In vivo evaluation of engineered self-assembling silk fibroin hydrogels after intracerebral injection in a rat stroke model

Natalia Gorenkova, Ibrahim Osama, F. Philipp Seib, Hilary Carswell

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Targeting the brain cavity formed by an ischaemic stroke is appealing for many regenerative treatment strategies, but requires a robust delivery technology. We hypothesised that self-assembling silk fibroin hydrogels could serve as a reliable support matrix for regeneration in the stroke cavity. We therefore performed in vivo evaluation studies of self-assembling silk fibroin hydrogels after intracerebral injection in a rat stroke model. Adult male Sprague Dawley rats (n=24) underwent transient middle cerebral artery occlusion (MCAo) 2 weeks before random assignment to either no stereotaxic injection or a stereotaxic injection of either self-assembling silk fibroin hydrogels (4% w/v) or PBS into the lesion cavity. The impact on morbidity and mortality, space conformity, interaction with glial scar, interference with inflammatory response and cell proliferation in the lesion cavity were examined for up to 7 weeks by a blinded investigator. Self-assembling hydrogels filled the stroke cavity with excellent space conformity and presented neither an overt microglial/macrophage response nor an adverse morbidity or mortality. The relationship between the number of proliferating cells and lesion volume was significantly changed by injection of self-assembling silk hydrogels. This in vivo stroke model confirmed that self-assembling silk fibroin hydrogels provide a favourable microenvironment as a future support matrix in the stroke cavity.
LanguageEnglish
Number of pages11
JournalACS Biomaterials Science & Engineering
Early online date27 Nov 2018
DOIs
Publication statusE-pub ahead of print - 27 Nov 2018

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Fibroins
Hydrogels
Silk
Rats
Macrophages
Cell proliferation
Brain

Keywords

  • middle cerebral artery occlusion
  • biomaterials
  • silk
  • hydrogel

Cite this

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title = "In vivo evaluation of engineered self-assembling silk fibroin hydrogels after intracerebral injection in a rat stroke model",
abstract = "Targeting the brain cavity formed by an ischaemic stroke is appealing for many regenerative treatment strategies, but requires a robust delivery technology. We hypothesised that self-assembling silk fibroin hydrogels could serve as a reliable support matrix for regeneration in the stroke cavity. We therefore performed in vivo evaluation studies of self-assembling silk fibroin hydrogels after intracerebral injection in a rat stroke model. Adult male Sprague Dawley rats (n=24) underwent transient middle cerebral artery occlusion (MCAo) 2 weeks before random assignment to either no stereotaxic injection or a stereotaxic injection of either self-assembling silk fibroin hydrogels (4{\%} w/v) or PBS into the lesion cavity. The impact on morbidity and mortality, space conformity, interaction with glial scar, interference with inflammatory response and cell proliferation in the lesion cavity were examined for up to 7 weeks by a blinded investigator. Self-assembling hydrogels filled the stroke cavity with excellent space conformity and presented neither an overt microglial/macrophage response nor an adverse morbidity or mortality. The relationship between the number of proliferating cells and lesion volume was significantly changed by injection of self-assembling silk hydrogels. This in vivo stroke model confirmed that self-assembling silk fibroin hydrogels provide a favourable microenvironment as a future support matrix in the stroke cavity.",
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author = "Natalia Gorenkova and Ibrahim Osama and Seib, {F. Philipp} and Hilary Carswell",
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AU - Osama, Ibrahim

AU - Seib, F. Philipp

AU - Carswell, Hilary

PY - 2018/11/27

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N2 - Targeting the brain cavity formed by an ischaemic stroke is appealing for many regenerative treatment strategies, but requires a robust delivery technology. We hypothesised that self-assembling silk fibroin hydrogels could serve as a reliable support matrix for regeneration in the stroke cavity. We therefore performed in vivo evaluation studies of self-assembling silk fibroin hydrogels after intracerebral injection in a rat stroke model. Adult male Sprague Dawley rats (n=24) underwent transient middle cerebral artery occlusion (MCAo) 2 weeks before random assignment to either no stereotaxic injection or a stereotaxic injection of either self-assembling silk fibroin hydrogels (4% w/v) or PBS into the lesion cavity. The impact on morbidity and mortality, space conformity, interaction with glial scar, interference with inflammatory response and cell proliferation in the lesion cavity were examined for up to 7 weeks by a blinded investigator. Self-assembling hydrogels filled the stroke cavity with excellent space conformity and presented neither an overt microglial/macrophage response nor an adverse morbidity or mortality. The relationship between the number of proliferating cells and lesion volume was significantly changed by injection of self-assembling silk hydrogels. This in vivo stroke model confirmed that self-assembling silk fibroin hydrogels provide a favourable microenvironment as a future support matrix in the stroke cavity.

AB - Targeting the brain cavity formed by an ischaemic stroke is appealing for many regenerative treatment strategies, but requires a robust delivery technology. We hypothesised that self-assembling silk fibroin hydrogels could serve as a reliable support matrix for regeneration in the stroke cavity. We therefore performed in vivo evaluation studies of self-assembling silk fibroin hydrogels after intracerebral injection in a rat stroke model. Adult male Sprague Dawley rats (n=24) underwent transient middle cerebral artery occlusion (MCAo) 2 weeks before random assignment to either no stereotaxic injection or a stereotaxic injection of either self-assembling silk fibroin hydrogels (4% w/v) or PBS into the lesion cavity. The impact on morbidity and mortality, space conformity, interaction with glial scar, interference with inflammatory response and cell proliferation in the lesion cavity were examined for up to 7 weeks by a blinded investigator. Self-assembling hydrogels filled the stroke cavity with excellent space conformity and presented neither an overt microglial/macrophage response nor an adverse morbidity or mortality. The relationship between the number of proliferating cells and lesion volume was significantly changed by injection of self-assembling silk hydrogels. This in vivo stroke model confirmed that self-assembling silk fibroin hydrogels provide a favourable microenvironment as a future support matrix in the stroke cavity.

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