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In Vitro Effects of Transcatheter Injection on Structure, Cell Viability, and Cell Metabolism in Fibroblast-impregnated Alginate Microspheres¹

¹ From the Section of Interventional Neuroradiology (T.A., H.J.C., G.G.S., J.E.D.) and Division of Radiological Sciences (S.M.W., I.C.), Department of Radiology, Emory University School of Medicine, 1364 Clifton Rd NE, Atlanta, GA 30302; School of Chemical Engineering and P. H. Parker Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta (A.S.); and Division of Interventional Neuroradiology, Department of Radiology, University of Virginia Health Sciences Center, Charlottesville (D.F.K.). Received August 3, 2000; revision requested September 19; revision received December 19; accepted January 26, 2001. Supported by a grant from the Emory University/Georgia Institute of Technology Biomedical Research Center. H.J.C. supported in part the RSNA Research and Education Foundation as a 1999 Sterling Diagnostic/RSNA Scholar. Address correspondence to T.A. (e-mail: tabruzz@emory.edu).

PURPOSE: To determine if microsphere-encapsulated cell preparations can be delivered through a microcatheter without compromising microsphere structure, cell viability, or metabolism.

MATERIALS AND METHODS: Fibroblast-impregnated microspheres were fabricated by using 1.0% alginate and rabbit synovial fibroblasts. Fibroblast-impregnated alginate microspheres injected through microcatheters were analyzed in parallel with identical noninjected microspheres. The effects of transcatheter injection on structure and cell viability (percentage of viable cells per microsphere) were correlated with microsphere size. Structural effects were 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 spectrophotometric bioanalyzer.

RESULTS: Transcatheter injection caused fracturing and/or fragmentation of large (800–1,000 µm) and medium (500–750 µm) microspheres, while small (250–400 µm) microspheres were structurally unaffected by transcatheter injection. Fracturing and fragmentation were associated with cell release from the alginate matrix. Although transcatheter injection reduced cell viability by 17%–23% in all size categories, it did not cause a detectable alteration in the rate of glucose metabolism.

CONCLUSION: Transcatheter injection was physiologically well tolerated by fibroblasts encapsulated in alginate microspheres; however, when microsphere diameter exceeded the catheter diameter, fracturing and fragmentation of microspheres compromised the sequestration function of the microsphere vector.

Index terms: Microspheres • Experimental study

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