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

描述(申请人提供)：改进的假体接口，以改善康复将外固定假体直接连接到骨固定的、骨整合的植入物上，这种植入物通过皮肤穿透皮肤，被认为是肢体丧失患者常用插座型技术的替代方案。负荷型经皮骨结合种植体的主要失效模式之一是在皮肤-种植体界面发生感染。因此，骨集成假体作为一种潜在的临床治疗的成功在很大程度上依赖于建立一种皮肤密封性，以维持在该界面上对感染的天然屏障。在这项技术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，一种真皮下多孔的涂层屏障最初可以附着在皮肤上，防止感染长达九个月。这一数据还表明，皮肤移位在经皮柱周围以每月1.6？0.5毫米的速度变得常见。此外，皮肤-种植体界面的组织学检查显示，与经皮柱相邻的上皮脊变平和失活，下面没有血管化的乳头状真皮。愈合伤口周围的上皮变平是正常的，但即使在我们的研究中看到的术后6个月后，仍然存在网脊变平的持续存在，这在临床上仍然是令人担忧的。这些观察表明伤口愈合受损，这可能是观察到的皮肤沿着真皮下屏障迁移的原因。据认为，造成这种现象的原因之一是由于非生理性、区域性应变场导致的血液供应不足。皮肤组织的生理微机械作用力已被证明建立局部应力-应变场。由于皮肤缺陷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，假设为了在皮肤-植入物界面上保持健康的皮肤组织屏障，需要保持皮肤组织的局部应变场。这项拟议研究计划的主要目标是开发和验证一种可移动的、多孔涂层真皮屏障的有效性，以维持自然应变场，并在经皮骨集成植入物中提供稳定的无感染皮肤附着。因此，需要检验的主要假设是，通过允许皮肤在多孔涂层真皮下屏障附近保持生理应变场，将保持皮肤密封并防止皮肤迁移。在目标1中，将设计和制造一种具有动态、多孔涂层皮下圆盘的经皮植入物，以保持皮肤的局部生理运动。在这个模型中，猪的感染率将与对照组(静态皮下视盘)进行比较。在AIMS 2(A)和2(B)中，将对动态、多孔涂层真皮下圆盘组维持皮肤密封并随后防止皮肤迁移的能力进行组织学和生物力学测量，并在3个月和6个月的时间段内进行临床评估，并与对照组进行比较。为失去一条肢体的患者更换假肢相关的预计终生保健费用约为50万美元。随着无感染骨集成假体技术的建立，医疗成本将显著降低，170万截肢者的生活将得到极大改善。

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.