle stem cells, respectively. When applied to a volumetric muscle loss defect in an animal model, the bioconstruct enhances myofibre formation, angiogenesis, innervation and functional restoration. Further, it promotes functional muscle formation with human or aged murine muscle stem cells, highlighting the translational potential of this bioconstruct. Overall, these results highlight the potential of bioconstructs with orchestrated growth factor release for stem cell therapies in traumatic injury.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Electrospun Nanofibers in Biomedical Applications · 3D Printing in Biomedical Research · Silk-based biomaterials and applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (54)
Show source-provided references
1. Discher, D. E., Mooney, D. J. & Zandstra, P. W. Growth factors, matrices, and forces combine and control stem cells. Science 324, 1673–1677 (2009).10.1126/science.1171643 ↗
2. Lepper, C., Partridge, T. A. & Fan, C.-M. An absolute requirement for Pax7-positive satellite cells in acute injury-induced skeletal muscle regeneration. Development 138, 3639–3646 (2011).10.1242/dev.067595 ↗
3. Sambasivan, R. et al. Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration. Development 138, 3647–3656 (2011).10.1242/dev.067587 ↗
4. Wosczyna, M. N. & Rando, T. A. A muscle stem cell support group: coordinated cellular responses in muscle regeneration. Dev. Cell 46, 135–143 (2018).10.1016/j.devcel.2018.06.018 ↗
5. Eugenis, I., Wu, D. & Rando, T. A. Cells, scaffolds, and bioactive factors: engineering strategies for improving regeneration following volumetric muscle loss. Biomaterials 278, 121173 (2021).10.1016/j.biomaterials.2021.121173 ↗
6. Mitrousis, N., Fokina, A. & Shoichet, M. S. Biomaterials for cell transplantation. Nat. Rev. Mater. 3, 174–195 (2018).10.1038/s41578-018-0057-0 ↗
7. Kharbikar, B. N., Mohindra, P. & Desai, T. A. Biomaterials to enhance stem cell transplantation. Cell Stem Cell 29, 692–721 (2022).10.1016/j.stem.2022.04.002 ↗
8. Quarta, M. et al. Bioengineered constructs combined with exercise enhance stem cell-mediated treatment of volumetric muscle loss. Nat. Commun. 8, 15613 (2017).10.1038/ncomms15613 ↗
9. Syverud, B. C., VanDusen, K. W. & Larkin, L. M. Growth factors for skeletal muscle tissue engineering. Cells Tissues Organs 202, 169–179 (2016).10.1159/000444671 ↗
10. Lee, K., Silva, E. A. & Mooney, D. J. Growth factor delivery-based tissue engineering: general approaches and a review of recent developments. J. R. Soc. Interface 8, 153–170 (2011).10.1098/rsif.2010.0223 ↗
11. Li, J. & Mooney, D. J. Designing hydrogels for controlled drug delivery. Nat. Rev. Mater. 1, 16071 (2016).10.1038/natrevmats.2016.71 ↗
12. Richardson, T. P., Peters, M. C., Ennett, A. B. & Mooney, D. J. Polymeric system for dual growth factor delivery. Nat. Biotechnol. 19, 1029–1034 (2001).10.1038/nbt1101-1029 ↗
13. Pakulska, M. M. et al. Encapsulation-free controlled release: electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles. Sci. Adv. 2, e1600519 (2016).10.1126/sciadv.1600519 ↗
14. Gaharwar, A. K., Singh, I. & Khademhosseini, A. Engineered biomaterials for in situ tissue regeneration. Nat. Rev. Mater. https://doi.org/10.1038/s41578-020-0209-x (2020).10.1038/s41578-020-0209-x ↗
15. Pawlikowski, B., Vogler, T. O., Gadek, K. & Olwin, B. B. Regulation of skeletal muscle stem cells by fibroblast growth factors. Dev. Dyn. 246, 359–367 (2017).10.1002/dvdy.24495 ↗
16. Yoshida, T. & Delafontaine, P. Mechanisms of IGF-1-mediated regulation of skeletal muscle hypertrophy and atrophy. Cells 9, 1970 (2020).10.3390/cells9091970 ↗
17. Greising, S. M., Corona, B. T., McGann, C., Frankum, J. K. & Warren, G. L. Therapeutic approaches for volumetric muscle loss injury: a systematic review and meta-analysis. Tissue Eng. Part B Rev. 25, 510–525 (2019).10.1089/ten.teb.2019.0207 ↗
18. Hu, C. et al. A mouse model of volumetric muscle loss and therapeutic scaffold implantation. Nat. Protoc. https://doi.org/10.1038/s41596-024-01059-y (2024).10.1038/s41596-024-01059-y ↗
19. Xiao, W. et al. Time-dependent gene expression analysis after mouse skeletal muscle contusion. J. Sport Health Sci. 5, 101–108 (2016).10.1016/j.jshs.2016.01.017 ↗
20. Mehiri, S. N. et al. Time-based gene expression programme following diaphragm injury in a rat model. Eur. Respir. J. 25, 422–430 (2005).10.1183/09031936.05.00047704 ↗
21. Cezar, C. A. & Mooney, D. J. Biomaterial-based delivery for skeletal muscle repair. Adv. Drug Deliv. Rev. 84, 188–197 (2015).10.1016/j.addr.2014.09.008 ↗
22. Qazi, T. H., Mooney, D. J., Pumberger, M., Geissler, S. & Duda, G. N. Biomaterials based strategies for skeletal muscle tissue engineering: existing technologies and future trends. Biomaterials 53, 502–521 (2015).10.1016/j.biomaterials.2015.02.110 ↗
23. Larouche, J., Greising, S. M., Corona, B. T. & Aguilar, C. A. Robust inflammatory and fibrotic signaling following volumetric muscle loss: a barrier to muscle regeneration. Cell Death Dis. 9, 409 (2018).10.1038/s41419-018-0455-7 ↗
24. Hurtgen, B. J. et al. Severe muscle trauma triggers heightened and prolonged local musculoskeletal inflammation and impairs adjacent tibia fracture healing. J. Musculoskelet. Neuronal Interact. 16, 122–134 (2016).
25. Corona, B. T. et al. The promotion of a functional fibrosis in skeletal muscle with volumetric muscle loss injury following the transplantation of muscle-ECM. Biomaterials 34, 3324–3335 (2013).10.1016/j.biomaterials.2013.01.061 ↗
26. Murakami, M. & Simons, M. Fibroblast growth factor regulation of neovascularization. Curr. Opin. Hematol. 15, 215–220 (2008).10.1097/MOH.0b013e3282f97d98 ↗
27. Cross, M. J. & Claesson-Welsh, L. FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol. Sci. 22, 201–207 (2001).10.1016/S0165-6147(00)01676-X ↗
28. Lin, S. et al. IGF-1 promotes angiogenesis in endothelial cells/adipose-derived stem cells co-culture system with activation of PI3K/Akt signal pathway. Cell Prolif. 50, e12390 (2017).10.1111/cpr.12390 ↗
29. Huang, Q., Liu, B. & Wu, W. Biomaterial-based bFGF delivery for nerve repair. Oxid. Med. Cell. Longev. 2023, 8003821 (2023).10.1155/2023/8003821 ↗
30. Rabinovsky, E. D. The multifunctional role of IGF-1 in peripheral nerve regeneration. Neurol. Res. 26, 204–210 (2004).10.1179/016164104225013851 ↗
31. Brunet, A., Goodell, M. A. & Rando, T. A. Ageing and rejuvenation of tissue stem cells and their niches. Nat. Rev. Mol. Cell Biol. 24, 45–62 (2023).10.1038/s41580-022-00510-w ↗
32. Conboy, I. M., Conboy, M. J., Smythe, G. M. & Rando, T. A. Notch-mediated restoration of regenerative potential to aged muscle. Science 302, 1575–1577 (2003).10.1126/science.1087573 ↗
33. Reed, M. J. & Edelberg, J. M. Impaired angiogenesis in the aged. Sci. Aging Knowledge Environ. 2004, pe7 (2004).10.1126/sageke.2004.7.pe7 ↗
34. Hepple, R. T. & Rice, C. L. Innervation and neuromuscular control in ageing skeletal muscle. J. Physiol. 594, 1965–1978 (2016).10.1113/JP270561 ↗
35. Verdú, E., Ceballos, D., Vilches, J. J. & Navarro, X. Influence of aging on peripheral nerve function and regeneration. J. Peripher. Nerv. Syst. 5, 191–208 (2000).10.1111/j.1529-8027.2000.00026.x ↗
36. Apel, P. J. et al. Effect of locally delivered IGF-1 on nerve regeneration during aging: an experimental study in rats. Muscle Nerve 41, 335–341 (2010).10.1002/mus.21485 ↗
37. Alcazar, C. A., Hu, C., Rando, T. A., Huang, N. F. & Nakayama, K. H. Transplantation of insulin-like growth factor-1 laden scaffolds combined with exercise promotes neuroregeneration and angiogenesis in a preclinical muscle injury model. Biomater. Sci. 8, 5376–5389 (2020).10.1039/D0BM00990C ↗
38. Hu, C. et al. Comparative effects of basic fibroblast growth factor delivery or voluntary exercise on muscle regeneration after volumetric muscle loss. Bioengineering 9, 37 (2022).10.3390/bioengineering9010037 ↗
39. Baker, H. B. et al. Cell and growth factor-loaded keratin hydrogels for treatment of volumetric muscle loss in a mouse model. Tissue Eng. Part A 23, 572–584 (2017).10.1089/ten.tea.2016.0457 ↗
40. Passipieri, J. A. et al. Keratin hydrogel enhances in vivo skeletal muscle function in a rat model of volumetric muscle loss. Tissue Eng. Part A 23, 556–571 (2017).10.1089/ten.tea.2016.0458 ↗
41. Zhang, F. & King, M. W. Biodegradable polymers as the pivotal player in the design of tissue engineering scaffolds. Adv. Healthc. Mater. 9, e1901358 (2020).10.1002/adhm.201901358 ↗
42. Okada-Ban, M., Thiery, J. P. & Jouanneau, J. Fibroblast growth factor-2. Int. J. Biochem. Cell Biol. 32, 263–267 (2000).10.1016/S1357-2725(99)00133-8 ↗
43. Ahmad, S. S., Ahmad, K., Lee, E. J., Lee, Y.-H. & Choi, I. Implications of insulin-like growth factor-1 in skeletal muscle and various diseases. Cells 9, 1773 (2020).10.3390/cells9081773 ↗
44. Konttinen, Y. T. et al. Fibroblast biology. Signals targeting the synovial fibroblast in arthritis. Arthritis Res. 2, 348–355 (2000).10.1186/ar111 ↗
45. Wabitsch, M., Hauner, H., Heinze, E. & Teller, W. M. The role of growth hormone/insulin-like growth factors in adipocyte differentiation. Metab. Clin. Exp. 44, 45–49 (1995).10.1016/0026-0495(95)90220-1 ↗
46. Zittermann, S. I. & Issekutz, A. C. Basic fibroblast growth factor (bFGF, FGF-2) potentiates leukocyte recruitment to inflammation by enhancing endothelial adhesion molecule expression. Am. J. Pathol. 168, 835–846 (2006).10.2353/ajpath.2006.050479 ↗
47. Smith, T. J. Insulin-like growth factor-I regulation of immune function: a potential therapeutic target in autoimmune diseases? Pharmacol. Rev. 62, 199–236 (2010).10.1124/pr.109.002469 ↗
48. Charville, G. W. et al. Ex vivo expansion and in vivo self-renewal of human muscle stem cells. Stem Cell Rep. 5, 621–632 (2015).10.1016/j.stemcr.2015.08.004 ↗
49. Zhao, S. et al. Induced pluripotent stem cells for tissue-engineered skeletal muscles. Int. J. Mol. Sci. 24, 11520 (2023).10.3390/ijms241411520 ↗
50. Eugenis, I. et al. Scalable macroporous hydrogels enhance stem cell treatment of volumetric muscle loss. Biomaterials 290, 121818 (2022).10.1016/j.biomaterials.2022.121818 ↗
51. Liu, L., Cheung, T. H., Charville, G. W. & Rando, T. A. Isolation of skeletal muscle stem cells by fluorescence-activated cell sorting. Nat. Protoc. 10, 1612–1624 (2015).10.1038/nprot.2015.110 ↗
52. Kang, J. et al. Depletion of SAM leading to loss of heterochromatin drives muscle stem cell ageing. Nat. Metab. 6, 153–168 (2024).10.1038/s42255-023-00955-z ↗
53. Conchinha, N. V. et al. Protocols for endothelial cell isolation from mouse tissues: brain, choroid, lung, and muscle. STAR Protoc. 2, 100508 (2021).10.1016/j.xpro.2021.100508 ↗
54. Tabula Sapiens Consortium et al. The Tabula Sapiens: a multiple-organ, single-cell transcriptomic atlas of humans. Science 376, eabl4896 (2022).10.1126/science.abl4896 ↗