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: 10391337
• 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 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10391337
• 关键词: Adhesions; Affinity; Amputees; Animal Model; Animals; Apatites; Autopsy; 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：经皮穿刺器在医学上经常被使用，并作为 身体的内部和外部环境。牙科植入物、骨锚式助听器和经皮 截肢者的骨整合(OI)装置只是几个例子。虽然被广泛使用，但软组织 与这些装置的接口(尤其是表皮)通常不能正确愈合和解体 随着时间的推移。已知，在经皮植入后，表皮细胞立即向近端迁移 以试图修复手术造成的软组织缺陷。这种现象， 被称为“表皮绒毛生长”，在植入物周围形成一个窦道，为细菌提供了一个病灶。 殖民主义。为了改善患者的预后，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与涂层稳定性之间的关系。数据显示，烧结的氟磷灰石 (FA)具有增强表皮黏附和分化的能力-这一转变对 保持种植体出口部位软组织附着的完整性--与目前的 实践标准，钛。这些数据进一步表明，成骨细胞和成纤维细胞也具有亲和力 这种处理后的磷灰石表面，暗示了这些磷灰石可能更广泛的应用，以促进 骨整合和皮肤整合。FA涂层目前不用于经皮 骨集成(OI)设备的应用，因此被认为是新奇的。人们认为，商业广告 使用高温蒸发涂层材料的技术可能不适合 保持在烧结的FA团聚体中发现的最佳结晶度。因此，我们使用了低- 温度专利涂层技术IonTite™，在大鼠和猪的初步动物试验中效果良好。 这项建议的总体目标是在承重的情况下对这种涂层进行安全有效的测试 在评估其临床和商业化潜力之前，先建立大动物模型。为此，我们 假设表皮介导的生长抑制、骨整合和周围的愈合结果 通过将生物活性的氟磷灰石涂覆在设备上，经皮OI设备将得到改进 在1150°C下烧结Aim 1将建立一种理想的、低温的、商业化的涂层技术 FA到钛表面。目的2将确定FA涂层经皮OI装置的有效性，以防止 在负重的大型动物模型中，表皮向下生长并加速骨整合。目标3将 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 分子手段。这项拟议研究的结果将立即对设计产生临床应用。 永久性和临时性的经皮植入。这项拟议的技术将允许当前 截肢患者群体，他们遭受着与残腔相关的终生并发症的痛苦 界面，与FA涂层的经皮OI假体相匹配。