Bioactive Peptide Coatings for Synthetic Bone Grafts in Dental Applications

用于牙科应用中合成骨移植的生物活性肽涂层

• 批准号: 7217628
• 负责人: Hanne Gron
• 金额: $ 26.45万
• 依托单位: AFFINERGY ,INC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-15 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7217628
• 关键词: Adult; Adverse effects; Affinity; Allergic Reaction; Allografting; Autologous Transplantation; Binding; Biopolymers; Blood Platelets; Bone Diseases; Bone Substitutes; Bone Surface; Bone Transplantation; Carrying Capacities; Cell Count; Cell Therapy; Cells; Chemistry; Clinical; Defect; Dental; Dental Implants; Disease; Dose; Elements; Face; Floor; Goals; Gold; Growth Factor; Harvest; Healed; Health; Human; Institutes; Lead; Libraries; Mandible; Mediating; Mesenchymal Stem Cells; Metals; Modeling; Morbidity - disease rate; Organ Transplantation; Osteoblasts; Osteogenesis; Outcome; Patients; Peptides; Periodontitis; Phage Display; Phenotype; Physiological; Placement; Plasma; Plastics; Procedures; Production; Property; Quality of life; Range; Rattus; Recombinant Proteins; Recombinants; Research; Risk; Rivers; Safety; Screening procedure; Sinus; Source; Specific qualifier value; Specificity; Standards of Weights and Measures; Stem cells; Surface; Surgeon; Techniques; Technology; Testing; To specify; Tooth structure; Transplanted tissue; Work; Xenograft procedure; base; bone; bone healing; bone loss; bone morphogenic protein; chemical synthesis; cost; craniofacial; disease transmission; experience; healing; immunogenicity; improved; in vivo; interest; neutralizing antibody; osteoinductive factor; protein aminoacid sequence; tricalcium phosphate

DESCRIPTION (provided by applicant): According to the National Institute of Dental and Craniofacial Research, 86% of adults over 70 years have at least moderate periodontitis and over a quarter have lost their teeth, which has serious repercussion on health and quality of life. Because of bone loss caused by this disease, bone grafting is routinely necessary prior to the placement of dental implants. Autograft bone is considered the gold standard because of its osteogenic cells, osteoinductive factors, and osteoconductive properties. However, because of procurement morbidity and constraints on the quantity of autograft, surgeons also use allografts, xenografts, and synthetic materials. Allograft and xenograft are favored because they possess some osteoinductive elements especially in demineralized forms. However, these natural materials also have limitations including immunogenicity, risk of disease transmission, limited availability, and high procurement costs. Many synthetic alternatives have been developed, but they are generally not as effective as the natural materials due to the absence of osteoinductive and osteogenic properties. In this project, we are attempting to improve synthetic bone substitutes with Affinergy's linker peptides. If synthetics were made more osteoinductive, they could provide an unlimited source of graft material that would eliminate many of the drawbacks of autograft, allograft, and xenograft. Affinergy's peptide linkers provide two improvements on existing bone grafts that could significantly improve clinical outcomes by stimulating bone healing. First, we expect that coating bone graft materials with binding peptides will significantly improve their ability to retain exogenously delivered osteogenic factors such as recombinant proteins and progenitor cells. Secondly, we believe these peptide coatings have the potential to promote the attachment of endogenous growth factors and cells onto the surface of bone grafts. The goal of this proposal is to demonstrate that bi-functional peptide coatings can improve the ability of a synthetic bone graft to promote bone healing by increasing the attachment and retention of osteogenic growth factors and cells. First, using phage display techniques, we will identify tricalcium phosphate (TCP) binding peptides. Next, we will synthesize combinations of Affinergy's existing BMP-2 and osteoblast binding sequences and the newly identified TCP binding peptides. These candidate bi-functional linker peptides will be tested for their ability to bind BMP-2 and osteoblasts on TCP matix, while retaining BMP-2's activity and the osteolbasts' phenotype. Finally, a rat mandible defect model will be used to investigate the ability of peptide coatings to increase bone formation at lower doses of recombinant BMP-2. Growth factor and osteoblast binding peptides will also be tested alone and in combination to assess their ability to increase bone formation compared to untreated TCP by promoting the attachment of endogenous growth factors and osteoprogenitor cells. Bone grafting is routinely necessary prior to the placement of dental implants. Natural materials like autograft, bone harvest from the patient, and allograft, cadaveric bone, have traditionally been used in these grafting procedures. They have many limitations including complications associated with autograft harvest; and immunogenicity, risk of disease transmission, limited availability, and high procurement costs associated with allograft. Many synthetic alternatives have been developed, but they are generally not as effective as the natural materials. In this project, we are attempting to improve synthetic bone substitutes with Affinergy's linker peptides. We expect that peptide coatings will improve the ability of synthetic materials to stimulate bone healing by promoting the attachment of bone promoting growth factors and cells on the surface of these synthetic alternatives.

描述（由申请人提供）：根据美国国家牙科和颅面研究所的说法，有86％的成年人至少患有中度牙周炎，四分之一以上的牙齿却失去了牙齿，这对健康和生活质量产生了严重的影响。由于这种疾病引起的骨质流失，在放置牙齿植入物之前，通常需要进行骨移植。自体移植骨被认为是黄金标准，因为其成骨细胞，骨诱导因子和骨导导特性。但是，由于采购发病率和自体量的限制，外科医生还使用同种异体移植，异种移植物和合成材料。同种异体移植和异种移植受到青睐，因为它们具有某些骨诱导元素，尤其是在非矿化形式中。但是，这些天然材料也有局限性，包括免疫原性，疾病传播的风险，有限的可用性和高采购成本。已经开发了许多合成替代方法，但由于缺乏骨诱导和成骨特性，它们通常不如天然材料有效。在这个项目中，我们试图用Affinergy的接头肽来改善合成骨替代物。如果使合成剂变得更具骨诱导性，则可以提供无限的移植物材料来源，以消除自体移植，同种异体移植和异种移植的许多缺点。 Affinergy的肽接头对现有的骨移植物进行了两种改进，可以通过刺激骨骼愈合来显着改善临床结果。首先，我们预计具有结合肽的涂层骨移植物将显着提高其保留外源输送的成骨因子（例如重组蛋白和祖细胞）的能力。其次，我们认为这些肽涂层具有促进内源性生长因子和细胞附着在骨移植表面上的潜力。该提案的目的是证明双功能肽涂层可以通过增加成骨生长因子和细胞的附着和保留来提高合成骨移植物来促进骨骼愈合的能力。首先，使用噬菌体显示技术，我们将识别磷酸三钙（TCP）结合肽。接下来，我们将合成Affinergy现有的BMP-2和成骨细胞结合序列以及新鉴定的TCP结合肽的组合。这些候选双功能连接器肽将测试其在TCP Matix上结合BMP-2和成骨细胞的能力，同时保留BMP-2的活性和骨栓塞的表型。最后，将使用大鼠下颌骨缺陷模型来研究肽涂层在较低剂量的重组BMP-2下增加骨形成的能力。生长因子和成骨细胞结合肽也将单独测试，并结合使用，以评估其与未经处理的TCP相比，通过促进内源性生长因子和骨质体细胞的附着来增加骨形成的能力。在放置牙齿植入物之前，通常需要骨移植。传统上，自然材料（例如自体移植，患者的骨骼收获）以及同种异体移植物尸体骨骼已被用于这些嫁接程序。它们有许多局限性，包括与自体移植相关的并发症；以及免疫原性，疾病传播的风险，有限的可用性以及与同种异体移植相关的高采购成本。已经开发了许多合成替代品，但通常不像天然材料那样有效。在这个项目中，我们试图用Affinergy的接头肽来改善合成骨替代物。我们预计肽涂层将通过促进骨骼促进生长因子和细胞在这些合成替代方面的附着来提高合成材料刺激骨骼愈合的能力。