Diversity Supplement to Tissue Engineering Strategies to Revitalize Allografts

摘要： 这份多样性副刊的目标是培训桑德拉·卡斯蒂略·阿吉雷。具体地说，她的训练将 将通过拟议的研究计划进行。这项工作的重点是用于骨再生的纳米材料， 特别是为了促进同种异体骨移植的振兴。延迟愈合或不愈合，移植物重塑和 修复和代谢性骨骼疾病提出了迫切需要开发新技术来增强 骨骼愈合。虽然最近的数据表明Wnt信号对出生后骨再生是必不可少的， 由于持续时间较短，用于支持或增强这些内源性机制的Wnt激动剂的传递受到限制 动作和偏离目标的效果。因此，在开发特定的药物输送方面存在着关键的技术差距 骨祖细胞调节骨再生过程的方法。因此，这项工作寻求发展 骨选择性纳米材料控制Wnt激动剂的释放和促进骨再生 同种异体骨移植修复大块骨缺损。我们在这个计划中的目标是(1)建立 靶向重建的同种异体骨移植的聚合物纳米治疗要求，(2)确定所需的 骨再生药物的剂量和寿命，以实现细胞募集和骨再生 体外，以及(3)建立药物输送系统在临界大小的骨缺损中的再生效率。我们 假设可以通过靶向聚合物实现骨再生的吸收部位特异性刺激 骨合成代谢Wnt激动剂的治疗性递送。这项工作的基本原理是确定可翻译的 选择性输送骨合成新陈代谢药物以促进骨再生的疗法。这一点的长期影响 工作是开发高效率和特异性的针对骨的药物的聚合物纳米疗法 促进骨移植愈合并严格培训在骨移植领域代表不足的少数族裔研究人员 治疗性生物材料和骨科研究。

Abstract: The goal of this Diversity supplement is the training of Sandra Castillo Aguirre. Specifically, her training will be undertaken via the research plan proposed. The work focuses on nanomaterials for bone regeneration, specifically to enhance the revitalization of bone allografts. Delayed union or nonunion, graft remodeling and repair, and metabolic bone diseases present critical needs for development of new technologies to enhance skeletal healing. While recent data reveal that Wnt signaling is essential for postnatal bone regeneration, delivery of Wnt agonists to support or enhance these endogenous mechanisms are limited due to short duration of action and off-target effects. Thus, a critical technological gap exists in developing specific drug delivery approaches for osteoprogenitors to modulate bone regenerative processes. Therefore, this work seeks to develop bone-selective nanomaterials designed to control Wnt agonist delivery and enhance bone regeneration in allograft-mediated reconstruction of massive bone defects. Our objective within this program is to (1) establish polymer nanotherapeutic requirements for targeting of remodeling bone allografts, (2) determine the required dose and longevity of osteoregenerative drug delivery to achieve cellular recruitment and bone regeneration in vitro, and (3) establish the regenerative efficacy of the drug delivery system in critical-sized bone defects. We hypothesize that resorption site-specific stimulation of bone regeneration can be achieved via targeted polymer therapeutic delivery of osteoanabolic Wnt agonists. The rationale for this work is to identify translatable therapies to selectively deliver osteoanabolic drugs to enhance bone regeneration. The long-term impact of this work is the development of polymer nanotherapeutics to target drugs to bone with high efficacy and specificity to promote bone graft healing and to rigorously train an underrepresented minority researcher in the field of therapeutic biomaterials and orthopaedic research.