Mobile Porous Subdermal Barrier to Maintain the Skin Seal of Percutaneous Devices

描述（由申请人提供）：改良的假肢接口以改善康复将外植体直接附着于骨锚定，经皮通过皮肤的骨整合植入物上，被认为是用于肢体丧失个体的普通插座型技术的替代方案。经皮骨整合种植体的主要失效模式之一是在皮肤-种植体界面处发生感染。因此，骨整合假体作为一种潜在的临床治疗方法的成功在很大程度上依赖于在该界面建立皮肤密封以保持感染的自然屏障。在这项技术能够安全地引入美国之前，这是一个必须解决的重大挑战。值得注意的是，我们目前的研究表明，皮下多孔涂层屏障最初可以附着在皮肤上，并防止感染长达9个月。该数据还表明，皮肤迁移在经皮后周以1.6 ~ 0.5 mm/月的速度成为一种常见现象。此外，皮肤植入物界面的组织学检查显示，邻近经皮支架的上皮网状嵴变平，并因缺乏下层血管化的乳头状真皮而失活。愈合伤口周围上皮变平是一种正常现象，但在我们的研究中，即使在术后6个月后，仍持续存在变平的网状嵴，这在临床上仍然值得关注。这些观察结果表明伤口愈合受损，这可能是观察到皮肤沿皮下屏障迁移的可能原因。据认为，造成这种现象的原因之一是由于非生理性的区域应变场导致血液供应不足。皮肤组织的生理微机械力已被证明可以建立局部应力-应变场。皮肤缺损引起的生理应变场的变化通过促进细胞增殖、上皮细胞的迁移和血管生成来刺激伤口愈合。因此，我们假设，为了在皮肤-植入物界面处维持健康的皮肤组织屏障，需要维持皮肤组织的局部应变场。本研究计划的主要目标是开发和验证可移动的多孔涂层真皮屏障的功效，以维持自然应变场，并赋予经皮骨整合植入物稳定的无感染皮肤附着。因此，需要测试的主要假设是，通过允许皮肤在多孔涂层皮下屏障附近保持生理应变场，可以维持皮肤密封并防止皮肤迁移。在目标1中，将设计和制造具有动态、多孔涂层的皮下磁盘的经皮植入物，以维持皮肤的局部生理运动。使用猪模型，感染率将与对照组（静态皮下圆盘）进行比较。在目标2(a)和2(b)中，动态、多孔涂层皮下磁盘组维持皮肤密封并随后阻止皮肤迁移的能力将在组织学和生物力学上进行测量，在3个月和6个月的时间周期内进行临床评估，并与对照组进行比较。为失去一条肢体的病人更换假体所需的终生保健费用预计约为50万美元。随着无感染骨整合假肢技术的建立，可以显著降低医疗成本，极大地改善170万截肢者的生活。

DESCRIPTION (provided by applicant): Improved interfaces for prostheses to improve rehabilitation Attaching exo-prostheses directly to bone-anchored, osseointegrated implants that pass percutaneously through the skin is being considered as an alternative to common socket-type technologies for individuals with limb loss. One of the primary failure modes of load bearing, percutaneous osseointegrated implants is the development of infection at the skin-implant interface. Thus, the success of osseointegrated prostheses as a potential clinical treatment relies heavily on establishing a skin seal to maintain a natural barrier to infection at this interface. This is a major challenge that must be addressed before this technology can be safely introduced into the United States. Notably, our current research studies have shown that a subdermal, porous coated barrier can initially attach to the skin and prevent infection for up to nine months. This data also shows that skin migration becomes a common occurrence at the periphery of the percutaneous post at a rate of 1.6¿0.5 mm/month. Moreover, histological examination of the skin-implant interface revealed that the epithelial rete ridges adjacent to the percutaneous post were flattened and devitalized with the absence of an underlying vascularized papillary dermis. The epithelial flattening around a healing wound is a normal event, but persistent presence of flattened rete ridges, even after a post operative period of 6 months as seen in our studies, remains clinically concerning. These observations indicate impaired wound healing, which may be the probable reason for the observed skin migration along the subdermal barrier. It is believed that one of the reasons for this phenomenon is the lack of blood supply due to a non-physiological, regional strain field. The physiological micromechanical forces of skin tissue have been shown to establish localized stress-strain fields. Changes to the physiological strain fields due to skin defects stimulate wound healing by promoting cellular proliferation, migration of epithelial cells, and angiogenesis. It is therefore hypothesized that in order to maintain a healthy skin tissue barrier at the skin-implant interface, the local strain fields of the skin tissue need to be maintained. The primary goal of this proposed research program is to develop and validate the efficacy of a mobile, porous coated dermal barrier to maintain the natural strain field and to confer a stable infection free skin attachment in percutaneous osseointegrated implants. Therefore, the major hypothesis to be tested will be that by allowing the skin to maintain a physiological strain field near the porous coated subdermal barrier, the skin seal will be maintained and skin migration will be prevented. In Aim 1, a percutaneous implant with a dynamic, porous coated subdermal disk will be designed and fabricated that will maintain regional physiological motions of the skin. Using pigs for this model, rates of infection will be compared to a control group (static subdermal disk). In Aims 2(a) and 2(b), the ability of the dynamic, porous coated subdermal disk group to maintain a skin seal and subsequently prevent skin migration will be histologically and biomechanically measured, assessed clinically over 3 and 6 month time periods, and compared to a control group. The projected lifetime health-care cost associated replacement of prostheses for patients who have undergone one limb loss is approximately $500,000. With the establishment of infection-free osseointegrated prosthetic technology, health care costs could be significantly reduced and the lives of 1.7 million amputees could be improved immensely.