Background: Silk has been used in humans for centuries and is a FDA approved biomaterial for load bearing applications. Silk has a strong clinical track record and is widely regarded as biocompatible and biodegradable; reverse engineered silk can be processed into many material formats, including self-assembling silk hydrogels. These silk hydrogels are emerging as a promising delivery platform for both drugs and cells, but have never been tested in the brain. Aim: To investigate in vivo distribution, biocompatibility and biodegradation of the self-assembling silk hydrogel in the brain after experimental stroke. Methods: 22 male adult Sprague Dawley rats underwent transient middle cerebral artery occlusion and randomly selected to receive no treatment, vehicle or silk hydrogel (4 % w/v) implant 2 weeks later. Animals were randomly selected for termination at 1 week (subacute) or 7 weeks (chronic) time point. Tissue loss and silk graft were detected using haematoxylin and eosin (H&E) staining and quantified by image analysis. Glial scar formation and graft distribution were measured using GFAP and DAPI nuclear staining. Results: Self-assembling silk hydrogels were able to fill the stroke cavity, were present at the site of application 7 weeks post application and were well integrated into the host tissues. GFAP and H&E detected no inflammation in the brain in response to the silk hydrogel (1 or 7 weeks postgrafting). There was partial host cell infiltration into the silk hydrogel as revealed by nuclei staining. Conclusions: Silk hydrogels are emerging as a biocompatible biomaterials in the stroke setting. Furthermore, silk hydrogels showed excellent space conformity; all necessary requirements to successfully deliver a therapeutic playload. Further studies are ongoing to establish if host cell infiltration is due to neurogenesis or inflammatory cells. Post?graft survival within the cavity at 7 weeks indicates the potential of silk hydrogels to promote new neurovascular niche formation.
|Number of pages||1|
|Journal||Journal of Cerebral Blood Flow and Metabolism|
|Publication status||Published - 1 Apr 2017|
|Event||28th International Symposium on cerebral blood flow, metabolism and function/13th international conference on quantification of brain function with PET - Berlin, Berlin, Germany|
Duration: 1 Apr 2017 → 4 Apr 2017
- silk hydrogels