Local Modulation of Inflammation to Heal Cranial-facial Bone Defects

局部调节炎症来治愈颅面骨缺损

• 批准号: 7872791
• 负责人: J Patrick O'Connor
• 金额: $ 62.83万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 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/7872791
• 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; pre-clinical; public health relevance; recombinant human bone morphogenetic protein-2; response; scaffold; small molecule; soft tissue; tricalcium phosphate

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）：骨骼缺陷会导致功能不足以及可能严重损害患者身体和心理健康的毁容。与通常在受伤后立即治疗的骨骨折不同，在最初的病理状况或创伤性损伤已经解决后，大多数颅面骨缺损得到治疗。因此，治愈这些缺陷的方法必须在静止部位促进骨骼形成，同时禁止软组织在阻止骨形成的缺陷部位生长。颅面和牙科区域中骨组织工程的一个困难方面是从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停止了进一步的骨形成。该宿主反应对组织工程产生了挑战，即任何解决方案都必须限制软组织干扰而不会损害骨骼形成或诱导如此多的新骨形成，以至于无法实现新骨的所需功能或美学形态。我们的目标是设计一种可以平衡快速骨形成与有限的软组织干扰的装置，该装置可以增加或治愈颅面骨缺损。在表明蛛网膜酸代谢可以调节与骨形成有关的炎症，我们建议开发一种将环氧酶抑制（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）的装置。我们将使用水杨酸（多重毒素）的聚（酸酐）来抑制硫酸钙载体和磷酸钙支架内的环氧合酶和5-脂氧合酶抑制剂以促进肌动灭发生。将小分子抑制剂用作该设备的活性成分，将允许生产低成本，长期的保质期设备来治疗颅 - 骨缺损。 公共卫生相关性：头骨和其他颅面骨骼的骨缺陷是常见的创伤和病理损伤。当前治疗颅骨缺损的方法与自体移植收获，潜在感染性同种异体移植骨，长期疗效，技术挑战性程序和高成本相关。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装置，以治疗颅面骨缺损，通过调节宿主炎症反应来加速愈合。