Strength and Resorption of Biodegradable Skull Implants

可生物降解颅骨植入物的强度和吸收

基本信息

批准号：
8065539
负责人：
David Dean
金额：
$ 46.42万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-02-01 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8065539
关键词：
Achievement Address Area Autologous Bioreactors Blood Platelets Brain Canis familiaris Cell Culture Techniques Cell-Matrix Junction Cephalic Clinic Complex Computer Simulation Congenital Abnormality Defect Dorsal Ensure Esthetics Excision FDA approved Fibroblast Growth Factor 2 Fracture Fumarates Goals Growth Factor Health Implant In Vitro Infection Intramuscular Lead Learning Malignant Neoplasms Mechanics Meninges Modeling Muscle Nude Rats Operative Surgical Procedures Osteogenesis Patients Polymethyl Methacrylate Polypropylenes Postoperative Period Property Prosthesis Reconstructive Surgical Procedures Reliance Research Personnel Rest Scalp structure Site Stress Stretching Surface Surgical Flaps Technology Testing Texture Time Tissue Engineering Tissues Titania Titanium Translating Translations Trauma Vascular Endothelial Growth Factors bone bone morphogenetic protein 2 bone morphogenetic protein 7 bone strength cell growth craniofacial cranium design implantation improved in vivo neurosurgery osteogenic osteoprogenitor cell preimplantation programs repaired sample fixation scaffold seal skeletal skull implant standard of care tricalcium phosphate

项目摘要

DESCRIPTION (provided by applicant): Large skull defects arise frequently following neurosurgery and craniofacial reconstructive surgery for trauma, cancer resection, and congenital deformity. Concerns over revascularization, aesthetics and fixation of the implant are magnified by the post-surgical need to protect the underlying brain from both trauma and infection. Tissue engineered bone replacements have been shown to ossify small skeletal defects with potential utility in fracture site repair, but currently, these materials do not effectively address skull defects large enough to require graft or prosthetic augmentation. We propose to: (1) use Stereolithographic (SLA) rendering (i.e., rapid prototyping) of polypropylene fumarate)/p-tricalcium phosphate (PPF/p-TCP) to produce porous implants with computer-modeled mechanical, geometric, cell attachment (i.e., in vitro in a bioreactor, or in vivo), and resorption properties; (2) use a nude rat intra-muscular pocket (i.e., bone ossicle) model to test the in vivo interaction of PPF/p-TCP, canine osteoprogenitor cells, and growth factors; (3) select the best performing (i.e., rate and strength of bone produced) construct to elevate to a critical size (i.e., 2.5 cm) and then a super-critical size (i.e., 4.0 cm) canine cranial implant. In order to accomplish these goals we propose the following specific aims: (1) Determine an effective pore geometry and surface texture for cRBM and/or cMSC loading and seeding of SLA-rendered, porous PPF/p-TCP scaffolds. (2) Determine the most osteogenic combination of the best AIM 1 scaffolds (i.e., PPF geometry, PPF texture, cRBM, or cMSCs), bioreactor or in vivo cell culture, and autologous (platelets, cRBM) and/or exogenous (TGF-P2, BMP-2, BMP-7, FGF-2 and VEGF) growth factors in a nude rat intra-muscular bone ossicle model. Subaim: Determine whether pre-implantation bioreactor culturing improves rate and quality of bone formation. (3) Determine whether the best performing bone ossicle strategy for the nude rat produces reliable infilling of initially critical size (2.5 cm) circular, biparietal, cranial implants in the dog. A second cycle of Aims 1-3 in years 4-5 will use what is learned in Cycle I to maximally expand the area of reliably grown bone from 2.5 to 4.0 cm or larger. Unlike current standard of care PMMA and titanium cranial implants, reliable resorption and bone formation in PPF/p-TCP scaffolds will serve to seal off the cranial cavity from infection, better translate traumatic stress to the rest of the skull, and remodel with the rest of the skull over time.

描述（由申请人提供）：在因创伤、癌症切除和先天性畸形而进行的神经外科和颅面重建手术后，经常会出现大的颅骨缺损。由于术后需要保护底层大脑免受创伤和感染，人们对植入物的血运重建、美观和固定的担忧更加严重。组织工程骨替代物已被证明可以使小的骨骼缺陷骨化，在骨折部位修复中具有潜在的用途，但目前，这些材料不能有效地解决大到需要移植或假体增强的颅骨缺陷。我们建议：（1）使用富马酸聚丙烯/对磷酸三钙（PPF/p-TCP）的立体光刻（SLA）渲染（即快速原型制作）来生产具有计算机建模的机械、几何、细胞附着的多孔植入物（即，在生物反应器中的体外，或体内），以及再吸收特性； (2)利用裸鼠肌内袋(即骨小骨)模型测试PPF/p-TCP、犬骨祖细胞和生长因子的体内相互作用； (3) 选择性能最佳（即骨生成率和强度）的构造，以提升至临界尺寸（即 2.5 厘米），然后提升至超临界尺寸（即 4.0 厘米）犬颅骨植入物。为了实现这些目标，我们提出以下具体目标：（1）确定 cRBM 和/或 cMSC 加载和 SLA 渲染的多孔 PPF/p-TCP 支架接种的有效孔隙几何形状和表面纹理。 (2) 确定最佳 AIM 1 支架（即 PPF 几何结构、PPF 纹理、cRBM 或 cMSC）、生物反应器或体内细胞培养物以及自体（血小板、cRBM）和/或外源（TGF-β）的最具成骨性的组合。 P2、BMP-2、BMP-7、FGF-2 和 VEGF) 裸鼠肌内骨小骨模型中的生长因子。 Subaim：确定植入前生物反应器培养是否可以提高骨形成的速度和质量。 (3) 确定裸鼠的最佳骨小骨策略是否能在狗体内产生最初临界尺寸（2.5 厘米）圆形双顶颅骨植入物的可靠填充。第 4-5 年目标 1-3 的第二个周期将利用周期 I 中学到的知识，最大限度地将可靠生长的骨骼面积从 2.5 扩大到 4.0 厘米或更大。与目前的护理标准 PMMA 和钛颅骨植入物不同，PPF/p-TCP 支架中可靠的吸收和骨形成将有助于密封颅腔免受感染，更好地将创伤应力转移到颅骨的其余部分，并与其余部分一起重塑随着时间的推移头骨。