Development of an Integrated 3D Human Osteo-Mucosal Model

集成 3D 人体骨粘膜模型的开发

• 批准号: 10224467
• 负责人: Lobat Tayebi
• 金额: $ 7.84万
• 依托单位: MARQUETTE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224467
• 关键词: 3-Dimensional; 3D Print; Address; Adhesions; Adhesives; Air; Alveolar; Amines; Animal Model; Animal Testing; Area; Basement membrane; Biocompatible Materials; Biologic Characteristic; Biological; Biological Assay; Bioreactors; Bone Morphogenetic Proteins; Bone Tissue; Cartilage; Cell-Matrix Junction; Cells; Chemicals; Clinical; Collagen; Communication; Complex; Connective Tissue; Cytokeratin; Data; Defect; Dental Materials; Dental Pulp; Dentin; Desmosomes; Development; Drug Delivery Systems; Drug Evaluation; Employment; Encapsulated; Engineering; Epithelial; Epithelium; Family suidae; Fibrin Tissue Adhesive; Fibroblasts; Formulation; Future; Gelatin; Glues; Growth; Healthcare; Histology; Human; Immunohistochemistry; Implant; In Situ; In Vitro; Incubated; Jaw; Laboratories; Ligaments; Liquid substance; Metabolic; Methacrylates; Methods; Modeling; Modification; Monitor; Monophenol Monooxygenase; Mouth Diseases; Mucous Membrane; Natural regeneration; Nutrient; Oral; Oral Surgical Procedures; Oral health; Oral mucous membrane structure; Osteoblasts; Osteocalcin; Outcome; Penetration; Physiological; Printing; Procedures; Production; Property; Quinones; Reaction; Sampling; Side; Structure; Surface; System; Techniques; Tendon structure; Testing; Thick; Time; Tissue Engineering; Tissue Viability; Tissues; Transmission Electron Microscopy; Transplantation; base; biomaterial compatibility; bone; cell growth; clinically relevant; covalent bond; decorin; design; functional group; improved; in vitro Model; in vitro testing; in vivo; in vivo Model; interfacial; keratinocyte; novel; novel strategies; oral tissue; polycaprolactone; reconstruction; scaffold; screening; soft tissue; three-dimensional modeling; time interval; tricalcium phosphate

SUMMARY: The integration and stability of the hard/soft tissue interface is a major challenge in regeneration and engineering of constructs composed of widely different tissue types. The current approach is employment of biocompatible natural adhesives, such as fibrin glue. However, using such adhesives, the adhesion strength is not strong enough in physiological condition and will loosen in time. Moreover, since they act as an additional layer/material between two tissues, the healthy cellular communication between tissues will be disturbed with adverse influence on interfacial tissue development. In this project, we propose a new method for adhesion of soft/hard tissues, which addresses both of the above drawbacks. We will optimize and apply our technique in oral mucosa/bone adhesion to develop an engineered osteo-mucosal complex as a key example of a construct containing widely dissimilar tissues. Our proposed approach relies on in situ incorporation of adhesive functional groups into a cell-laden soft scaffold based on a biocompatible method, which become readily adherent to a surface treated hard scaffold. More specifically, the photocurable gelatin-based matrix encapsulating cells will be enzymatically treated to have quinone functional groups which can form covalent bonds with the amine groups on the polycaprolactone bone scaffold. The interfacial adhesion will be based on Michael reaction. We claim that this new technique has three major advantages over current methods: 1) It directly integrates two compartments of soft/hard tissues without the need for employing a third material. 2) The adhesion is very strong and will not be diminished over time. 3) The formulation will lead to in depth penetration of cells and enhanced cell growth inside the scaffolds. To examine our hypotheses, the adhesion strength will be fully evaluated in vitro quantitatively and qualitatively over time after development of the osteo-mucosal complex, and the biological characteristics will be inspected in detail. A similar construct treated by fibrin glue as the adhesive agent will be produced in parallel to be used as the control sample. Moreover, the adhesion strength of our osteo-mucosal construct will be compared with the natural oral mucosa/bone interfacial tissue in a freshly slaughtered pig’s jaw. A successful outcome from the proposed adhesion method in the osteo-mucosal complex will suggest that the technique can potentially be applied (after relevant modifications) for engineering of interfacial tissues in periodontal complex, bone/cartilage, bone/ligament, bone/tendon, and dentin/pulp complexes. The applications of the developed osteo-mucosa complex include A) clinical transplantation such as alveolar reconstruction and intraoral grafting, B) production of a clinically relevant in vitro test system and an alternative to animal test models for 1) studying the interaction of biomaterials and oral tissue, and 2) oral disease screening and evaluation of drug delivery systems.

摘要：硬/软组织界面的整合和稳定性是再生的主要挑战 以及由广泛不同的组织类型组成的构建体的工程。目前的做法是采用 生物相容性天然粘合剂，例如纤维蛋白胶。然而，使用这种粘合剂，粘合强度是 生理状态下强度不够，时间一长就会松动。此外，由于它们充当额外的 两个组织之间的层/材料，组织之间的健康细胞通讯将受到干扰 对界面组织发育产生不良影响。 在这个项目中，我们提出了一种软/硬组织粘合的新方法，它解决了上述两个问题 缺点。我们将优化并应用我们的口腔粘膜/骨粘附技术来开发工程化的 骨粘膜复合体是包含广泛不同组织的构造的一个关键例子。 我们提出的方法依赖于将粘合官能团原位纳入充满细胞的软支架中 基于生物相容性方法，它很容易粘附到表面处理过的硬支架上。更多的 具体来说，光固化明胶基基质封装细胞将经过酶处理，以具有 醌官能团可与聚己内酯骨上的胺基形成共价键 脚手架。界面粘附将基于迈克尔反应。 我们声称这种新技术与现有方法相比具有三个主要优点：1）它直接集成了两种方法 软/硬组织隔室，无需使用第三种材料。 2）附着力非常强 强大且不会随着时间的推移而减弱。 3) 配方会深入渗透细胞， 增强支架内的细胞生长。 为了检验我们的假设，将在体外定量和定性地全面评估粘附强度 骨粘膜复合体发育后随时间推移，将检查其生物学特性 详细。将并行生产以纤维蛋白胶作为粘合剂处理的类似结构以供使用 作为对照样本。此外，我们的骨粘膜结构的粘附强度将与 新鲜屠宰的猪下巴中的天然口腔粘膜/骨界面组织。 所提出的骨粘膜复合体粘附方法的成功结果表明， 该技术有可能（经过相关修改后）应用于界面组织工程 牙周复合体、骨/软骨、骨/韧带、骨/肌腱和牙本质/牙髓复合体。 所开发的骨粘膜复合体的应用包括A)临床移植如牙槽骨 重建和口内移植，B) 生产临床相关的体外测试系统和替代方案 动物测试模型用于 1) 研究生物材料和口腔组织的相互作用，以及 2) 口腔疾病筛查 和药物输送系统的评价。