Strength and Resorption of Biodegradable Skull Implants

可生物降解颅骨植入物的强度和吸收

• 批准号: 7840513
• 负责人: David Dean
• 金额: $ 60.31万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7840513
• 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; 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; 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; 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

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）：神经外科手术和颅面重建手术后经常出现大颅骨缺陷，以进行创伤，癌症切除和先天性畸形。对植入物的美学和固定的关注，由于后手术后的需求保护了潜在的大脑免受创伤和感染的影响。已显示组织工程的骨骼置换可在骨折部位修复中骨骼骨骼缺陷，但目前，这些材料没有有效地解决足够大的颅骨缺陷，需要移植或假肢增强。 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）使用裸体大鼠肌肉内袋（即骨骨）模型来测试PPF/p-TCP，犬骨骨基构细胞和生长因子的体内相互作用； （3）选择最佳性能（即产生的骨骼的速率和强度）构造以提升到临界大小（即2.5 cm），然后选择超临界尺寸（即4.0 cm）犬颅植入物。为了实现这些目标，我们提出了以下特定目的：（1）确定CRBM和/或CMSC加载和SLA渲染的多孔PPF/P-TCP支架的有效孔几何形状和表面纹理。 (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肌内骨耳质模型。 Subaim：确定植入前生物反应器培养是否会提高骨形成的速度和质量。 （3）确定裸鼠的最佳性能骨骨策略是否会产生最初的临界大小（2.5 cm）圆形的圆形，双型，颅骨植入物中的可靠填充。在4 - 5年内，AIMS 1-3的第二个周期将使用周期I中所学的知识，以最大程度地扩大骨骼的可靠生长区域从2.5厘米或更大。与当前的护理PMMA和钛颅植入物不同，PPF/P-TCP支架中可靠的吸收和骨形成将有助于将颅腔封闭，从而使颅腔免受感染，更好地将创伤性压力转化为颅骨的其余部分，并随着时间的流逝而进行重塑。