Local Modulation of Inflammation to Heal Cranial-facial Bone Defects

描述(申请人提供)：骨缺陷会导致功能缺陷和毁容，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条件或创伤性损伤解决后才治疗的。因此，修复这些缺损处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损处。骨组织工程学在颅面和牙科领域的一个难点是软组织生长到新骨形成活跃部位的并发症。软组织植入设备从根本上阻止了进一步的骨形成。这种宿主的反应给组织工程学带来了挑战，因为任何解决方案都必须限制软组织干扰，而不会损害骨形成或诱导太多的新骨形成，从而无法实现所需的新骨的功能或美学形态。我们的目标是设计一种设备，在快速骨形成和有限的软组织干预之间取得平衡，可以扩大或修复颅面部骨缺损。在证明花生四烯酸代谢可以调节与骨形成相关的炎症之后，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内使用聚水杨酸酸酐-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设备的活性成分，将使治疗颅面部骨缺损的低成本、长保质期设备的生产成为可能。 公共卫生相关性：颅骨和其他颅面部骨骼的骨缺陷是常见的创伤和病理损伤。目前治疗颅面部骨缺损的方法与自体移植骨的第二部位并发症、使用具有潜在感染性的同种异体骨、长期疗效差、具有技术挑战性的操作和高昂的成本有关。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头面部骨缺损，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.