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：经皮装置在医学上经常被使用，并作为一个桥梁