Local Modulation of Inflammation to Heal Cranial-facial Bone Defects

局部调节炎症来治愈颅面骨缺损

基本信息

批准号：
8079511
负责人：
J Patrick O'Connor
金额：
$ 62.16万
依托单位：
UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-17 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8079511
关键词：
Active Sites Address Anhydrides Anti-Inflammatory Agents Anti-inflammatory Appearance Arachidonate 5-Lipoxygenase Arachidonic Acids Area Autologous Transplantation Becaplermin Biocompatible Materials Bone Regeneration Bone Tissue Calcium Sulfate Cephalic Characteristics Clinical Custom Data Defect Dental Device or Instrument Development Devices Dose Drug Delivery Systems Engineering Equilibrium Esters Esthetics Face Fracture Goals Growth Growth Factor Harvest Healed Homeostasis Hydroxyapatites Immune response In Vitro Individual Inflammation Inflammatory Inflammatory Response Injury Life Lipoxygenase Inhibitors Measures Mental Health Metabolism Methods Modeling Morbidity - disease rate Morphology Nature Osteoblasts Osteogenesis Pathway interactions Patients Procedures Production Prostaglandin-Endoperoxide Synthase Qualifying Reaction Regulation Resolution Salicylic Acids Site Solutions Testing Time Tissue Engineering allogenic bone transplantation base bone calcium phosphate cost craniofacial craniofacial repair cranium efficacy testing face bone structure functional restoration healing implantation inhibitor/antagonist iterative design meetings new technology osteogenic physical conditioning pre-clinical public health relevance recombinant human bone morphogenetic protein-2 response scaffold small molecule soft tissue tricalcium phosphate

项目摘要

DESCRIPTION (provided by applicant): Bone defects cause functional deficits as well as disfigurement that can severely harm the patients' physical and psychological health. Unlike bone fractures that are usually treated immediately after injury, most cranial-facial bone defects are treated after the initial pathological condition or traumatic injury has been resolved. Thus, methods to heal these defects must promote bone formation at a quiescent site while prohibiting growth of soft tissues into the defect site that stop bone formation. One difficult aspect of bone tissue engineering in the craniofacial and dental areas is complications from soft tissue ingrowth into the active site of new bone formation. Soft tissue ingrowth into a device essentially halts further bone formation. This host response creates a challenge for tissue engineering in that any solution must limit soft tissue interference without impairing bone formation or inducing so much new bone formation that the desired functional or aesthetic morphology of the new bone is not achieved. Our goal is to engineer a device that balances rapid bone formation with limited soft tissue interference that can augment or heal cranial-facial bone defects. Having shown that arachidonic acid metabolism can modulate inflammation related to bone formation, we propose to develop a device that separates cyclooxygenase inhibition (limits soft tissue growth) from 5-lipoxygenase inhibition (promotes osteoblast activity and bone formation). We will use a poly (anhydride-ester) of salicylic acid (PolyAspirin) to inhibit cyclooxygenase and a 5-lipoxygenase inhibitor within a calcium sulfate carrier and calcium phosphate scaffold to promote osteogenesis. The use of small molecule inhibitors as the active ingredients of this device will allow production of low-cost, long shelf-life devices for treating cranial-facial bone defects. PUBLIC HEALTH RELEVANCE: Bony defects of the skull and other cranial-facial bones are common traumatic and pathological injuries. Current methods to treat cranial-facial bone defects are associated with second-site morbidity from autograft harvest, use of potentially infectious allograft bone, poor long-term efficacy, technically challenging procedures, and high costs. Our goal is to develop a low-cost, easy to use and store, tissue engineering device to treat cranial-facial bone defects that accelerates healing by modulating the host inflammatory response.

描述（由申请人提供）：骨缺陷会导致功能缺陷以及毁容，严重损害患者的身心健康。与通常在受伤后立即治疗的骨折不同，大多数颅面部骨缺损是在最初的病理状况或创伤性损伤解决后才进行治疗。因此，治愈这些缺陷的方法必须促进静止部位的骨形成，同时阻止软组织生长到阻止骨形成的缺陷部位。颅面和牙科区域骨组织工程的一个难题是软组织向内生长到新骨形成活性部位的并发症。软组织向内生长基本上阻止了进一步的骨形成。这种宿主反应给组织工程带来了挑战，因为任何解决方案都必须限制软组织干扰，而不损害骨形成或诱导大量新骨形成，以致无法实现新骨所需的功能或美观形态。我们的目标是设计一种能够平衡快速骨形成与有限软组织干扰的设备，从而增强或治愈颅面部骨缺损。已经证明花生四烯酸代谢可以调节与骨形成相关的炎症，我们建议开发一种装置，将环氧合酶抑制（限制软组织生长）与5-脂氧合酶抑制（促进成骨细胞活性和骨形成）分开。我们将在硫酸钙载体和磷酸钙支架中使用水杨酸聚（酸酐酯）（聚阿司匹林）来抑制环氧合酶和 5-脂氧合酶抑制剂，以促进成骨。使用小分子抑制剂作为该装置的活性成分将可以生产低成本、长保质期的装置，用于治疗颅面骨缺损。公共卫生相关性：颅骨和其他颅面骨的骨缺损是常见的创伤性和病理性损伤。目前治疗颅面骨缺损的方法与自体移植物收获、使用潜在感染性同种异体移植骨的第二部位发病率、长期疗效差、技术上具有挑战性的手术和高成本有关。我们的目标是开发一种低成本、易于使用和存储的组织工程设备来治疗颅面骨缺损，通过调节宿主炎症反应来加速愈合。