Phase-separated chitosan-fibrin microbeads for cell delivery

Matrix-enhanced delivery of cells is a promising approach to improving current cell therapies. Our objective was to create cell-laden composite microbeads that combine the attractive features of the natural polymers chitosan and fibrin. Liquid polydimethylsiloxane was used to emulsify a chitosan-fibrinogen solution containing suspended human fibroblast cells, followed by initiation of thrombin-mediated polymerization of fibrin and thermal/pH-mediated gelation of chitosan. Chitosan/fibrin weight percent (wt%) ratios of 100/0, 75/25, 50/50 and 25/75 were investigated. Microbead diameters ranged from 275 +/- 99 mu m to 38 +/- 10 mu m using impeller speeds from 600 to 1400 rpm. Fibroblasts remained viable on day 1 post-fabrication in all matrices, but cell viability was markedly higher in high-fibrin microbeads by day 8 post-fabrication. Cell spreading and interaction with the extracellular matrix was also markedly increased in high-fibrin matrices. Such composite microbeads containing viable entrapped cells have potential for minimally invasive delivery of cells for a variety of tissue repair applications.