Identifier

etd-11102011-181211

Degree

Doctor of Philosophy (PhD)

Department

Engineering Science (Interdepartmental Program)

Document Type

Dissertation

Abstract

The development of porous materials useful as scaffolds for the sustained three-dimensional (3D) growth of human adipose-derived stem cells (hASC) is of particular interest to facilitate healing after musculoskeletal injuries. In this study, a composite porous material obtained by blending akermanite with poly-e-caprolactone (PCL) is proposed as novel alternative to bone tissue regeneration. The objectives of this study are (1) to characterize the akermanite:PCL scaffold properties; (2) to investigate the in vitro osteogenic potential of hASC loaded to optimal akermanite:PCL scaffolds; (3) to assess the metabolic activity and osteogenesis of hASC loaded to optimal akermanite:PCL scaffolds post-thawing using optimal cryopreservation protocol; and (4) to evaluate the behavior of optimal akermanite:PCL scaffolds in vivo using an immunodeficient murine model for ectopic bone formation. We hypothesized that (1) optimal akermanite:PCL blend has mechanical properties and biocompatibility suitable for tissue engineering applications; (2) hASC loaded to optimal akermanite:PCL scaffolds has higher expression of mature osteogenic marker in scaffolds cultured in osteogenic medium for 21 days; (3) PVP-serum free medium can be used to cryopreserve hASC loaded to optimal akermanite:PCL scaffolds; and (4) hASC preloaded to optimal akermanite:PCL scaffolds would produce meaningful bone-like tissue 8 weeks post-implantation. According to the results, 75:25 akermanite:PCL composite scaffolds displayed increased mechanical (1), biological and osteogenic properties (1-3). Moreover, hASC loaded to 75:25 akermanite:PCL scaffolds and frozen at 40ᵒC/min displayed metabolic activity and osteogenesis comparable to fresh control scaffolds (3). However, in vivo implantation of akermanite-base scaffolds (akermanite and akermanite:PCL) in nude mice, sudden death within the first 48 hours of this study (4). The acute toxicity observed in all animals assigned to the akermanite scaffolds was associated to a disturbance of the phosphorus homeostasis in vivo. Specifically, akermanite and akermanite:PCL scaffolds harvested 48 hours post-implantation had comparable levels of phosphorous in the composition, indicating acute phosphorous depletion from the serum. Accumulative evidences have suggested that akermanite is biocompatible and can enhance adhesion, proliferation and osteogenic phenotype maintenance of adult/osteoprogenitor stem cells both in vitro and in vivo. As a conclusion, further studies are needed to address the akermanite dose-dependent toxicity in murine models for akermanite-assisted bone regeneration.

Date

2011

Document Availability at the Time of Submission

Secure the entire work for patent and/or proprietary purposes for a period of one year. Student has submitted appropriate documentation which states: During this period the copyright owner also agrees not to exercise her/his ownership rights, including public use in works, without prior authorization from LSU. At the end of the one year period, either we or LSU may request an automatic extension for one additional year. At the end of the one year secure period (or its extension, if such is requested), the work will be released for access worldwide.

Committee Chair

Hayes, Danie J.

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