Post-stroke timing of ecm hydrogel implantation affects biodegradation and tissue restoration

Corina Damian, Harmanvir Ghuman, Carrinton Mauney, Reem Azar, Janina Reinartz, Stephen F. Badylak, Michel Modo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Extracellular matrix (ECM) hydrogel promotes tissue regeneration in lesion cavities after stroke. However, a bioscaffold’s regenerative potential needs to be considered in the context of the evolving pathological environment caused by a stroke. To evaluate this key issue in rats, ECM hydrogel was delivered to the lesion core/cavity at 7-, 14-, 28-, and 90-days post-stroke. Due to a lack of tissue cavitation 7-days post-stroke, implantation of ECM hydrogel did not achieve a sufficient volume and distribution to warrant comparison with the other time points. Biodegradation of ECM hydrogel implanted 14-and 28-days post-stroke were efficiently (80%) degraded by 14-days postbioscaffold implantation, whereas implantation 90-days post-stroke revealed only a 60% decrease. Macrophage invasion was robust at 14-and 28-days post-stroke but reduced in the 90-days poststroke condition. The pro-inflammation (M1) and pro-repair (M2) phenotype ratios were equivalent at all time points, suggesting that the pathological environment determines macrophage invasion, whereas ECM hydrogel defines their polarization. Neural cells (neural progenitors, neurons, astrocytes, oligodendrocytes) were found at all time points, but a 90-days post-stroke implantation resulted in reduced densities of mature phenotypes. Brain tissue restoration is therefore dependent on an efficient delivery of a bioscaffold to a tissue cavity, with 28-days post-stroke producing the most efficient biodegradation and tissue regeneration, whereas by 90-days post-stroke, these effects are significantly reduced. Improving our understanding of how the pathological environment influences biodegradation and the tissue restoration process is hence essential to devise engineering strategies that could extend the therapeutic window for bioscaffolds to repair the damaged brain.

Original languageEnglish
Article number11372
JournalInternational Journal of Molecular Sciences
Volume22
Issue number21
DOIs
StatePublished - 1 Nov 2021
Externally publishedYes

Keywords

  • Biodegradation
  • Biomaterial
  • Cell invasion
  • Extracellular matrix
  • Hydrogel
  • Regeneration
  • Scaffold
  • Stroke
  • Therapeutic window
  • Tissue repair

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