Local Modulation of Inflammation to Heal Cranial-facial Bone Defects

描述（由申请人提供）：骨缺损造成功能缺损和毁容，严重危害患者身心健康。与通常在受伤后立即治疗的骨折不同，大多数颅面骨缺损是在初始病理状况或创伤性损伤消除后治疗的。因此，治疗这些缺陷的方法必须在静止部位促进骨形成，同时禁止软组织生长到阻止骨形成的缺陷部位。颅面和牙齿区域骨组织工程的一个困难方面是软组织向内生长到新骨形成的活性部位的并发症。软组织向内生长到一个装置中，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的干扰，而不损害骨形成或诱导过多的新骨形成，从而无法实现新骨的理想功能或美学形态。我们的目标是设计一种平衡快速骨形成和有限的软组织干扰的设备，可以增强或治愈颅面骨缺陷。已经证明花生四烯酸代谢可以调节与骨形成相关的炎症，我们建议开发一种分离环加氧酶抑制（限制软组织生长）和5-脂加氧酶抑制（促进成骨细胞活性和骨形成）的装置。我们将使用水杨酸的聚（酸酐酯）（聚阿司匹林）来抑制硫酸钙载体和磷酸钙支架内的环加氧酶和5-脂加氧酶抑制剂来促进成骨。使用小分子抑制剂作为该装置的有效成分将允许生产低成本，长保质期的设备，用于治疗颅面骨缺陷。

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.