Mineralized Electrospun Chitosan Nanofibers as Bone Scaffolds

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ID: MPS/DMR/BMAT(7623) 0907572 PI: Wegst, Ulrike ORG: Drexel UniversityTitle: Mineralized Electrospun Chitosan Nanofibers as Bone ScaffoldsThis award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).INTELLECTUAL MERIT: The overall aim of the proposal is to test the hypothesis that by mineralizing chitosan fibers, we can create a ceramic-based bone substitute material that combines the strength and stiffness of the ceramic phase with an increased toughness through fiber reinforcement. The intention is to provide materials for optimal repair of craniofacial and orthopedic skeletal defects, which would otherwise require a bone graft from a second surgical site. To test this hypothesis the following research aims are proposed: Aim 1: To investigate a combinatorial approach on bulk films of chitosan, chitin, and a blend of the two to determine the critical parameters for mineralization. Aim 2: To optimize mineralization of chitosan and chitin fiber mats. Aim 3: To test the mechanical properties of individual non-mineralized and mineralized chitosan fibers. Aim 4: To test cytocompatibility of the novel mineralized chitosan and chitin films and fibers, by assessing adhesion, spreading (morphology), and proliferation of human osteoblasts and evaluating their functional, osteogenic differentiation. More specifically it is proposed to create a 3-D mineralized fiber composite using chitosan and chitin fibers, and hydroxyapatite (HA, Ca10(PO4)6(OH)2), tri-calcium-phosphate (beta-TCP, Ca3(PO4) 2), or calcium carbonate (CaCO3) minerals to create a mineralized fiber composite that is strong, stiff and tough enough to substitute for natural bone. The choice of chitin and chitosan as a fiber material is due to their exceptional mechanical properties and biocompatibility. The advantage of chitosan is its availability, versatility and ease in processing. Its disadvantage for hard tissue applications is that it swells when exposed to moisture and forms mechanically instable hydrogels. Chitosan fibers can be highly crosslinked and as a result are chemically and mechanically stable and better suited for hard tissue applications. The three minerals, HA, beta-TCP and CaCO3 were chosen for this proposal because they have already successfully been used as osteogenic/osteoinductive biomaterials.BROADER IMPACTS: There are several benefits of this research to society that result from the development of bone substitute materials which mimic the natural material so well that it is fully integrated into the natural bone. The better property match of biomaterial to bone means that the implant can be better integrated into natural tissue, resulting in a higher implant. Research results will be disseminated broadly through campus-wide seminar series, at national and international conferences, in publications in high quality peer-reviewed journals to enhance scientific and technological understanding. Teaching, training and learning will happen through new courses at both the graduate and undergraduate level. Every attempt will be made to involve minorities in the research, teaching, and outreach activities. The PIs will promote the active recruitment and training of women and underrepresented minorities engineers through collaboration with existing Drexel programs: Drexel STAR (Students Tackling Advanced Research) undergraduate students, SEED Program (Summer Engineering Experience @ Drexel) for high school students, REU (Research Experience for Undergraduates), and RET (Research Experience for Teachers) high school teachers. Further work will be to work with the Louis Stokes Alliance for Minority Participation (AMP) to actively recruit future lab personnel. As part of this project, new instrumentation for materials synthesis, micromechanical testing in a controlled environment, and biocompatibility testing will be established at Drexel. Additionally, in situ mechanical testing in SEM and FIB will greatly add to the central characterization facility of the Materials Science and Engineering Department at Drexel University. New experimental facilities for material testing, characterization and synthesis will be designed, built and used.