Multidomain Peptides for Inflammation and Angiogenic Mediated Tissue Regeneration

项目摘要 最近开发的多结构域肽（MDP）可以被触发以自组装成水凝胶。 考虑到这些短链氨基酸序列提供的简单性和多功能性， 生物反应是可以调节的。将细胞降解位点并入氨基酸骨架中允许 用于肽水凝胶被渗透细胞分解。类似地，将细胞结合结构域工程化到 肽序列，提供了一种允许细胞粘附和增殖的方法。总之，可降解的 而不可降解的肽将允许时间依赖性的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。 任何手术或植入物（包括根管）都会引起炎症反应。虽然其他人尝试过 为了抑制这种炎症反应，我们的目标是调节浸润性免疫细胞对以下之一的反应： 愈合，而不是慢性炎症/植入物排斥。这一点已经得到了具体的证明。 引导炎性细胞愈合和消退表型的细胞因子。虽然没有尝试与牙科 再生，先前的研究已经在包括神经再生和血管组织的模型中显示出功效 工程.此外，添加一种有助于血管形成的分子将有助于创造生命。 组织.这些添加剂将在体外用免疫细胞、血管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/生长因子加载的凝胶-其中 炎症细胞将被引导以解决炎症，浸润细胞将发展血管， 用天然的活组织替换骨支架。该项目分为三个目标。目标1将 测定MDP的降解以及细胞因子/生长因子的加载和释放。目标2将阐明 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将确定负载的MDP纳米纤维在动物模型中的生物相容性和免疫应答。 伤口愈合和牙髓再生。在展示牙齿再生的适用性的同时， 肽支架可以被定制为用于组织工程和翻译的多种其它应用 药

Project Summary 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, cells 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.