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Control of Pore Size and Morphology in Collagen Microspheres

Published online by Cambridge University Press:  15 February 2011

Gennaro J. Maffia
Gennaro J. Maffia*
Affiliation:
Widener University, Department of Chemical EngineeringOne University Place, Chester, PA 19013
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Abstract

Collagen microspheres are used to immobilize mammalian and hybridoma cells in commercial cell culture in a continuous fluidized bed bioreactor. One advantage of this technology is the high cell densities and the resulting high reactor volume productivity. Cell densities have exceeded 108 cells per milliliter of reactor volume in steady state culture of CHO cells. The microsphere is manufactured in a multi-stage batch process that initially involves pretreating insoluble, Type I bovine hide collagen to remove fats, triglycerides and any soluble compounds. The collagen fibers are then milled and dispersed in an acid solution. Water to collagen ratios of 500/1, mass basis, have been achieved. Stainless steel weighting material is blended in the collagen dispersion in order to control the specific gravity. The dispersion is cast into droplets which are in turn frozen, thermally soaked, lyophilized, fractionated by terminal velocity, crosslinked and finally sterilized. The morphology and pore size are created during the soaking phase, wherein the completely frozen collagen dispersion is partially melted to provide a mobile phase for the collagen fibrils to rearrange. In their dispersed form, collagen fibrils have additional uses in separation and purification due to the ability to precisely control the swelling and collapsing by pH, surface area and concentration.

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 331: Symposium T – Biomaterials for Drug and Cell Delivery , 1993 , 53
Copyright
Copyright © Materials Research Society 1994

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