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.

最严重的颞下颌关节紊乱病例包括下颌髁突退行性变。 不幸的是，不存在再生选择，并且当前的治疗无法恢复全部功能。 髁突的关节组织是纤维软骨，由复杂的界面组成 纤维组织、软骨组织和骨组织之间的结构，对于正常功能至关重要，即 因严重的颞下颌关节紊乱而丧失。本研究的目的是再生纤维软骨骨 使用综合组织观察骨骼成熟山羊的下颌骨髁界面 工程方法。新型多层支架植入物将治疗髁突缺损 旨在促进特定部位的组织再生。我们拥有强大的体内试验数据 显示我们的支架组件可以在我们的新型山羊中再生纤维和软骨组织 模型和节段缺损模型中的骨骼。我们将把支架植入内侧 树林状髁突缺损。我们假设多层支架将允许现场 下颌骨髁突软骨的特异性纤维软骨骨再生比较 均质海绵支架和未经处理的对照缺陷。首先，我们将研究 体外多层支架设计的特性。我们将表征渗透性和 TGFβ从支架中释放。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 使用 1、3 和 6 的终端测定进行组织成分和髁结构形成 手术后几个月。第三，我们将研究三种细胞亚群的再生潜力 发现于髁突上。成功完成该提案是提供一个关键的步骤 再生疗法治疗TMJ下颌软骨退变，并为成功奠定基础 其他部位的骨软骨组织再生。