Hydrogel-Based Therapy for Brain Repair After Intracerebral Hemorrhage

Teck Chuan Lim; Emiri Mandeville; Ding Weng; Li-Shan Wang; Motoichi Kurisawa; Kimberly Leite-Morris; Magdy H Selim; Eng H Lo; Myron Spector

doi:10.1007/s12975-019-00721-y

Hydrogel-Based Therapy for Brain Repair After Intracerebral Hemorrhage

Transl Stroke Res. 2020 Jun;11(3):412-417. doi: 10.1007/s12975-019-00721-y. Epub 2019 Aug 20.

Authors

Teck Chuan Lim^{1

2}, Emiri Mandeville³, Ding Weng⁴, Li-Shan Wang⁵, Motoichi Kurisawa⁵, Kimberly Leite-Morris^{6

7}, Magdy H Selim⁸, Eng H Lo⁹, Myron Spector^{10

11}

Affiliations

¹ Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA. tclim@alum.mit.edu.
² Tissue Engineering Laboratories, Veterans Affairs Boston Healthcare System, Mail Stop 151, 150 S. Huntington Avenue, Boston, MA, 02130, USA. tclim@alum.mit.edu.
³ Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital-East and Harvard Medical School, Room 2401, 149 13th Street, Charlestown, MA, 02129, USA.
⁴ Tissue Engineering Laboratories, Veterans Affairs Boston Healthcare System, Mail Stop 151, 150 S. Huntington Avenue, Boston, MA, 02130, USA.
⁵ Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, #07-01, Singapore, 138669, Singapore.
⁶ Neurochemistry and Behavioral Neuroscience Laboratory, Veterans Affairs Boston Healthcare System, Boston, MA, USA.
⁷ Division of Psychiatry and Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.
⁸ Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
⁹ Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital-East and Harvard Medical School, Room 2401, 149 13th Street, Charlestown, MA, 02129, USA. lo@helix.mgh.harvard.edu.
¹⁰ Tissue Engineering Laboratories, Veterans Affairs Boston Healthcare System, Mail Stop 151, 150 S. Huntington Avenue, Boston, MA, 02130, USA. mspector@bwh.harvard.edu.
¹¹ Department of Orthopedic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. mspector@bwh.harvard.edu.

PMID: 31432328
DOI: 10.1007/s12975-019-00721-y

Abstract

We assessed an injectable gelatin hydrogel containing epidermal growth factor (Gtn-EGF) as a therapy for intracerebral hemorrhage (ICH). ICH was induced in rats via collagenase injection into the striatum. Two weeks later, Gtn-EGF was injected into the cavitary lesion. The hydrogel filled ICH cavities without deforming brain tissue. Immunostaining demonstrated that neural precursor cells could migrate into the matrix, and some of these differentiated into neurons along with the appearance of astrocytes, oligodendrocytes, and endothelial cells. Sensorimotor tests suggested that Gtn-EGF improved neurological recovery. This study provides proof-of-principle that injectable biomaterials may be a translationally relevant approach for treating ICH.

Keywords: Injectable hydrogel; Neural precursors; Stroke cavity.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Brain / drug effects*
Brain / pathology*
Cerebral Hemorrhage / drug therapy*
Cerebral Hemorrhage / pathology*
Disease Models, Animal
Drug Delivery Systems / instrumentation*
Drug Delivery Systems / methods*
Epidermal Growth Factor / administration & dosage*
Gelatin / administration & dosage
Hydrogels / administration & dosage
Male
Neuroprotective Agents / administration & dosage*
Rats, Sprague-Dawley

Substances

Hydrogels
Neuroprotective Agents
Epidermal Growth Factor
Gelatin