Table 3 Selection of investigations carried out into potential protective mechanisms for cell cargos

From: Translational considerations in injectable cell-based therapeutics for neurological applications: concepts, progress and challenges

Aim of study

Cell type

Needle size

Flow rate

Brief description of results

Refs.

Use of hydrogels

Improving viability during injection by alginate hydrogels

Human umbilical vein endothelial cells and adipose stem cells, rat MSCs, and mouse neural progenitor cells

28 G needle on 1 mL syringes

1000 µL/min

Crosslinked alginate hydrogel produced highest viability. Increasing or decreasing G′ reduced protective effect. Cells in non-crosslinked alginate exhibited lower viabilities than media. Data suggested extensional flow at needle entrance was chief cause of cell death

52

β-hairpin peptide hydrogel as carrier during syringe flow

MG63

26 G needle on 1 mL syringe

4, 6 and 8 mL/h

Only gel at the capillary wall experienced a velocity gradient, whereas the rest was subject to minimal shear rate. Hydrogels had no apparent effect on viability of encapsulated cells

114

Injectable fibrin matrix to enhance vascularisation

Bone marrow mononuclear cells (BMMNCs)

100 µL injection—Needle size not mentioned

Not mentioned

Device was constructed for simultaneous injection of fibrinogen and thrombin solutions. Implantation of BMMNCs in fibrin resulted in better tissue regeneration and neovascularisation

123

Growth factor supplemented matrigel for cell delivery

C2C12 myoblasts

Not mentioned

Slow-exact rate not mentioned

Results showed that the combination of matrigel as a cell carrier for myoblasts with growth factors is recommended for the generation of muscle in vivo

124

Use of microparticles

PLGA particles for intracerebral delivery

Neural stem cells

22 G needle on a 50 µL gastight Luer-tip syringe

2 μL/min

Plasma polymerised allylamine-treated MPs were used. Cell attachment was influenced by curvature, material, electrostatic charge and surface motif of particles, and the number of cells in the culture

125, 126

Nerve growth factor (NGF)-releasing PLGA microparticles

Foetal rat (E16-E17) brain cells

22s-G needle on a 10 µL syringe

<1 µL/min

Dose of NGF delivered can be modified by changing quantity of microparticles or NGF release rate. Activity of neo-tissues with NGF-enriched microenvironments increased in in vivo and in vitro

127

Automated vs. manual systems

Compare manual and automated injection

Neural progenitor cells and bone marrow stromal cells

Automated device for μL syringes (MEDRAD Inc.)

—

Automated delivery resulted in less variability in amount delivered. No significant difference in viability attributable to method of injection

49

  1. G′ hydrogel storage modulus.