In vitro effects of transcatheter injection on structure, cell viability, and cell metabolism in fibroblast-impregnated alginate microspheres

PURPOSE: To determine if microsphere-encapsulated cell preparations can be delivered through a microcatheter without compromising microsphere structur e, cell viability, or metabolism. MATERIALS AND METHODS: Fibroblast-impregnated microspheres were fabricated by using 1.0% alginate and rabbit synovial fibroblasts. Fibroblast-impregna ted alginate microspheres injected through microcatheters were analyzed in parallel with identical noninjected microspheres. The effects of transcathe ter injection on structure and cell viability (percentage of viable cells p er microsphere) were correlated with microsphere size. Structural effects w ere analyzed by using light microscopy, and 7-day percentage (ratio of live cells to dead cells) cell viability was assessed with confocal microscopy and fluorescent staining. In a second series of experiments, the metabolism of small microspheres was studied during a course of 7 days by using a spe ctrophotometric bioanalyzer. RESULTS: Transcatheter injection caused fracturing and/or fragmentation of large (800-1,000 mum) and medium (500-750 mum) microspheres, while small (2 50-400 mum) microspheres were structurally unaffected by transcatheter inje ction. Fracturing and fragmentation were associated with cell release from the alginate matrix. Although transcatheter injection reduced cell viabilit y by 17%-23% in all size categories, it did not cause a detectable alterati on in the rate of glucose metabolism. CONCLUSION: Transcatheter injection was physiologically well tolerated by f ibroblasts encapsulated in alginate microspheres; however, when microsphere diameter exceeded the catheter diameter, fracturing and fragmentation of m icrospheres compromised the sequestration function of the microsphere vecto r.