Surface Induced Epithelial Differentiation Improves Percutaneous Device Longevity

表面诱导上皮分化可提高经皮装置的使用寿命

• 批准号: 10187780
• 负责人: Sujee Jeyapalina
• 金额: --
• 依托单位: VA SALT LAKE CITY HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10187780
• 关键词: Adhesions; Affinity; Amputees; Animal Model; Animals; Apatites; Autopsy; Biological; Biological Assay; Bone Surface; Bone Tissue; Cells; Cellular Structures; Characteristics; Chemicals; Client satisfaction; Clinical; Cobalt; Country; Data; Defect; Dental Enamel; Dental Implants; Devices; Docking; Environment; Epidermis; Epithelial; European; Excision; Extracellular Matrix; Family suidae; Fibroblasts; Funding; Gingiva; Goals; Grain; Hearing Aids; Hemidesmosomes; High temperature of physical object; Human; Implant; In Vitro; Infection; Life; Limb Prosthesis; Link; Liquid substance; Literature; Longevity; Mediating; Medicine; Modeling; Molecular; Mucous Membrane; Nature; Operative Surgical Procedures; Osseointegration; Osteoblasts; Osteomyelitis; Outcome; Outcome Study; Pathogenicity; Patient-Focused Outcomes; Patients; Pattern; Phase; Phenotype; Polymerase Chain Reaction; Property; Prosthesis; Proteins; Quality of life; RNA; Rattus; Reporting; Research; Research Design; Resected; Sampling; Seal and Protect; Sheep; Sinus; Site; Skin; Stomas; Structure; Surface; Suspensions; System; Techniques; Technology; Testing; Thick; Time; Tissues; Titanium; United States Department of Veterans Affairs; Water fluoridation; Weight-Bearing state; Work; base; biomaterial compatibility; bone; clinical application; cold temperature; commercialization; crystallinity; design; efficacy testing; experimental study; fluorapatite; healing; implantation; improved; in vivo; infection rate; interfacial; keratinocyte differentiation; metallicity; migration; novel; osseointegrated implant; osteoblast differentiation; patient population; preservation; prevent; seal; sheep model; soft tissue; vapor; wound healing

Project Summary: Percutaneous devices are often utilized in medicine and serve as a bridge between the internal and external bodily environments. Dental implants, bone-anchored hearing aids, and percutaneous osseointegrated (OI) devices for amputees are just a few examples. Although widely used, the soft tissue interface (in particularly, the epidermis) with these devices commonly fails to heal properly and disintegrates over time. It is known that immediately following percutaneous implantation; epidermal cells migrate proximally along the implant surface in an attempt to heal the surgically-created soft tissue defect. This phenomenon, termed "epidermal downgrowth," creates a sinus tract around the implant and provides a nidus for bacterial colonization. To improve patient outcomes, our previously funded PRORP study investigated the relationship between crystallinity and coating stability of fluoridated apatites. The data revealed that sintered fluorapatite (FA) possessed the ability to enhance epidermal adhesion and differentiation—a transition highly crucial for preserving the integrity of soft tissue attachment at the implant exit-site—when compared to the current standards of practice, titanium. These data further revealed that osteoblasts and fibroblasts also have affinities to this treated apatite surface, implicating a possible wider application of these apatites for promoting osseointegration as well as skin integration. FA coatings are not currently used in percutaneous osseointegrated (OI) device applications, and thus considered novel. It was believed that commercial technologies that use high temperatures for vaporizing the coating materials might not be suitable for maintaining the optimized crystallinity found within the sintered FA agglomerates. Thus, we used a low- temperature proprietary coating technique, IonTite™, which worked well in initial animal trials in rats and pigs. The overall goal of this proposal is to undertake safe and efficacious testing of this coating in a weight-bearing large animal model prior to assessing its clinical and commercialization potentials. To this end, we hypothesized that epidermally mediated downgrowth, osseointegration and healing outcomes around the percutaneous OI devices would be improved by coating the devices with a bioactive, fluorapatite sintered at 1150°C. Aim 1 will establish an ideal, low temperature, commercial coating technique for applying FA to titanium surfaces. Aim 2 will determine the efficacy of the FA-coated percutaneous OI devices to prevent epidermal downgrowth and to accelerate osseointegration in a weight-bearing large animal model. Aim 3 will confirm the completion of wound healing cascades within the periprosthetic tissue of FA-coated devices by molecular means. The outcome of this proposed study will have immediate clinical applications for the design of both permanent and temporary percutaneous implants. This proposed technology will permit current amputee patient populations, who are suffering from life-long complications associated with the stump-socket interface, to be fitted with the FA-coated percutaneous OI prostheses.

项目摘要： 经皮装置经常用于医学领域，并充当医学与医学之间的桥梁。 牙齿植入物、骨锚式助听器和经皮植入物。 用于截肢者的骨整合（OI）装置只是其中的几个例子，尽管软组织被广泛使用。 这些装置的界面（特别是表皮）通常无法正常愈合并分解 众所周知，经皮植入后，表皮细胞会立即向近端迁移。 沿着种植体表面试图治愈手术造成的软组织缺损这种现象， 称为“表皮向下生长”，在植入物周围形成窦道，并为细菌提供巢穴 为了改善患者的治疗效果，我们之前资助的 PRORP 研究调查了这种关系。 氟化磷灰石的结晶度和涂层稳定性之间的关系数据表明，烧结氟磷灰石。 (FA) 具有增强表皮粘附和分化的能力——这一转变对于 与当前的技术相比，保留了种植体出口处软组织附着的完整性 实践标准，钛这些数据进一步揭示了成骨细胞和成纤维细胞也具有亲和力。 这种经过处理的磷灰石表面，意味着这些磷灰石可能有更广泛的应用，以促进 骨整合和皮肤整合目前尚未用于经皮治疗。 骨整合（OI）设备的应用，因此被认为是新颖的商业化。 使用高温蒸发涂层材料的技术可能不适合 保持烧结 FA 团聚体中的优化结晶度 因此，我们使用了低结晶度。 温度专有涂层技术 IonTite™，在大鼠和猪的初始动物试验中效果良好。 该提案的总体目标是在承重环境中对该涂层进行安全有效的测试 为此，我们在评估其临床和商业化潜力之前建立了大型动物模型。 遭受表皮介导的向下生长、骨整合和周围愈合结果 通过在装置上涂上生物活性氟磷灰石，可以改进经皮 OI 装置 目标 1 将建立一种理想的低温商业涂层技术。 目标 2 将确定 FA 涂层经皮 OI 装置预防 OI 的功效。 Aim 3 将在负重大型动物模型中促进表皮向下生长并加速骨整合。 通过以下方式确认 FA 涂层装置的假体周围组织内伤口愈合级联的完成 这项拟议研究的结果将直接应用于该设计的临床应用。 这项提议的技术将允许目前的永久和临时经皮植入物。 患有与残肢插座相关的终生并发症的截肢患者群体 接口，安装有 FA 涂层的经皮 OI 假体。