Controlling Diffusion of Solutes Through Ionically Crosslinked Alginate Hydrogels Designed for Tissue Engineering
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Controlling Diffusion of Solutes through Ionically Crosslinked Alginate Hydrogels Designed for Tissue Engineering Catherine K. Kuo1,2 and Peter X. Ma1,2,3 1 Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109-1078, USA; 2 Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI; 3 Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI
ABSTRACT Tissue engineering aims at creating new tissues as alternatives to organ transplants. Our approach is to incorporate cells into biodegradable polymer scaffolds designed to temporarily support new tissue formation. An important requirement of scaffolds is homogeneity. Homogeneity ensures structural integrity, uniform distribution of cells, and uniform porosity throughout the scaffold. Controlling pore sizes is necessary to regulate exchange of nutrients and waste products for cells. Pores too large can provide entryway to immune cells that can harm allogenic cells and developing tissue. We have fabricated three-dimensionally defined, homogeneous, ionically crosslinked alginate gels with a controlled slow-gelation system involving CaCO3 and D-glucono-δ-lactone. We varied the structural parameters and alginate types of these gels to control the diffusion of glucose, vitamin B12 and FITC-dextran (molecular weights of 180, 1355 and 9500, respectively) through the gels. Experiments were performed with gel discs placed between side-by-side donor and receptor chambers in a humidified incubator at 37°C. Samples were taken periodically and measured on a UV-Vis spectrophotometer. Generally, diffusion coefficient (D) increased with decreasing solute size. Varying structural parameters of the gels did not have a significant effect on diffusivity of vitamin B12. In contrast, for gels made with a Ca2+ to carboxyl molar ratio of 0.36, D of FITCdextran increased from (2.88 ± 0.52)×10-7 to (4.66 ± 0.48)×10-7 cm2/sec as alginate concentration decreased from 3.2% to 1.5%, respectively. D of FITC-dextran also increased from (3.17 ± 0.30)×10-7 to (4.66 ± 0.48)×10-7 cm2/sec as crosslinking density decreased for 1.5% alginate gels from a Ca2+ to carboxyl molar ratio of 0.72 to 0.36, respectively. D was highest for alginate gels with the highest guluronic acid content. Controlling diffusivity allows alginate gels with specific properties to be fabricated for tissue engineering scaffolding and other biomedical applications.
INTRODUCTION Various synthetic and natural materials have been used to create synthetic extracellular matrices for tissue replacement [1-4]. The scaffolds act as skeletal structures for cell attachment and growth to facilitate tissue regeneration. A well-designed tissue engineering scaffold will optimize cell survival and tissue formation conditions with proper assimilation of the matrix and the developing new tissue. Homogeneity of the scaffold ensures structural integrity, uniform porosity throughout the scaffold and also uniform distribution of the cells. Control over porosity and pore size
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