Modular Self-Assembled Coatings for Biomaterials

用于生物材料的模块化自组装涂层

• 批准号: 8256536
• 负责人: Joel H Collier
• 金额: $ 32.94万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2013-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8256536
• 关键词: 3-Dimensional; Affect; Animal Model; Appointment; Architecture; Attention; Basement membrane; Binding; Biocompatible Materials; Biological; Blood; Blood Vessel Prosthesis; Cell Culture Techniques; Cells; Collagen; Complex; Cornea; Cues; Data; Dermal; Development; Devices; Drug Formulations; Elements; Endothelial Cells; Endothelium; Engineering; Epithelial Cells; Epithelium; Extracellular Matrix; Future; Goals; Healed; Health; Hydrogels; Immune response; Immune system; Immunologist; Implant; In Vitro; Individual; Institution; Investigation; Laboratories; Lead; Length; Ligands; Ligation; Literature; Mechanics; Natural regeneration; Organ; Outcomes Research; Pattern; Peptides; Performance; Process; Property; Prosthesis; Proteins; Public Health; Research; Research Personnel; Route; Series; Signal Transduction; Site; Skin Substitutes; Spatial Distribution; Specific qualifier value; Stimulus; Surface; Surgeon; System; Tertiary Protein Structure; Therapeutic; Time; Tissue Engineering; Tissues; Translations; Vascular Graft; Work; base; behavior influence; cell behavior; cell growth; chemical property; clinical application; design; healing; immunogenic; immunogenicity; immunoreactivity; implant coating; implant material; implantable device; improved; in vivo; innovation; mimicry; nanometer; nanoscale; nanostructured; protein aminoacid sequence; receptor; regenerative; research study; scaffold; self assembly; success; urologic; viscoelasticity

DESCRIPTION (provided by applicant): Many implanted biomaterials, including vascular grafts, corneal prostheses, urological prostheses, and cultured skin substitutes, function at tissue interfaces that would normally be lined with epithelia or endothelia. However, in most cases these devices do not adequately support the formation of epithelia or endothelia on their surfaces, making them prone to a host of complications including thrombogenesis, immunoreactivity, disregulation of cell growth around them, or poor barrier function. The long-term goal of this research is to develop coatings for implanted biomaterials capable of supporting the formation of functional epithelia and endothelia by mimicking the construction of their native substrates, basement membranes (BMs). BMs are exquisitely tailored protein architectures, and many signaling domains, peptide sequences, mechanical factors, and spatial patterns of ligands have been identified in them that influence the behavior of the epithelia and endothelia they support. However, integrating and tuning this complexity of multiple factors reliably in synthetic biomaterials coatings is currently challenging. The objective of this research is to design biomaterials coatings based on modular peptide co-assembly allowing the incorporation, adjustment, and optimization of many of these factors so as to elicit rapid and functional epithelialization or endothelialization. In addition, steps will be taken to avoid any potentially immunogenic combinations of peptides. The work is divided into four aims: Aim 1) Design a modular system of self-assembling peptides and protein domains where ligand identity, ligand clustering, and viscoelasticity can be independently and precisely adjusted; Aim 2) Identify any peptides or combinations of peptides that significantly raise the immunogenicity of the synthetic BMs; Aim 3) Using factorial experimentation, identify combinations of ligands, viscoelastic moduli, and spatial arrangements of ligands that lead to functional epithelialization and endothelialization; Aim 4) Apply synthetic BMs to existing biomaterials and re-evaluate epithelialization and endothelialization in vitro. This work will be accomplished by a collaborative team of engineers, immunologists, cell biologists, biophysicists, and surgeons by designing and investigating a series of peptides and protein domains capable of co-assembling into precisely defined hydrogels with independent control over ligand identity, ligand clustering on the nanoscale and micron-scale, and matrix viscoelasticity. Experimentally optimized coatings will be applied to commonly used ePTFE and collagen implant materials. The outcomes of this research will include coated prostheses that can be evaluated in large animal models in future investigations, as well as a self-assembling set of peptides that may additionally be useful for a variety of other biomedical applications, including 3-D cell culture or controlled therapeutic release. PUBLIC HEALTH RELEVANCE: This research will positively affect public health by introducing optimally tuned biomaterials coatings capable of supporting the rapid regeneration of epithelia and endothelia on synthetic surfaces, which in turn will result in the enhanced performance of implanted devices such as vascular prostheses, corneal implants, cultured skin substitutes, and other tissue engineered constructs.

描述（由申请人提供）：许多植入的生物材料，包括血管移植物，角膜假体，泌尿科假体和培养的皮肤替代品，在组织界面的功能通常衬有上皮或内皮层。但是，在大多数情况下，这些设备不能充分支持表面上上皮或内皮的形成，使它们容易出现许多并发症，包括血栓形成，免疫反应性，疏离周围的细胞生长或障碍功能不佳。这项研究的长期目标是开发植入的生物材料涂料，能够通过模仿其天然基质基质基底膜（BMS）来支持功能性上皮和内皮的形成。 BMS是精美定制的蛋白质体系结构，并且已经鉴定出了许多信号传导域，肽序列，机械因子和配体的空间模式，它们在其中影响了它们支持的上皮和内皮的行为。但是，在合成生物材料涂料中可靠地整合和调整多种因素的复杂性目前具有挑战性。这项研究的目的是设计基于模块化肽共组装的生物材料涂料，从而允许对许多因素进行整合，调整和优化，从而引起快速和功能性上皮化或内皮化。此外，将采取步骤避免肽的任何潜在免疫原性组合。该作品分为四个目标：目标1）设计一个自组装肽和蛋白质结构域的模块化系统，其中配体身份，配体聚类和粘弹性可以独立和精确调整；目标2）确定明显提高合成BMS免疫原性的肽的任何肽或组合；目标3）使用阶乘实验，确定配体的组合，粘弹性模量以及导致功能性上皮化和内皮化的配体的空间排列；目标4）将合成BMS应用于现有的生物材料，并在体外重新评估上皮化和内皮化。 This work will be accomplished by a collaborative team of engineers, immunologists, cell biologists, biophysicists, and surgeons by designing and investigating a series of peptides and protein domains capable of co-assembling into precisely defined hydrogels with independent control over ligand identity, ligand clustering on the nanoscale and micron-scale, and matrix viscoelasticity.实验优化的涂料将应用于常用的EPTFE和胶原蛋白植入物材料。这项研究的结果将包括涂层的假体，这些假体可以在未来的研究中在大型动物模型中进行评估，以及一组自组装的肽，这些肽可能对其他各种其他生物医学应用也有用，包括3-D细胞培养或受控治疗性治疗。 PUBLIC HEALTH RELEVANCE: This research will positively affect public health by introducing optimally tuned biomaterials coatings capable of supporting the rapid regeneration of epithelia and endothelia on synthetic surfaces, which in turn will result in the enhanced performance of implanted devices such as vascular prostheses, corneal implants, cultured skin substitutes, and other tissue engineered constructs.