Osseo-reparative, integrin-specific materials

描述（由申请人提供）：骨组织缺陷，包括植入物-骨结合不良、骨不连骨折以及与骨质疏松症、创伤、关节置换和肿瘤等疾病相关的骨丢失，在残疾和相关医疗保健成本方面具有巨大的社会经济影响。以生物材料为基础的策略，以提高种植体骨整合和骨形成将使生物活性和一体化的骨科和牙科种植技术的发展，以解决这些紧迫的临床问题。本项目的目的是设计具有细胞粘附基序的生物材料，这些基序特异性地结合参与骨形成的整合素受体，以促进植入 骨整合和骨修复。我们的中心假设是，促成骨，整合素特异性配体的精确介绍将直接成骨细胞分化，种植体骨整合和骨修复。基于我们对两种工程化整合素特异性配体的研究，我们提出了这一假设，这两种配体概括了其天然配体的二级结构（来自胶原蛋白I的三螺旋GFOGER肽用于a2 b1整合素，来自纤连蛋白的重组FNIII 7 -10用于a5 b1整合素），并促进成骨细胞分化、植入物骨整合和骨缺损修复。目的1：设计整合素特异性涂层，增强健康和卵巢切除大鼠的螺钉-骨整合。目标二：工程聚（乙二醇）为基础的水凝胶提出整合素特异性配体作为移植模板和BMP-2的交付车辆的非愈合骨缺损的修复。这项研究是创新的，因为它专注于工程新的生物材料涂层和水凝胶与特异性的促成骨整合素，以促进骨形成和修复。这项工作将建立在何种程度上介绍整合素特异性配体增强螺钉骨整合在健康和骨质疏松骨。此外，我们还将设计新型水凝胶作为移植材料和BMP-2载体，用于增强非愈合性骨缺损的修复。总的来说，这些研究将建立新型生物活性材料，增强骨形成和植入物整合，以改善各种临床应用中的骨修复。

DESCRIPTION (provided by applicant): Bone tissue deficiencies, including poor implant-bone integration, non-union fractures, and bone loss associated with diseases such as osteoporosis, trauma, joint replacements, and tumors, have tremendous socioeconomic impact in terms of disability and related health care costs. Biomaterial-based strategies to enhance implant osseointegration and bone formation will enable the development of biologically active and integrative orthopaedic and dental implant technologies to address these pressing clinical issues. The objective of this project is to engineer biomaterials presenting cell adhesive motifs that specifically bind to integrin receptors involved in bone formation in order to promote implant osseointegration and bone repair. Our central hypothesis is that precise presentation of pro-osteogenic, integrin-specific ligands will direct osteoblastic differentiation, implant osseointegration and bone repair. We have formulated this hypothesis based on our work with two engineered integrin-specific ligands that recapitulate the secondary structure of their native ligands (triple-helical GFOGER peptide from collagen-I for a2b1 integrin, recombinant FNIII7-10 from fibronectin for a5b1 integrin) and promote osteoblastic differentiation, implant osseointegration, and repair of bone defects. Aim 1: Engineer integrin-specific coatings that enhance screw-bone integration in healthy and ovariectomized rats. Aim 2: Engineer poly(ethylene glycol)-based hydrogels presenting integrin-specific ligands as grafting templates and BMP-2 delivery vehicles for the repair of non-healing bone defects. This research is innovative because it focuses on engineering novel biomaterial coatings and hydrogels with specificity for pro-osteogenic integrins to promote bone formation and repair. This work will establish the extent to which presentation of integrin-specific ligands enhances screw-bone integration in both healthy and osteoporotic bone. Also, we will engineer novel hydrogels as grafting materials and BMP-2 delivery vehicles for enhanced repair of non-healing bone defects. Collectively, these studies will establish novel bioactive materials that enhance bone formation and implant integration for improved bone repair in various clinical applications.