Mineralized Electrospun Chitosan Nanofibers as Bone Scaffolds

ID：MPS/DMR/BMAT（7623）0907572 PI：Wegst，Ulrike ORG：Drexel大学名称：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资助的（公法111-5）.知识产权：该提案的总体目标是检验以下假设：通过矿化壳聚糖纤维，我们可以创造一个陶瓷-基于陶瓷相的骨替代材料，其结合了陶瓷相的强度和刚度以及通过纤维增强而增加的韧性。其目的是提供用于颅面和整形骨骼缺损的最佳修复的材料，否则将需要来自第二手术部位的骨移植物。为了验证这一假设，提出了以下研究目标：目的1：探讨一种组合的方法对散装膜的壳聚糖，甲壳素，和两者的混合物，以确定矿化的关键参数。 目的2：优化壳聚糖和甲壳素纤维毡的矿化性能。 目的3：测试未矿化和矿化壳聚糖纤维的力学性能。 目标4：通过评估人成骨细胞的粘附、铺展（形态学）和增殖并评价其功能性成骨分化，测试新型矿化壳聚糖和甲壳素膜和纤维的细胞相容性。 更具体地，提出使用壳聚糖和几丁质纤维以及羟基磷灰石（HA，Ca 10（PO 4）6（OH）2）、磷酸三钙（β-TCP，Ca 3（PO 4）2）或碳酸钙（CaCO 3）矿物来产生3-D矿化纤维复合材料，以产生足够坚固、坚硬和坚韧以替代天然骨的矿化纤维复合材料。选择甲壳素和壳聚糖作为纤维材料是因为它们具有优异的机械性能和生物相容性。壳聚糖的优点是它的可用性，多功能性和易于加工。其对于硬组织应用的缺点是当暴露于湿气时其溶胀并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。这三种矿物质，HA，β-TCP和CaCO 3被选择用于这个提议，因为它们已经成功地被用作成骨/骨诱导生物材料。更广泛的重要性：这项研究对社会有几个好处，这是由于骨替代材料的发展，模仿天然材料，它是完全融入天然骨。生物材料与骨更好的性能匹配意味着植入物可以更好地整合到天然组织中，从而产生更高的植入物。研究成果将通过校园范围的系列研讨会，在国家和国际会议上，在高质量的同行评审期刊上的出版物中广泛传播，以提高科学和技术的理解。 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群体参与研究、教学和外联活动。PI将通过与现有的德雷克塞尔项目合作，促进积极招聘和培训女性和代表性不足的少数民族工程师：德雷克塞尔星星（学生解决高级研究）本科生，SEED计划（夏季工程经验@德雷克塞尔）高中生，REU（本科生研究经验）和RET（教师研究经验）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，将在Drexel建立用于材料合成、受控环境中的微机械测试和生物相容性测试的新仪器。此外，SEM和FIB中的原位机械测试将大大增加德雷克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.