Multidomain Peptides for Inflammation and Angiogenic Mediated Tissue Regeneration

用于炎症和血管生成介导的组织再生的多域肽

• 批准号: 8893044
• 负责人: Vivek Kumar
• 金额: $ 4.87万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-05-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8893044
• 关键词: Adhesives; Amino Acid Sequence; Amino Acids; Animal Model; Area; Aspirate substance; Behavior; Binding; Biochemistry; Biological; Biomimetics; Blood Vessels; Canned Foods; Catheters; Cell Proliferation; Cell-Cell Adhesion; Cells; Cellular Infiltration; Chronic; Clinical; Coupled; Data; Dental; Dental Pulp; Dental caries; Dental crowns; Dentin; Dentistry; Development; Drug Controls; Engineering; Environment; Evaluation; Evolution; Excision; Extracellular Matrix; Family; Filler; Gel; Generations; Growth; Growth Factor; Healed; Health; Height; High Prevalence; Human; Hydrogels; Immune; Immune response; Immunocompromised Host; Implant; In Vitro; Infection; Inflammation; Inflammatory; Inflammatory Response; Injectable; Interleukin-4; Lead; Length; Lesion; Life; Measures; Mechanics; Mediating; Methods; Modeling; Monocyte Chemoattractant Protein-1; Natural regeneration; Needles; Nerve Regeneration; Operative Surgical Procedures; Outcome; Pain; Pathogenesis; Pathologic; Pathology; Peptides; Pharmaceutical Preparations; Phenotype; Procedures; Protein Engineering; Pulp Canals; Reaction; Recovery; Residual state; Resolution; Resources; Rice; Second Look Surgery; Series; Site; Stem cells; Syringes; System; Techniques; Tertiary Protein Structure; Time; Tissue Engineering; Tissues; Tooth Loss; Tooth structure; Trauma; Universities; Vascular Endothelial Growth Factors; Vertebral column; Width; Work; Wound Healing; age related; base; biomaterial compatibility; blood vessel development; cellular engineering; collaborative environment; college; controlled release; cost; cytokine; cytotoxicity; design; experience; healing; human stem cells; human tissue; improved; in vitro testing; in vivo; inflammatory modulation; migration; mimetics; mouse model; nanofiber; nanometer; pathogen; permanent tooth; protein aminoacid sequence; response; scaffold; standard of care; success; tissue regeneration; translational medicine; vascular tissue engineering

DESCRIPTION (provided by applicant): Recently developed Multidomain Peptides (MDP) can be triggered to self-assemble into nanofiber hydrogels. Given the simplicity and versatility offered by these short chain amino acid sequences, the physical and biological responses can be tuned. Incorporation of cell degradation sites into the amino acid backbone allow for peptide hydrogels to be broken down by infiltrating cells. Similarly, engineering cell binding domains into the peptide sequence, offer a method to allow cell adhesion and proliferation. Together, mixtures of degradable and non-degradable peptides will allow time-dependent enzymatic breakdown with cellular infiltration. Hydrogels can be easily aspirated into a syringe and delivered via needle, with mechanical recovery. This will allow cytokines and growth factors to effectively be delivered into biological scaffolds or pathologic lesions - such as hollowed out teeth during a root canal. Any procedure or implant (including a root canal) will induce an inflammatory reaction. While others have tried to obviate this inflammatory response, we aim to modulate the infiltrating immune cells' response to one of healing as opposed to chronic inflammation/implant rejection. This has been demonstrated with specific cytokines that guide inflammatory cells to a healing and resolution phenotype. While not attempted with dental regeneration, prior studies have shown efficacy in models including nerve regeneration and vascular tissue engineering. Further, addition of a molecule that aids in blood vessel formation will help in creating living tissue. These additives will be tested in vitro with immune cells, cels from blood vessels and dental stem cells. The work will culminate with in vivo application of these cytokine/ growth factor loaded gels - where inflammatory cells will be guided to resolve inflammation, infiltrating cells will develop blood vessels and replace the nanofiber scaffolding with native living tissue. This project is organized into 3 aims. Aim 1 will determine the degradation of MDP, and loading and release of cytokines / growth factors. Aim 2 will elucidate the cellular behavior of immune cells, blood vessel cells and dental pulp stem cells in loaded MDP nanofibers. Aim 3 will determine biocompatibility and immune response of loaded MDP nanofibers in an animal model of wound healing and dental pulp regeneration. While showcasing applicability for dental regeneration, loaded peptide scaffolds can be tailored to a variety of other applications for tissue engineering and translational medicine.

描述（由申请人提供）：最近开发的多结构域肽（MDP）可被触发自组装成可降解水凝胶。鉴于这些短链氨基酸序列提供的简单性和多功能性，可以调节物理和生物反应。将细胞降解位点并入氨基酸骨架中允许肽水凝胶被浸润细胞分解。类似地，将细胞结合结构域工程化为 肽序列提供了一种允许细胞粘附和增殖的方法。总之，可降解和不可降解肽的混合物将允许时间依赖性酶促分解和细胞浸润。水凝胶可以很容易地吸入注射器，并通过针头输送，机械回收。这将允许细胞因子和生长因子有效地被递送到生物支架或病理损伤中-例如在根管治疗期间挖空的牙齿。任何手术或种植体（包括根管）都会引起炎症反应。虽然其他人试图抑制这种炎症反应，但我们的目标是调节浸润免疫细胞对愈合的反应，而不是慢性炎症/植入物排斥反应。这已经用引导炎性细胞愈合和消退表型的特异性细胞因子证明。虽然没有尝试与牙齿再生，以前的研究已经表明，包括神经再生和血管组织工程模型的疗效。此外，添加有助于血管形成的分子将有助于创造活组织。这些添加剂将在体外用免疫细胞、血管干细胞和牙齿干细胞进行测试。这项工作将最终在体内应用这些细胞因子/生长因子加载凝胶-其中炎症细胞将被引导以解决炎症，浸润细胞将发育血管并用天然活组织取代血管支架。该项目分为三个目标。目的1将确定MDP的降解以及细胞因子/生长因子的负载和释放。目的2研究免疫细胞、血管细胞和牙髓干细胞在负载MDP纳米纤维中的细胞行为。目的3将确定负载MDP纳米纤维在伤口愈合和牙髓再生的动物模型中的生物相容性和免疫应答。在展示牙齿再生的适用性的同时，负载的肽支架可以针对组织工程和转化医学的各种其他应用进行定制。