Peptide conjugation for Co-Delivery of Growth Factors and Stem Cells

用于共同递送生长因子和干细胞的肽缀合

• 批准号: 8250588
• 负责人: Shrikumar Ambujakshan Nair
• 金额: $ 74.77万
• 依托单位: AFFINERGY, LLC
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8250588
• 关键词: Address; Adipose tissue; Affinity; Allogenic; Animal Model; Aspirate substance; Attention; Autologous; Bacteriophages; Binding; Biocompatible; Biocompatible Materials; Biological; Bone Marrow; Bone Morphogenetic Proteins; Bone Transplantation; Cell Count; Cells; Chemistry; Clinic; Clinical; Clinical Trials; Collagen; Defect; Dose; Filler; Frequencies; Goals; Growth Factor; Healed; Implant; In Vitro; Libraries; Life; Link; Liquid substance; Marketing; Mature Bone; Mesenchymal Stem Cells; Modeling; Oryctolagus cuniculus; Osteogenesis; Outcome; Peptides; Phage Display; Phase; Phenotype; Process; Production; Proteins; Radial; Running; Safety; Signaling Molecule; Site; Specificity; Stem cells; Sterilization; Technology; Testing; Therapeutic; Therapeutic Effect; Tissues; Treatment Efficacy; biomaterial compatibility; bone; bone healing; bone morphogenetic protein 2; bone morphogenetic protein 6; bone morphogenetic protein 7; cell growth; cell type; comparative efficacy; cost; cost effective; healing; improved; manufacturing process; manufacturing scale-up; medical implant; osteogenic; programs; protein aminoacid sequence; prototype; research study; scaffold; scale up

DESCRIPTION (provided by applicant): Autologous stem cells and growth factors provide valuable therapies for a variety of indications. When stem cells and growth factors are co-delivered, they produce a greater therapeutic effect than delivery of either stem cells or growth factors alone. However, the use of growth factors in the clinic is limited by the challenges of retaining the proteins at the site of healing. The use of stem cells is challenging because of the low frequency of cells in autologous tissue. To address these difficulties, Affinergy used its core technology, phage display biopanning, to screen phage libraries containing billions of candidate peptide sequences. From this process, we identified peptides that bind with high affinity and specificity to growth factors and stem cells. In our Phase II project, we developed a biomaterial coated with a growth factor-binding peptide that captures and retains growth factors significantly longer than the commercially available biomaterials. We demonstrated in animal models that this biomaterial has greater therapeutic efficacy than commercially available products when combined with autologous tissue containing the target growth factor. In this Competing Renewal application, we propose to further enhance the efficacy of this product through the addition of a stem cell-binding peptide, also identified by phage display. The combination of the two peptides will increase the capture of stem cells from autologous tissue onto the material and provide a synergistic effect with the capture and retention of growth factors. PUBLIC HEALTH RELEVANCE: Stem cells and growth factors provide valuable therapies for a variety of indications, and co-delivery of stem cells with growth factors produces a greater therapeutic effect than delivery of either stem cells or growth factors alone. In this application, we propose to develop a biomaterial that can bind and retain both growth factors and stem cells.

描述（由申请人提供）：自体干细胞和生长因子为各种适应症提供了有价值的治疗方法。当干细胞和生长因子共同递送时，它们产生比单独递送干细胞或生长因子更大的治疗效果。然而，生长因子在临床中的使用受到将蛋白质保留在愈合部位的挑战的限制。干细胞的使用是具有挑战性的，因为自体组织中的细胞频率低。为了解决这些困难，Affinergy使用其核心技术，噬菌体展示生物淘选，筛选含有数十亿个候选肽序列的噬菌体文库。从这个过程中，我们确定了肽，结合与生长因子和干细胞的高亲和力和特异性。在我们的第二阶段项目中，我们开发了一种生物材料，该材料涂覆有生长因子结合肽，其捕获和保留生长因子的时间比市售生物材料长得多。我们在动物模型中证明，当与含有靶向生长因子的自体组织结合时，这种生物材料具有比市售产品更高的治疗功效。在此竞争更新应用中，我们建议通过添加干细胞结合肽（也通过噬菌体展示鉴定）来进一步增强该产品的功效。两种肽的组合将增加干细胞从自体组织捕获到材料上，并提供与生长因子的捕获和保留的协同效应。 公共卫生关系：干细胞和生长因子为多种适应症提供了有价值的疗法，并且干细胞与生长因子的共同递送比单独递送干细胞或生长因子产生更大的治疗效果。在这个应用中，我们提出开发一种生物材料，可以结合和保留生长因子和干细胞。