Date of Award

1-1-2011

Document Type

Campus Access Dissertation

Department

Biomedical Engineering

First Advisor

Xiaoming He

Abstract

Micro/nano scale materials have shown great potential for a variety of applications. However, the widespread use of many of these materials for biomedical application has been restricted by their poor biocompatibility and physiological/anatomical limitations. In this study, both novel micro and nano scale biomaterials with great biocompatibility and potential for cell-based medicine and cancer treatment were developed and characterized.

Encapsulation of living cells in small microcapsules for transplantation to avoid immunorejection is critical to the success of cell-based medicine. However, existing studies on cell microencapsulation, usually using microcapsules greater than 250 µm, have been shown to be suboptimal as cells in the central region become damaged due to hypoxia and deprivation of nutrients. Therefore, small (~ 100 µm) alginate-based microcapsules were first developed using the electrostatic spray method and characterized for encapsulation of mesenchymal stem cells. Alginate was used because it is a natural polysaccharide (abundant in seaweeds) with great biocompatibility. Interestingly, encapsulation of living cells in the small alginate microcapsules significantly augments cell survival post ice-free cryopreservation (vitrification). As a result, the concentration of cryoprotectant(s) required to achieve vitrification is reduced from 4-7 M (toxic) to about 1.5 M (nontoxic). However, plain alginate microcapsules are incapable of achieving immunoisolation. To overcome this problem, the small alginate microcapsules were further coated with chitosan, a natural polysaccharide (abundant in sea food) with good biocompatibility, to obtain cell-loaded alginate-chitosan-alginate (ACA) microcapsules with high cell viability (~ 97%). The membrane of the ACA microcapsules was found to be capable of blocking immune cells/proteins to protect the encapsulated cells while allowing free diffusion of nutrients, metabolic wastes, and therapeutic agents. As a result, the encapsulated cells can survive well at least during a 1-month observation period. Taken together, the small ACA microcapsule is a promising system to encapsulate both autologous and non-autologous cells for cell-based medicine.

At the nano scale, thermally responsive Pluronic F127 based nanocapsules using chitosan as the crosslinker were synthesized. The Pluronic F127-chitosan nanocapsules were found to have excellent biocompatibility, presumably due to the biocompatible nature of the two constituent polymers. In particular, Pluronic F127 has been approved by the Food and Drug Administration (FDA) for use as food additives and pharmaceutical ingredients. Moreover, the nanocapsules were found to be capable of not only encapsulating small hydrophilic molecules for intracellular delivery but achieving temperature controlled release of the small molecules. By breaking up the endosomal membrane through temperature-dependent volume change of the nanocapsule, this novel nanomaterial may be used to achieve cytosol-specific delivery of small anticancer drugs and therapeutic agents for improved cancer treatment.

Rights

© 2011, Wujie Zhang

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