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Development of an injectable, in situ crosslinkable, degradable polymeric carrier for osteogenic cell populations
Payne, Richard Grady
Doctor of Philosophy
An injectable, in situ crosslinkable, degradable polymeric carrier for osteogenic cell populations was developed. Specifically, a system for encapsulating marrow stromal osteoblasts in gelatin microspheres has been implemented with the goal of incorporation into a crosslinking composite based on poly(propylene fumarate) (PPF). Initially, the microparticle formation procedure was evaluated for effects on the marrow stromal cells. It was determined that the encapsulation procedure had only minor effects on the viability, proliferation, and phenotypic expression through 28 days. The surfaces of the microparticles were treated to provide mechanical integrity at body temperature. The gelatin microparticles were exposed to two levels of a crosslinker in order to assess the effect of crosslinker concentration on cell viability, proliferation, and phenotypic expression. The results indicated that exposure to a relatively high concentration of the crosslinker (5 mM) for a relatively short amount of time (5 min) produced microparticles which maintained their mechanical integrity in 37°C media for about one hour before dispersing. It yielded only minor reductions in the measured properties over 28 days. Physical properties of the crosslinked microspheres were measured. Based on these observations, it was concluded that the encapsulation procedure we had developed was a candidate for use with the crosslinking PPF composite in the next study. Cells encapsulated in crosslinked microparticles were placed on fully crosslinked PPF composites and on composites in various stages of crosslinking. The results showed that encapsulated cells retained their viability and proliferation to a much greater extent than nonencapsulated cells when placed on crosslinking substrates. A final study was performed using one of the crosslinking composite addition times, and varying the formulation of the composites by adjusting the polymer to monomer ratio. The results of this 28 day experiment indicated that encapsulation of cells allowed them to remain viable and express the osteoblastic phenotype when placed on crosslinking PPF based composites. Nonencapsulated cells, however, did not retain their viability on those same crosslinking substrates. The outcome of this work is that the resulting polymeric cell delivery system, which is injectable and in situ crosslinkable, holds promise for bone regeneration and orthopaedic tissue engineering.
Biomedical engineering; Chemical engineering