Local Modulation of Inflammation to Heal Cranial-facial Bone Defects

描述（由申请人提供）：骨缺损导致功能缺陷以及严重损害患者身心健康的毁容。与通常在受伤后立即治疗的骨折不同，大多数颅面骨缺损在初始病理状态或创伤性损伤得到解决后进行治疗。因此，治愈这些缺损的方法必须促进静止部位的骨形成，同时禁止软组织生长到停止骨形成的缺损部位。骨组织工程在颅面和牙齿领域的一个困难方面是软组织长入新骨形成的活性部位的并发症。软组织长入器械基本上阻止了进一步的骨形成。这种宿主反应对组织工程产生了挑战，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如此多的新骨形成，以至于不能实现新骨的期望功能或美学形态。我们的目标是设计一种能够平衡快速骨形成和有限软组织干扰的装置，以增强或愈合颅面骨缺损。已经表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。我们将使用水杨酸的聚（腺苷酸酯）（聚阿司匹林）来抑制环氧合酶，并在硫酸钙载体和磷酸钙支架内使用5-脂氧合酶抑制剂来促进骨生成。使用小分子抑制剂作为该装置的活性成分将允许生产用于治疗颅面骨缺损的低成本、长保质期装置。 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的第二部位发病率、使用潜在感染性同种异体骨、长期疗效差、技术上具有挑战性的手术和高成本相关。我们的目标是开发一种低成本、易于使用和储存的组织工程装置来治疗颅面骨缺损，通过调节宿主的炎症反应来加速愈合。

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.