Mineralized Electrospun Chitosan Nanofibers as Bone Scaffolds

ID: MPS/DMR/BMAT(7623) 0907572 PI: Wegst， Ulrike ORG: Drexel university标题：矿化电纺壳聚糖纳米纤维作为骨支架该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。智力优势：该提案的总体目标是测试假设，即通过矿化壳聚糖纤维，我们可以创造出一种陶瓷基骨替代材料，该材料结合了陶瓷相的强度和刚度，并通过纤维增强增强了韧性。目的是为颅面和骨科骨骼缺损的最佳修复提供材料，否则需要从第二个手术部位移植骨。为了验证这一假设，提出了以下研究目标：目的1：研究壳聚糖、甲壳素和两者混合物的大块膜的组合方法，以确定矿化的关键参数。目的2：优化壳聚糖和几丁质纤维垫矿化工艺。目的3：测试非矿化和矿化壳聚糖纤维的力学性能。目的4：通过评估人成骨细胞的粘附、扩散（形态）和增殖，以及评估其功能和成骨分化，来测试新型矿化壳聚糖和几丁质薄膜和纤维的细胞相容性。更具体地说，有人建议使用壳聚糖和几丁质纤维、羟基磷灰石(HA, Ca10（PO4)6(OH)2）、三磷酸钙（β - tcp, Ca3(PO4) 2）或碳酸钙（CaCO3）矿物质来制造一种3-D矿化纤维复合材料，这种纤维复合材料坚固、坚硬，足以替代天然骨骼。选择几丁质和壳聚糖作为纤维材料是由于它们卓越的机械性能和生物相容性。壳聚糖的优点是可用性好、用途广泛、易于加工。它的缺点是硬组织应用时，它膨胀时暴露于水分和形成机械不稳定的水凝胶。壳聚糖纤维可以高度交联，因此具有化学和机械稳定性，更适合硬组织应用。我们之所以选择HA、β - tcp和CaCO3这三种矿物质，是因为它们已经被成功地用作成骨/骨诱导生物材料。更广泛的影响：由于骨替代材料的发展，这项研究对社会有几个好处，这些材料很好地模仿了天然材料，使其完全融入天然骨骼。生物材料与骨的性能更好的匹配意味着种植体可以更好的融入自然组织，从而获得更高的种植体。研究成果将通过全校范围的系列研讨会、国内和国际会议、高质量的同行评审期刊的出版物广泛传播，以增进对科学和技术的了解。教学、培训和学习将通过研究生和本科生的新课程进行。将尽一切努力让少数民族参与研究、教学和外展活动。pi将通过与Drexel现有项目的合作，促进积极招聘和培训女性和未被充分代表的少数族裔工程师：Drexel STAR（学生进行高级研究）本科生，SEED项目（高中生暑期工程体验），REU（本科生研究体验）和RET（教师研究体验）高中教师。进一步的工作将是与路易斯·斯托克斯少数民族参与联盟（AMP）合作，积极招募未来的实验室人员。作为该项目的一部分，Drexel将建立新的材料合成仪器、受控环境下的微力学测试和生物相容性测试。此外，在SEM和FIB的现场机械测试将大大增加德雷塞尔大学材料科学与工程系的中心表征设施。将设计、建造和使用用于材料测试、表征和合成的新实验设施。

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.