Dual-function injectable angiogenic biomaterial for the repair of brain tissue following stroke

Abstract

Stroke is the primary cause of disability due to the brain's limited ability to regenerate damaged tissue. After stroke, an increased inflammatory and immune response coupled with severely limited angiogenesis and neuronal growth results in a stroke cavity devoid of normal brain tissue. In the adult, therapeutic angiogenic materials have been used to repair ischaemic tissues through the formation of vascular networks. However, whether a therapeutic angiogenic material can regenerate brain tissue and promote neural repair is poorly understood. Here we show that the delivery of an engineered immune-modulating angiogenic biomaterial directly to the stroke cavity promotes tissue formation de novo, and results in axonal networks along thee generated blood vessels. This regenerated tissue produces functional recovery through the established axonal networks. Thus, this biomaterials approach generates a vascularized network of regenerated functional neuronal connections within previously dead tissue and lays the groundwork for the use of angiogenic materials to repair other neurologically diseased tissues.

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Fig. 1: Post-stroke angiogenic response and vascular remodelling.
Fig. 2: Long-term post-stroke vascular growth.
Fig. 3: Post-stroke neurogenesis and axonal sprouting.
Fig. 4: Association between the vascular and axonal networks in the lesion site.
Fig. 5: Poststroke neurological recovery.
Fig. 6: Role of naked heparin particles in the hcV treatment at 2 weeks poststroke.

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Acknowledgements

This work was supported through the US National Institutes of Health NIH RO1NS079691. The Bioplex experiment was done at the UCLA IMT core, Center for Systems Biomedicine, which is supported by CURE/P30 DK041301.

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L.R.N. was responsible for the conceptual design of the in vivo study, troubleshooting, experimental execution, interpretation of in vivo data, manuscript writing and figure creation. S.G. performed in vitro studies and interpretation, sample preparation and characterization. T.S. and S.T.C. contributed equally to overseeing experimental design and interpretation.

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Correspondence to S. Thomas Carmichael or Tatiana Segura.

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Nih, L.R., Gojgini, S., Carmichael, S.T. et al. Dual-function injectable angiogenic biomaterial for the repair of brain tissue following stroke. Nature Mater 17, 642–651 (2018). https://doi.org/10.1038/s41563-018-0083-8

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