Evaluating the Feasibility of Hydrogel-Based Neural Cell Sprays

Abstract

Neurological injuries have poor prognoses with serious clinical sequelae. Stem cell transplantation enhances neural repair but is hampered by low graft survival (<ca. 5%), necessitating the development of approaches to enhance post-transplant cell viability. Intracerebral injection exerts high mechanical forces on transplant cells with risks of haemorrhage/infection. Transplant cell sprays can offer a non-invasive alternative. This study has assessed if the addition of protective, encapsulating polymer hydrogels to a cell spray format is feasible. Hydrogels (0.1% (1 mg/mL), 0.3% and 0.6% type I rat tail collagen) were trialled for spray deliverability. Cell-enriched hydrogels (containing mouse cortical astrocytes) were sprayed onto culture substrates. Astrocyte viability, cell-specific marker expression, morphology and proliferation were assessed at 24 h and 72 h post spraying. Intra-gel astrocytes and hydrogels could be co-stained using a double immunocytological technique (picrosirius red (PR)/DAB-peroxidase co-labelling). Astrocyte viability remained high post spraying with hydrogel encapsulation (>ca. 80%) and marker expression/proliferative potential of hydrogel-sprayed astrocytes was retained. Combining a cell spray format with polymer encapsulation technologies could form the basis of a non-invasive graft delivery method, offering potential advantages over current cell delivery approaches.