Collagen hydrogels loaded with fibroblast growth factor-2 as a bridge to repair brain vessels in organotypic brain slice
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RESEARCH ARTICLE
Collagen hydrogels loaded with fibroblast growth factor‑2 as a bridge to repair brain vessels in organotypic brain slices Buket Ucar1 · Sedef Yusufogullari1,2 · Christian Humpel1 Received: 10 April 2020 / Accepted: 14 August 2020 © The Author(s) 2020
Abstract Vessel damage is a general pathological process in many neurodegenerative disorders, as well as spinal cord injury, stroke, or trauma. Biomaterials can present novel tools to repair and regenerate damaged vessels. The aim of the present study is to test collagen hydrogels loaded with different angiogenic factors to study vessel repair in organotypic brain slice cultures. In the experimental set up I, we made a cut on the organotypic brain slice and tested re-growth of laminin + vessels. In the experimental set up II, we cultured two half brain slices with a gap with a collagen hydrogel placed in between to study endothelial cell migration. In the experimental set up I, we showed that the number of vessels crossing the cut was tendencially increased with the addition of fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor, or platelet-derived growth factor-BB compared to the control group. In the experimental set up II, we demonstrated that a collagen hydrogel loaded with FGF-2 resulted in a significantly increased number of migrated laminin + cells in the gap between the slices compared to the control hydrogel. Co-administration of several growth factors did not further potentiate the effects. Taken together, we show that organotypic brain slices are good models to study brain vessels and FGF-2 is a potent angiogenic factor for endothelial cell proliferation and migration. Our results provide evidence that the collagen hydrogels can be used as an extracellular matrix for the vascular endothelial cells. Keywords Brain vessel · Repair · Collagen hydrogel · Organotypic brain slices · Fibroblast growth factor-2
Introduction The human brain contains approximately 650 km-long capillaries, so much that it is estimated that each neuron is perfused by its own capillary (Zlokovic 2005; Cipolla 2009). The brain capillary network includes primarily endothelial cells and pericytes, which are surrounded by astrocytic endfeet, forming a neurovascular unit (Cipolla 2009). Endothelial cells line all the vessels from big arteries and veins to the smallest capillaries in the whole body, regulating the Communicated by Thomas Deller. * Christian Humpel christian.humpel@i‑med.ac.at 1
Laboratory of Psychiatry and Experimental Alzheimer’s Research, Department of Psychiatry and Psychotherapy, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
Biomedical Institute, Gebze Technical University, Istanbul, Turkey
2
diffusion of molecules in circulation. Brain endothelial cells form the blood–brain barrier (BBB) and tightly regulate the transport between the brain and the periphery. Proper functioning of neurons depends on this tight regulation of the extracellular environment and impairments of BBB disrupts central ner
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