Improved orthopaedic repairs through mechanically optimized, adhesive biomaterials

通过机械优化的粘合生物材料改善骨科修复

• 批准号: 9241245
• 负责人: Stephen W Linderman
• 金额: $ 4.86万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9241245
• 关键词: Activities of Daily Living; Adhesions; Adhesives; Age; Animal Model; Behavior; Binding; Biocompatible Materials; Biomechanics; Canis familiaris; Cells; Chemistry; Clinical; Clinical Trials; Coculture Techniques; Cyanoacrylates; Elastin; Ensure; Environment; Failure; Fibroblasts; Flexor; Foundations; Gene Expression; Goals; Hand; Histologic; Implant; In Vitro; Individual; Inflammation; Inflammatory; Injury; Integrins; Laceration; Lead; Length; Ligaments; Measures; Mechanics; Modeling; Modernization; Musculoskeletal; Nylons; Operative Surgical Procedures; Orthopedic Surgery procedures; Orthopedics; Outcome; Peptides; Property; Proteins; Protocols documentation; Reaction; Rehabilitation therapy; Repeat Surgery; Research; Resistance; Risk; Rotator Cuff; Rupture; Scheme; Shear Strength; Silk; Site; Stress; Surface; Surgeon; Surgical sutures; Techniques; Technology; Tendon structure; Testing; Time; Tissues; Training; base; biomaterial compatibility; chemical property; clinical practice; clinically relevant; crosslink; design; disability; elastomeric; healing; implantation; improved; improved outcome; in vivo; mathematical model; mechanical properties; new technology; novel; overexpression; pre-clinical; preclinical study; public health relevance; reconstruction; repaired; resilience; response; subcutaneous; surface coating; tissue reconstruction; tissue repair; tool

DESCRIPTION (provided by applicant): Suture materials and surgical knot tying techniques have improved dramatically since their first use over five millennia ago. However, the approach remains limited by the ability of the suture to transfer load to tissue at suture anchor points. Ths is especially problematic for repairs that require high strength such as tendon and ligament repairs, where repair-site elongation and rupture rates are as high as 94% for rotator cuff and 48% for flexor tendon. The goal of this proposal is to revolutionize suture repair technology by creating adhesive-coated sutures that distribute load transfer over the suture's length, leading to substantial improvements in surgical repair strength. Using mathematical models that define desirable adhesive material properties for improving tendon repair strength, the first aim of the study seeks to develop adhesive biomaterials with optimized mechanical properties to improve load distribution of tendon repairs. These novel bioadhesive materials will be created using a suite of tools to control both mechanical and chemical properties. Adhesive biomaterials will be applied to sutures and evaluated biomechanically in ex vivo flexor digitorum profundus tendons. The second aim will evaluate biocompatibility of adhesive biomaterials that provide at least a 30% improvement in ex vivo repair strength. Biocompatibility will be assessed via cell- and tissue-level responses to the bioadhesives after co- culturing primary tendon fibroblasts with the adhesive biomaterials in vitro, as well as implanting the adhesive biomaterials subcutaneously in an in vivo animal model. After establishing the ex vivo mechanical efficacy and in vivo biocompatibility, the third aim will determine efficacy of adhesive sutures for improved outcomes after in vivo tendon repairs in a preclinical surgical study. Fully trained orthopedic surgeons wil apply this new technology in a clinically relevant, established large animal model for flexor tendon repair to assess surgical outcomes. This research will develop a novel suturing platform that fundamentally changes the mechanical principles of suture repairs, transforming this age-old technology to dramatically improve surgical repair strength. The proposed research will demonstrate the clinical utility of adhesive-coated sutures through preclinical studies that lay th foundation for clinical trials. This research has the potential to improve repair strength, enable more aggressive rehabilitation protocols, and decrease surgical repair failures for tendon and ligament reconstruction.

描述(由申请人提供)：缝合材料和外科打结技术自五千多年前首次使用以来已经有了显著的改进。然而，该方法仍然受到缝合线将负荷转移到缝合线锚点处组织的能力的限制。这对于肌腱和韧带修复等需要高强度的修复尤其成问题，修复部位的伸长率和断裂率在肩袖高达94%，屈肌腱高达48%。这项提案的目标是通过创造粘合剂涂层缝合线来革命性地修复缝合线技术，这种缝合线在缝合线的长度上分配载荷传递，导致 手术修复强度有了实质性的提高。为了提高肌腱修复强度，本研究的第一个目标是利用定义理想的粘合材料性能的数学模型，开发具有优化机械性能的粘合生物材料，以改善肌腱修复的载荷分布。这些新型的生物粘合材料将使用一套工具来控制机械和化学性能。将粘附性生物材料应用于指深屈肌腱的缝合，并对其进行生物力学评价。第二个目标是评估粘附性生物材料的生物相容性，这些材料在体外修复强度方面至少提高了30%。在体外将原代肌腱成纤维细胞与粘附性生物材料共培养，并将粘附性生物材料植入体内动物模型皮下，通过细胞和组织水平对生物粘附剂的反应来评估生物相容性。在确定了体外机械效果和体内生物相容性后，第三个目标将在临床前外科研究中确定粘合缝合的有效性，以改善体内肌腱修复后的结果。训练有素的骨科医生将把这项新技术应用于临床相关的、已建立的屈肌腱修复的大型动物模型中，以评估手术结果。这项研究将开发一种新的缝合平台，从根本上改变缝合修复的机械原理，改造这项古老的技术，显著提高手术修复强度。这项拟议的研究将通过为临床试验奠定基础的临床前研究来证明粘合剂涂层缝线的临床实用性。这项研究有可能提高修复强度，实现更积极的康复方案，并减少肌腱和韧带重建的手术修复失败。