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: 10614520
• 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/10614520
• 关键词: Acceleration; Adhesions; Affinity; Amputees; Animal Model; Animals; Apatites; Autopsy; Biocompatible Coated Materials; Biological Assay; Bone Surface; Bone Tissue; Cells; Characteristics; Chemicals; Client satisfaction; Clinical; Cobalt; Country; Data; Defect; Dental Enamel; Dental Implants; Devices; Docking; Environment; Epidermis; Epithelium; European; Excision; Extracellular Matrix; Extracellular Structure; Family suidae; Fibroblasts; Funding; Gingiva; Goals; Grain; Hearing Aids; Hemidesmosomes; High temperature of physical object; Human; Implant; In Vitro; Infection; Invaded; 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; Porosity; Property; Prosthesis; Proteins; Quality of life; RNA; Rattus; Reporting; Research; Research Design; Resected; Sampling; Seal and Protect; Second Look Surgery; 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; biomaterial compatibility; bone; cell motility; clinical application; cold temperature; commercialization; crystallinity; design; efficacy evaluation; efficacy testing; experimental study; fluorapatite; healing; implantation; improved; in vivo; infection rate; interfacial; keratinocyte differentiation; metallicity; novel; osseointegrated implant; osteoblast differentiation; patient population; preservation; prevent; seal; sheep model; soft tissue; surface coating; 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.

项目概述：经皮器械经常用于医学，并作为与 内部和外部身体环境。牙科植入物、骨锚式助听器和经皮 用于截肢者的骨整合（OI）装置只是几个例子。虽然被广泛使用，但软组织 与这些装置的界面（特别是表皮）通常不能适当地愈合并分解 随着时间众所周知，经皮植入后，表皮细胞立即向近端迁移， 沿着植入物表面，以试图治愈外科手术产生的软组织缺损。这种现象， 称为“表皮向下生长”，在植入物周围形成窦道， 殖民化为了改善患者的预后，我们先前资助的PRORP研究调查了 结晶度和涂层稳定性之间的关系。数据显示烧结的氟磷灰石 (FA)具有增强表皮粘附和分化的能力，这是一个对 与当前相比， 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， 这意味着这些磷灰石可能更广泛地应用于促进 骨整合以及皮肤整合。FA涂层目前未用于经皮 骨整合（OI）装置应用，因此被认为是新颖的。据信，商业 使用高温蒸发涂层材料的技术可能不适合于 保持在烧结的FA附聚物内发现的最佳结晶度。我曾用过一种低调的方式。 IonTite™是一种高温专有涂层技术，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设备中对该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，需要对大型动物模型进行评估。为此我们 假设表皮介导的向下生长、骨整合和周围的愈合结果 通过用生物活性的氟磷灰石涂覆经皮OI装置， 在1150°C下烧结。目标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器械预防 表皮向下生长和加速骨整合。目标3将 通过以下方式确认FA涂层器械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临床应用的设计 永久性和临时性经皮植入物。这项技术将使目前 截肢患者人群，他们患有与残肢插座相关的终身并发症 接口，以配合FA涂层经皮OI假体。