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Studies in cranial suture biology

Premaraj, Sundaralingam
http://rave.ohiolink.edu/etdc/view?acc_num=osu1155140476

Abstract Details

2006, Doctor of Philosophy, Ohio State University, Oral Biology.
Craniosynostosis is a disorder characterized by premature fusion of cranial sutures. Treatment of prematurely fused sutures typically involves a series of invasive surgical procedures beginning in infancy. In many cases, surgical sites show rapid resynostosis. Quantifying gene expression patterns in cranial sutures is essential for the design of targeted adjunct therapies for craniosynostosis. Using real time RT-PCR in a rodent model of cranial suture biology, expression profiles of several growth factor ligands and receptors were quantitatively characterized. Administration of cytokines or genes that correct the underlying pathological process may arrest the ossification process. Exogenous application of transforming growth factor-beta3 cytokine has been shown to inhibit suture fusion. However, use of cytokines as localized therapeutic agents is limited by the lack of a satisfactory delivery system. Release kinetics and bioactivity of a simplified cytokine/collagen gel system designed to achieve extended, local delivery of bioactive cytokines at sites of premature cranial suture fusion were investigated. Delivery of cytokines is limited by short half-life, degradation of the proteins during incorporation or following the release from the vehicle by temperature, or change in chemical environment. Gene transfer can avoid some of these limitations. Therefore, suitability of a dense collagen gel as a vehicle for sustained delivery of non-viral plasmid DNA to sutural tissues was investigated. Structural integrity, bioactivity and transfectivity of released plasmids were established in rat osteoblast and calvarial organ cultures. Data revealed collagen gel can provide sustained release of plasmid DNA. The plasmid DNA retained its transfectivity as demonstrated by the prolonged osteoblast transfection and elevated growth factor production. The ability to rescue cranial suture fusion by released Tgf-beta3 plasmid was tested in vitro and in vivo. Data from in vitro studies demonstrated that Tgf-beta3 plasmid treated group was found to have 77% to 85% less bony bridging than collagen control and untreated groups. Similarly in animals treated with Tgf-beta3 plasmid, there was a significant reduction in suture fusion in the middle region of the posterior frontal sutures when compared to control groups. In this region Tgf-beta3 plasmid treated group was found to have 70% to75% less bony bridging than control groups.
Sarandeep Huja (Advisor)
170 p.
craniosynostosis; cranial sutures; collagen gel; non-viral plasmid; Tgf-beta3

Recommended Citations

Citations

  • Premaraj, S. (2006). Studies in cranial suture biology [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1155140476

    APA Style (7th edition)

  • Premaraj, Sundaralingam. Studies in cranial suture biology. 2006. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1155140476.

    MLA Style (8th edition)

  • Premaraj, Sundaralingam. "Studies in cranial suture biology." Doctoral dissertation, Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=osu1155140476

    Chicago Manual of Style (17th edition)

osu1155140476
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© 2006, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.