Polymer Scaffolds for Mandibular Condyle Cartilage Regeneration

用于下颌髁软骨再生的聚合物支架

• 批准号: 10523734
• 负责人: Alejandro Jose Almarza
• 金额: $ 8.27万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10523734
• 关键词: 4 year old; Adult; Architecture; BMP2 gene; Bilateral; Binding; Biochemical; Biocompatible Materials; Biological Assay; Biological Availability; Bone Regeneration; Cartilage; Cells; Chondrocytes; Chondrogenesis; Data; Defect; Diffusion; Family suidae; Fibroblasts; Fibrocartilages; Functional Regeneration; Gelatin; Goat; Growth; Heparin; Heparin Binding; Hyaline Cartilage; Hydrogels; Implant; In Vitro; Infiltration; Injury; Kinetics; Liquid substance; Mandible; Mandibular Condyle; Mandibular Scaffold; Miniature Swine; Modeling; Nanoporous; Natural regeneration; Operative Surgical Procedures; Osteogenesis; Pain; Pathology; Patients; Perfusion; Periodicity; Permeability; Phenotype; Polymers; Population; Porifera; Property; Publishing; Regenerative research; Replacement Arthroplasty; Site; Technology; Temporomandibular Joint; Temporomandibular Joint Disorders; Time; Tissue Engineering; Tissues; Transforming Growth Factor beta; articular cartilage; base; bioscaffold; bone; cartilage degradation; cartilage regeneration; cartilaginous; clinically relevant; condylar cartilage; costal cartilage; design; ethylene glycol; fibula; healing; implant design; in vivo; in vivo regeneration; mechanical load; mechanical properties; migration; novel; osteochondral tissue; osteoprogenitor cell; prevent; progenitor; regeneration potential; regenerative; regenerative therapy; regenerative treatment; scaffold; skeletal; stem cells; subchondral bone; tissue regeneration; treatment effect

The most severe cases of TMJ disorders consist of mandibular condyle degeneration. Unfortunately, no regenerative options exists and current treatments do not restore full function. The articulating tissue of the condyle is a fibrocartilage that consists of an intricate interface between fibrous, cartilaginous, and boney tissue that is essential for normal function and that is lost in severe TMJ disorders. The objective of this study is to regenerate fibrocartilage-bone interface of the mandibular condyle in skeletally mature goats using a comprehensive tissue engineering approach. A condylar defect will be treated with novel multilayer scaffold implant designed to promote site-specific tissue regeneration. We have strong pilot in-vivo data showing that our scaffolds components regenerate fibrous and cartilage tissue in our novel goat model, and bone in a segmental defect model. We will implant the scaffolds in a mediolateral grove-shaped condylar defect. We hypothesize that a multilayer scaffold will allow for site- specific fibrous-cartilage-bone regeneration of the mandibular condyle cartilage when compared to a homogenous sponge scaffold and untreated control defects. First, we will study the properties of a multilayer scaffold design in-vitro. We will characterize the permeability and release of TGFβs from the scaffold. Second, we will assess the functional healing of condylar defects treated with the multilayer scaffolds. We will assess mechanical properties, regenerate tissue composition, and condylar architecture formation using terminal assays at 1, 3 and 6 months post-surgery. Third, we will study the regeneration potential of three cell subpopulations found on the condyle. Successful completion of this proposal is the critical step to provide a regenerative therapy to treat TMJ mandibular cartilage degeneration, and a basis for successful osteochondral tissue regeneration in other sites.

最严重的TMJ疾病包括下颌骨髁状突变性。 不幸的是，没有再生的选择，目前的治疗方法不能完全恢复功能。 髁状突的关节组织是由复杂的界面组成的纤维软骨。 在纤维、软骨和骨组织之间，是正常功能所必需的，也就是 迷失在严重的TMJ障碍中。本研究的目的是再生纤维软骨-骨。 骨性成熟山羊下颌骨髁突界面的综合组织学研究 工程学方法。新型多层支架植入物修复髁状突骨缺损 旨在促进特定部位的组织再生。我们有强大的飞行员体内数据 显示我们的支架成分在我们的新山羊体内再生纤维和软骨组织 模型，以及节段性缺损模型中的骨。我们会将支架植入内侧 格罗夫状的髁状突骨缺。我们假设多层脚手架将允许场地- 下颌骨髁突软骨特异性纤维-软骨-骨再生的比较 至同质海绵支架和未经处理的对照缺陷。首先，我们将研究 体外设计的多层支架的性能。我们将表征渗透性和 释放转化生长因子βS的脚手架。其次，我们将评估髁突的功能愈合情况。 用多层支架处理的缺陷。我们将评估机械性能，再生 在1、3和6使用末端分析的组织成分和髁状突构型形成 手术后几个月。第三，我们将研究三个细胞亚群的再生潜力 在髁状突上发现的。成功完成这项提案是提供 再生疗法治疗TMJ下颌骨软骨退行性变，并为成功奠定基础 其他部位的骨软骨组织再生。