Layered Manufacture of Bioactive Porous TE Scaffolds

描述（由申请人提供）：在美国一般人群中，每年约有275，000例骨骼缺损需要植骨手术才能实现愈合。此外，有必要向越来越多的士兵和海军陆战队员提供护理，他们因炸弹爆炸、弹药、严重福尔斯摔倒和车辆事故而头部严重受伤。本提案中描述的研究针对修复临界尺寸颅骨缺损的临床问题。关键尺寸的颅骨缺损通常是由于原发性和转移性肿瘤切除导致的骨丢失、骨骼创伤后的骨丢失或先天性畸形导致的骨丢失。最终的手术目标是通过植入功能性的、可生物降解的、生物相容的、生物活性的支架来修复缺损，该支架将促进骨再生并随着时间的推移与宿主骨完全整合。本研究的总体目标是开发精确制造定制设计的聚丙烯富马酸酯（PPF）多孔支架的方法，该支架适用于骨再生，并通过在大鼠骨髓基质细胞（MSC）和成骨补充培养基存在下在灌注生物反应器中培养使这些支架具有生物活性。为了实现这一目标，本项目将分为三个具体目标：1）设计和制造一个能够灌注定制多孔支架的灌注生物反应器; 2）使用分层制造技术立体光刻（SL）在生物相容性聚合物PPF中设计和制造适用于骨再生的多孔支架;和3）使PPF多孔支架具有生物活性。本研究的第一部分将集中于具有适合于定制设计支架的位置的可互换盒的灌注生物反应器的设计和制造。PPF将按照先前公布的程序合成，分子量为800 - 1，000 Da和1，800 - 2，000 Da。三维CAD将用于设计定制的多孔支架，其具有精确控制的外部和内部高度多孔的互连结构。支架将使用立体光刻法制造，用大鼠MSC接种，并在灌注生物反应器中孵育4、8和12天。生物活性的程度将通过ELISA蛋白质测定和钙沉积的程度来确定。这项研究将开发制造和生物学策略，以生产生物活性的患者特异性支架，用于修复颌面骨缺损。

DESCRIPTION (provided by applicant): There are approximately 275,000 skeletal defects a year reported in the U.S. general population that require bone graft procedures to achieve union. In addition, there is a need to provide care to the increasing number of soldiers and Marines suffering from critical head injuries caused by bomb blasts, munitions, serious falls and vehicle accidents to those engaged in the Iraq conflict. The research described in this proposal is directed towards this clinical problem of repairing critical-sized cranial defects. Critical sized cranial defects are often the result of bone loss due to the removal of primary and metastatic tumors, bone loss after skeletal trauma, or as a result of congenital deformity. The ultimate surgical goal is to repair the defect by implantation of a functional, biodegradable, biocompatible, bioactive scaffold that will illicit bone regeneration and over time fully integrate with the host bone. The overall goal of this research is to develop methods to accurately fabricate custom-designed polypropylene fumarate) (PPF) porous scaffolds suitable for bone regeneration and render those scaffolds bioactive by culturing in a perfusion bioreactor in the presence of rat marrow stromal cells (MSCs) and osteogenic supplemented media. To accomplish this goal, this project will be divided into three specific aims: 1) design and manufacture a perfusion bioreactor capable of perfusing custom porous scaffolds; 2) design and manufacture porous scaffolds suitable for bone regeneration in the biocompatible polymer PPF using the layered manufacturing technology stereolithography (SL); and 3) render the PPF porous scaffolds bioactive.The first section of this study will focus on the design and manufacture of a perfusion bioreactor with interchangeable cassettes suitable for the location of custom designed scaffolds. PPF will be synthesized with molecular weights of 800-1,000 Da and 1,800-2,000 Da following previously published procedures. Three-dimensional CAD will be used to design custom porous scaffolds with accurately controlled external and internal highly porous, interconnected architecture. Scaffolds will be manufactured using stereolithography, seeded with rat MSCs, and incubated in perfusion bioreactors for 4, 8 and 12 days. The degree of bioactivity will be determined by ELISA protein assays, and degree of calcium deposition. This research will develop manufacturing and biological strategies to produce bioactive patient-specific scaffolds for the repair of maxiliofacial bone defects.