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

Gorenkova, Natalia and Osama, Ibrahim and Seib, F. Philipp and Carswell, Hilary (2018) In vivo evaluation of engineered self-assembling silk fibroin hydrogels after intracerebral injection in a rat stroke model. ACS Biomaterials Science & Engineering. ISSN 2373-9878

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    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.