PFI:AIR - TT: Scale-up and Prototyping of Novel Scaffold Fabrication for Bone Regeneration

该PFI：AIR技术翻译项目专注于翻译仿生胶原基骨移植支架，用于增强骨缺损修复和新骨再生。 目前，美国每年进行超过130万例骨修复手术，其中很大一部分用于大面积缺损修复。 该项目将产生支架生产的原型，并启动仿生支架的FDA文件编制过程。 仿生支架将直接解决目前市场上大多数现有骨移植材料的问题，包括骨传导性差、机械性能差以及与天然骨再生速率不同的降解速率。 与该市场领域的领先产品相比，其已证明骨形成能力增强。这种新型骨替代材料将极大地造福于因意外或疾病造成骨缺损，需要进行骨科手术的患者。 该产品的商业化将大大提高患者的生活质量，缩短康复时间，并大大降低与住院和医疗保健相关的医疗费用。仿生支架具有以下独特的功能，使其成为骨移植市场上具有竞争力的产品：（1）可调的微观和宏观结构，适合于增强血管化，骨祖细胞迁移和新骨形成;（2）温和的制造条件（3）上级的机械性能，在新骨形成之前为初始手术处理和机械支撑提供必要的机械强度;（4）与常用的等轴支架和商业支架相比，具有优异的骨传导性，这将显著减少患者的康复时间;（5）与新骨长入速度相匹配的降解速度，可通过天然骨完美修复缺损，优于市面上任何人工骨替代材料的上级性能。本项目在从研究发现向商业应用转化的过程中，填补了以下技术空白。它将集中在与仿生支架放大和原型相关的问题，如大块支架的不均匀性和不可重复性。为了解决这些问题，将进行热流分析，并建立一个严密的控制系统，这将进一步促进理解支架结构/性能和支架放大和原型制作中的工艺参数之间的相互关系。该项目将由一名材料科学家领导，由两位企业家指导商业化，并由一名整形外科医生提供建议，为团队提供最终用户的观点。此外，它将导致一些研究生和本科生在生物材料规模扩大，产品原型，FDA文件和产品商业化领域的培训，同时使他们接触到多学科的工作环境。

This PFI: AIR Technology Translation project focuses on translating a biomimetic collagen-based bone grafting scaffold for enhanced bone defect repair and new bone regeneration. Currently, more than 1.3 million bone-repair procedures are performed annually in the USA, and a large proportion of them are for large defect repair. The project will result in a prototype of the scaffold production as well as initiation of the FDA documentation process of the biomimetic scaffold. The biomimetic scaffold will directly address the problems of most currently existing bone grafting materials on the market, including poor osteoconductivity, poor mechanical properties, and dissimilar degradation rates to natural bone regenerating rates. It has demonstrated enhanced bone forming capability when compared to a leading product in this market space. The new bone substitute material will greatly benefit patients who suffer from bone defects caused by accidents or diseases, and are in need of orthopedic surgery. Commercialization of this product will greatly improve quality of life for patients, shorten rehabilitation time, and substantially lower medical costs associated with hospitalization and health care.The biomimetic scaffold has the following unique features which make it a competitive product in the bone grafting market: (1) Tunable micro- and macro-structure suitable for enhanced vascularization, osteoprogenitor cells migration, and new bone formation; (2) Mild fabrication conditions (room temperature and neutral pH) and simple fabrication process, which makes the scale-up manufacturing step easy to achieve at a low cost; (3) Superior mechanical properties, providing the necessary mechanical strength for initial surgical handling and mechanical support prior to new bone formation; (4) Excellent osteoconductivity compared to both a commonly used equiaxed scaffold and a commercial scaffold, which will significantly reduce patients' rehabilitation time; (5) Degradation rate matching the ingrowth rate of new bone, leading to perfect defect repair by natural bone that is superior to any artificial bone substitute materials on the market.This project addresses the following technology gaps as it translates from research discovery toward commercial application. It will center on issues related to the biomimetic scaffold scale-up and prototype, such as inhomogeneity and irreproducibility of large pieces of scaffold. To address these problems, heat flow analyses will be conducted and a tight control system will be established, which will further advance understanding of the interrelationship between scaffold structure/property and processing parameters in scaffold scale-up and prototyping. The project will be led by a materials scientist, guided by two entrepreneurs for commercialization, and advised by an orthopedic surgeon to provide the team the end-user perspective. In addition, it will result in the training of a number of graduate and undergraduate students in areas of biomaterial scale-up, product prototyping, FDA documentation and product commercialization, while exposing them to a multidisciplinary working environment.