Synthetic lubricin biomaterial for osteoarthritis

用于治疗骨关节炎的合成润滑素生物材料

基本信息

批准号：
8904481
负责人：
DAVID A PUTNAM
金额：
$ 21.79万
依托单位：
ARTICULATE BIOMEDICAL, LLC
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-15 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8904481
关键词：
Acute Adhesions Animals Automobile Driving Biocompatible Materials Biomedical Engineering Bone Tissue Canis familiaris Cavia Cell Culture Techniques Clinical Clinical Sciences Clinical Trials Collaborations Complement Activation Counseling Data Degenerative polyarthritis Development Disease Progression Economic Burden Evaluation Exhibits Experimental Designs Fingers Foundations Grant Guidelines Hip region structure Human Hyaluronic Acid Implant In Vitro Industry Intra-Articular Injections Knee Knee Injuries Knee Osteoarthritis Laboratories Lubricants Lubrication Marketing Medical Device Modeling Orthopedic Surgery procedures Outcome Pathway interactions Phase Play Polyethylene Glycols Price Process Protocols documentation Quality of life Rattus Research Research Personnel Rodent Role Route Small Business Technology Transfer Research Spinal Structure Surface Surgeon Temporomandibular Joint Disorders Testing Toxic effect Translations United States Universities Vertebral column Veterinary Medicine Work acrylic acid analog articular cartilage base biomaterial compatibility clinical efficacy college copolymer cost cytotoxicity design economic impact experimental analysis eye dryness genotoxicity human morbidity human mortality implantable device implantation in vivo irritation long bone lubricin meetings palliative pre-clinical prevent product development programs public health relevance research study scale up success

项目摘要

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is a significant contributor to human morbidity and mortality with an economic burden exceeding $30 billion annually in the United States. Lubricin is a natural lubricant of the articular cartilage of the knee, and the intraarticular administration of lubricin prevents OA progression following knee injury. However, the manufacture of lubricin exceeds $10,000/mg, making it an economically impractical product candidate. Recently, a team of biomedical engineers at Cornell University discovered and reduced to practice a synthetic analog of lubricin that prevents OA progression and exhibits excellent biocompatibility in the ACL transection model in rat knees. This lubricin analog, Lubrisynth(r), mimics the structure and function of native lubricin, with the added advantage that cost models indicate commercially viable pricing can be expected with further development. The objective of the proposed research is to advance the translation of Lubrisynth(r) toward clinical use to prevent the progression of osteoarthritis (OA) in the knee. The following Specific Aims are defined to advance the preclinical development of Lubrisynth(r) through the Phase 1 STTR mechanism which is an integrated collaboration between experts at Articulate Biomedical, LLC and Cornell University. Specific Aim 1: Scale-up synthesis of Lubrisynth(r) to the 100 g pilot scale. Lubrisynth(r) is a brush copolymer consisting of a poly acrylic acid backbone with polyethylene glycol sidechains. The synthetic route was designed to allow facile and controlled scale-up in only two steps. The objective of Specific Aim 1 is to apply full factorial experimental design and analysis to establish the scaled process tolerability and the driving factor levels necessary for the reproducible 100 gram-scale synthesis of Lubrisynth(r). The anticipated outcome is a robust quantitated tolerance protocol for the synthesis of Lubrisynth(r) that is amenable to GMP grade manufacture. Specific Aim 2: Establish the in vitro and in vivo biocompatibility profiles of Lubrisynth(r). Lubrisynth(r) will be developed as a Class III medical device. The Industry Guidance for the PMA development pathway of Class III medical devices (i.e., ISO-10993) outlines the specific biocompatibility tests required for implanted devices in contact with tissue/bone for longer than 30 days. In vitro biocompatibility evaluation and in vivo biocompatibility evaluation will be completed as defined by the ISO Guidance. The objective of Specific Aim 2 is to complete both the in vitro and in vivo biocompatibility evaluations of Lubrisynth(r) in accordance with the FDA-accepted guidelines. The anticipated outcome is a thorough and successful analysis of the initial biocompatibility profile of Lubrisynth(r). Collectively, the anticipated outcomes of the proposed work will establish the necessary foundation to begin the commercial development of Lubrisynth(r), and if successful, will clear the way for the STTR Phase 2 Specific Aims (GMP synthesis and clinical efficacy studies).

描述（由适用提供）：骨关节炎（OA）是人类发病率和死亡率的重要贡献者，在美国，经济燃烧每年超过300亿美元。润滑剂是膝关节关节软骨的天然润滑剂，润滑剂的关节内给药可防止膝盖损伤后OA的进展。但是，润滑剂的生产超过10,000美元/毫克，使其成为经济上不切实际的候选产品。最近，康奈尔大学的一支生物医学工程师团队发现并减少了润滑剂的合成类似物，可防止OA进展，并在大鼠膝盖的ACL翻译模型中表现出极好的生物相容性。这种润滑剂类似物，润滑剂（R）模仿天然润滑剂的结构和功能，并具有额外的优势，即成本模型表明，随着进一步的开发，成本模型可以预期在商业上可行的定价。拟议的研究的目的是将lubrisynth（R）转化为临床用途，以防止膝盖中骨关节炎（OA）的进展。定义了以下特定目标，以通过第1阶段的STTR机制推进Lubrisynth（R）的临床前开发，该机制是Articulate Biomedical，LLC和Cornell University专家之间的综合合作。特定目标1：lubrisynth（R）与100 g飞行员的扩大合成规模。 lubriSynth（R）是由带有聚乙烯乙二醇侧链的聚丙烯酸主链组成的刷子共聚物。合成路线的设计旨在仅分两个步骤允许轻松地进行缩放。特定目标1的目的是应用完整的阶乘实验设计和分析以建立缩放过程的耐受性以及可再现100克尺度合成lubrisynth（R）所需的驱动因子水平。预期的结果是适合GMP级制造的Lubrisynth（R）合成的稳健定量的耐受性方案。具体目标2：建立Lubrisynth（R）的体外和体内生物相容性谱。 Lubrisynth（R）将作为III类医学开发设备。 III类医疗设备PMA开发途径的行业指南（即ISO-10993）概述了与组织/骨接触的特定生物相容性测试超过30天。 ISO指导定义的体外生物相容性评估和体内生物相容性评估将完成。特定目的2的目的是根据FDA所接受的指南来完成lubrisynth（R）的体外和体内生物相容性评估。预期的结果是对Lubrisynth（R）的初始生物相容性概况的彻底成功分析。总的来说，拟议工作的预期结果将为开始Lubrisynth（R）的商业发展建立必要的基础，如果成功的话，将为STTR 2阶段的特定目标（GMP综合和临床效率研究）扫清道路。