Improving Treatment of Stroke through Nanotechnology

Nicholls, Francesca J.; Gorenkova, Natalia; Bible, Ellen; Franco, Christy L.; Chau, David; Tolias, Christos M.; Shakesheff, Kevin M.; West, Jennifer; Modo, Mike

doi:10.1201/b15274-22

Cited by 2 publications

(3 citation statements)

References 109 publications

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“…Given the adverse effects associated with some biomaterials in vivo, ,, we first tested for any potential overt behavioral effects following implantation of 4% w/v silk fibroin hydrogels into the stroke cavity; this selected silk fibroin concentration results in hydrogels with similar mechanical properties of healthy brain tissue (Figure S3). At 2 weeks post-MCAo, the silk fibroin hydrogel graft had no significant effect on body weight or neurological score when compared to the no graft control or PBS, implying no overt adverse effects of intracranial silk fibroin hydrogels.…”

Section: Discussionmentioning

confidence: 99%

“…Biomaterials are ideally placed to serve this function. , For example, biomaterials can replace the lost 3D microenvironment by physically filling the lesion cavity, mimicking brain ECM and supporting endogenous repair mechanisms. , They can also serve as a potential delivery matrix for therapeutics payloads . To date, several studies have shown encouraging results following the use of synthetic biomaterials in preclinical models of stroke .…”

Section: Introductionmentioning

confidence: 99%

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In Vivo Evaluation of Engineered Self-Assembling Silk Fibroin Hydrogels after Intracerebral Injection in a Rat Stroke Model

Gorenkova

Osama

Seib

et al. 2018

ACS Biomater. Sci. Eng.

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Targeting the brain cavity formed by an ischemic stroke is appealing for many regenerative treatment strategies but requires a robust delivery technology. We hypothesized 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 favorable microenvironment as a future support matrix in the stroke cavity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In Vivo Evaluation of Engineered Self-Assembling Silk Fibroin Hydrogels after Intracerebral Injection in a Rat Stroke Model

Gorenkova

Osama

Seib

et al. 2018

ACS Biomater. Sci. Eng.

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“…However, it is unclear if this is indeed due to a repair of the lesion cavity or by promoting changes in the host parenchyma. Nevertheless, implantation of biomaterials into the stroke cavity offers the opportunity to deliver large quantities of neuroprotective factors locally in the area of damage, potentially avoiding side effects if these factors were delivered systemically [49]. The combination of functionalized biomaterials and transplanted cells introduces novel opportunities to potentially repair stroke-induced tissue damage.…”

Section: Discussionmentioning

confidence: 99%

Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by 19F- and diffusion-MRI

et al. 2012

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Transplantation of human neural stem cells (hNSCs) is emerging as a viable treatment for stroke related brain injury. However, intraparenchymal grafts do not regenerate lost tissue, but rather integrate into the host parenchyma without significantly affecting the lesion cavity. Providing a structural support for the delivered cells appears important for cell based therapeutic approaches. The non-invasive monitoring of therapeutic methods would provide valuable information regarding therapeutic strategies but remains a challenge. Labeling transplanted cells with metal-based 1H-magnetic resonance imaging (MRI) contrast agents affects the visualization of the lesion cavity. Herein, we demonstrate that a 19F-MRI contrast agent can adequately monitor the distribution of transplanted cells, whilst allowing an evaluation of the lesion cavity and the formation of new tissue on 1H-MRI scans. Twenty percent of cells labeled with the 19F-agent were of host origin, potentially reflecting the re-uptake of label from dead transplanted cells. Both T2- and diffusion-weighted MRI scans indicated that transplantation of hNSCs suspended in a gel form of a xenogeneic extracellular matrix (ECM) bioscaffold resulted in uniformly distributed cells throughout the lesion cavity. However, diffusion MRI indicated that the injected materials did not yet establish diffusion barriers (i.e. cellular network, fiber tracts) normally found within striatal tissue. The ECM bioscaffold therefore provides an important support to hNSCs for the creation of de novo tissue and multi-nuclei MRI represents an adept method for the visualization of some aspects of this process. However, significant developments of both the transplantation paradigm, as well as regenerative imaging, are required to successfully create new tissue in the lesion cavity and to monitor this process non-invasively.

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Improving Treatment of Stroke through Nanotechnology

Cited by 2 publications

References 109 publications

In Vivo Evaluation of Engineered Self-Assembling Silk Fibroin Hydrogels after Intracerebral Injection in a Rat Stroke Model

In Vivo Evaluation of Engineered Self-Assembling Silk Fibroin Hydrogels after Intracerebral Injection in a Rat Stroke Model

Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by 19F- and diffusion-MRI

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