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Hydrogel Scaffolds: Towards Restitution of Ischemic Stroke-Injured Brain

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Abstract

Chronic brain injury following cerebral ischemia is a severe debilitating neurological condition, where clinical intervention is well known to decrease morbidity and mortality. Despite the development of several therapeutic strategies, clinical outcome in the majority of patients could be better improved, since many still face life-long neurological deficits. Among the several strategic options that are currently being pursued, tissue engineering provides much promise for neural tissue salvage and regeneration in brain ischemia. Specifically, hydrogel biomaterials have been utilized to docket biomolecules, adhesion motifs, growth factors, and other proneural cues for stable stem cell encapsulation. Here, we provide an overview of therapeutic applications of hydrogels in stroke treatment. Special focus is given to design considerations for generation of efficient hydrogel systems for neurological applications. Therapeutic applications of hydrogels in stroke as conducive microenvironments for stem cell transplantation and drug delivery have been discussed. Finally, we present our perspectives on clinical translation of hydrogels for neural tissue regeneration.

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Abbreviations

BBB :

Blood blood-brain barrier

3D :

Three-dimensional

CNS :

Central nervous system

ECM :

Extracellular matrix

HA :

Hyaluronic acid

GAG :

Glycoseaminoglycans

ECF :

Extracellular fluid

PEG :

poly(ethylene glycol)

N-CAM :

Neural cell adhesion molecule

hNPCs :

Human neural progenitor cells

MMP :

Matrix metalloproteinase

BMP-4 :

Bone morphogenic protein-4

BDNF :

Brain-derived neurotrophic factor

iPSCs :

Induced pluripotent stem cells

iPSC-NPCs :

iPSC-derived NPCs

RGD :

Arginine-glycine-aspartic acid

ELPs :

Elastin-like peptides

NSC :

Neural stem cell

hPSC :

Human pluripotent stem cell

hUVECs :

Human umbilical vein endothelial cells

CAM :

Chorioallantoic membrane

E :

Elastic modulus

NSPCs :

Neural stem and progenitor cells

MAC :

Methacrylamide chitosan

UBM :

Urinary bladder matrix

EGF :

Epidermal growth factor

PPy :

polypyrrole

VEGF :

Vascular endothelial growth factor

HepMA :

Heparin methacrylate

PVA :

poly(vinyl alcohol)

PEDOT :

poly(3,4-ethylenedioxythiophene)

pTS :

paratoluenesulfonate

PANI :

polyaniline

p(GMA) :

poly(glyceryl methacrylate)

PHPMA :

poly(N-2-hydroxypropyl methacrylamide)

PEGDA :

poly(ethyleneglycol diacrylate)

LCST :

Lower critical solution temperature

UCST :

Upper critical solution temperature

pNIPAAm :

poly(N-isopropylacrylamide)

PLLA :

poly-l-(lactic acid)

PEO-PPO-PEO :

poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide)

pNIPAAm-PEG :

pNIPAAm grafted PEG

PUASM :

poly(urethane amino sulfamethazine)

S-NBC :

S-(2-nitrobenzyl)cysteine)

GRGDS :

Gly-Arg-Gly-Asp-Ser

EPO :

Erythropoietin

G-CSF :

Granulocyte colony-stimulating factor

HAMC :

Hyaluronan/methyl cellulose

PLGA :

poly(lactic-co-glycolic acid)

PDMS-TEOS :

polydimethysiloxane-tetraethoxysilane

Ang-1 :

Angiopoietin-1

ESC :

Embryonic stem cell

PCL :

polycaprolactone

GSH :

Genipin cross-linked sericin hydrogel

hEnSCs :

Human endometrial stem cells

SCs :

Schwann cells

PFTBA :

perfluorotributylamine

MRI :

Magnetic resonance imaging

PET :

Positron emission tomography

BLI :

Bioluminescence imaging

CEST:

Chemical exchange saturation transfer

GLP-1 :

Glucagon-like peptide-1

STEP :

Striatal enriched tyrosine phosphatase

TBI :

Traumatic brain injury

hUC-MSCs :

Human umbilical cord mesenchymal stem cells

SDF-1α :

Stromal cell-derived factor 1α

CS-GAG :

Chondroitin sulfate glycosaminoglycan

SCI :

Spinal cord injury

NGF :

Nerve growth factor

hUTCs :

Human umbilical tissue-derived cells

VM :

Ventral midbrain

DA :

Dopamine

BDNF-His :

Hexahistidine peptide-linked recombinant BDNF

PD :

Parkinson’s disease

PAA :

poly(amidoamine)

TH :

Tyrosine hydroxylase

GBM :

Glioblastoma

GemC12 :

Gemcitabine

ICG :

Indocyanine green

PEG-DMA :

polyethylene glycol dimethacrylate

TMZ :

Temozolomide

PC gel :

poly(ethylene glycol)-g-chitosan hydrogel

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  1. School of Biotechnology, National Institute of Technology Calicut, Calicut, 673601, India

    Aswathi Gopalakrishnan & G. K. Rajanikant

  2. Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham, Kochi, 682041, India

    Sahadev A. Shankarappa

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Gopalakrishnan, A., Shankarappa, S.A. & Rajanikant, G.K. Hydrogel Scaffolds: Towards Restitution of Ischemic Stroke-Injured Brain. Transl. Stroke Res. 10, 1–18 (2019). https://doi.org/10.1007/s12975-018-0655-6

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