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 以及由截然不同的组织类型组成的结构的工程。当前的方法是就业 生物相容性的天然粘合剂，例如纤维蛋白胶。但是，使用这种粘合剂，粘合强度为 身体状况不足，并且会随着时间的流逝而松动。而且，由于它们是额外的 两种组织之间的层/材料，组织之间的健康细胞通信将被干扰 对界面组织发育的不利影响。 在这个项目中，我们提出了一种新的软/硬组织广告的方法，该方法涉及以上两个 缺点。我们将在口服粘膜/骨粘合剂中优化并应用我们的技术以开发设计的 骨粘膜复合物是包含广泛不同组织的构建体的关键例子。 我们提出的方法依赖于将粘合官能团的原位掺入到含细胞的软脚手架中 基于一种生物相容性方法，该方法很容易粘附在表面处理的硬支架上。更多的 具体而言，可将可光的明胶基质基质封装的细胞将被酶促处理为 奎因酮官能团可以与多碳酸酯键上的胺基组形成共价键 脚手架。界面粘附将基于迈克尔反应。 我们声称这项新技术比当前方法具有三个主要优势：1）直接整合了两个 软/硬组织的隔室无需使用第三种材料。 2）粘合剂非常 坚强，不会随着时间的流逝而减少。 3）公式将导致细胞的深度穿透和 脚手架内部的细胞生长增强。 为了检查我们的假设，粘合强度将在定量和定性上进行全面评估 随着时间的流逝，将检查骨粘膜络合物复合物和生物学特征 详细。通过纤维蛋白胶处理为粘合剂的类似构建体将平行生产以使用 作为对照样本。此外，将我们的骨粘膜结构的粘合力与 刚被屠杀的猪的下颌中的天然口服粘膜/骨界面组织。 骨粘膜络合物中提出的粘附方法的成功结果将表明 可以（在相关修改之后）应用技术来进行界面时机的工程 牙周复合物，骨/软骨，骨/韧带，骨/肌腱和牙本质/牙髓络合物。 开发的骨粘膜复合物的应用包括a）临床移植，例如肺泡 重建和口腔内移植，b）产生临床相关的体外测试系统和替代方案 至1）研究生物材料和口腔组织相互作用的动物测试模型，以及2）口腔疾病筛查 和药物输送系统的评估。