Biomolecule releasing adhesive for cell-mediated labral repair

用于细胞介导的盂唇修复的生物分子释放粘合剂

• 批准号: 10736334
• 负责人: Liping Tang
• 金额: $ 41.87万
• 依托单位: UNIVERSITY OF TEXAS ARLINGTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10736334
• 关键词: 3-Dimensional; Acceleration; Acute; Address; Adhesions; Adhesives; Animal Model; Anterior; Binding; Cartilage; Cell Separation; Cell Therapy; Cells; Chemistry; Chitosan; Complement; Complementary therapies; Cyclooctenes; Effectiveness; Engineering; Extracellular Matrix; Extracellular Matrix Proteins; Fibrin Tissue Adhesive; Fibrocartilages; Gel; Growth Factor; Histocompatibility; Human; Hydrogels; In Situ; In Vitro; Infiltration; Inflammation; Inflammatory; Inflammatory Infiltrate; Inflammatory Response; Injectable; Injections; Injury; Intervention; Investigation; Joint structure of shoulder region; Knowledge; Laboratories; Lesion; Literature; Location; Mediating; Methods; Modeling; Morphology; Muscle; Natural regeneration; Needles; Operative Surgical Procedures; Outcome; Pain; Physical therapy; Platelet-Derived Growth Factor; Process; Production; Proliferating; Property; Publishing; Rattus; Recovery of Function; Recurrence; Reporting; Residual state; Rotator Cuff; Series; Shoulder; Site; Source; Structure; Surgical sutures; System; Technology; Testing; Time; Tissue Engineering; Tissue Model; Tissues; Work; bone; bone healing; cell motility; chronic shoulder pain; clinical translation; cytotoxicity; design; disability; healing; implantation; improved; in vivo; in vivo regeneration; injured; migration; novel; novel therapeutic intervention; progenitor; recruit; regenerative; regenerative cell; regenerative tissue; release factor; repaired; response; scaffold; seal; stem cells; tissue injury; tissue regeneration

Summary The glenoid labrum is a fibrocartilaginous structure that lines the edge of the glenoid rim of the shoulder joint. Glenoid labral tears, or lesions, can occur in several distinct locations (anterior, superior, or posterior) with variable morphology (detachment from bone or intrasubstance) and have been associated with chronic shoulder pain and/or instability. While operative intervention is typically needed to re-attach the damaged labrum to the glenoid bone or to directly repair an intrasubstance tear of the labrum, recurrent shoulder instability and pain following surgical repair of the labrum has been reported to be as high as 30%. This continued disability following treatment is consistent with the poor healing capacity of the labrum. Current labral repair typically involves the use of anchors and sutures to restore stability of the labrum and shoulder, but rarely promotes actual regeneration of the injured labrum. Although cell therapy and tissue engineering approaches have been used to improve cartilage and bone healing, these approaches have not been explored to improve glenoid labrum healing. To address this deficiency in the treatment of glenoid labral injuries, it is essential to improve our knowledge of the process of labral tear associated tissue injury and to develop a new treatment method assisting in labral tissue regeneration and functional recovery. In our laboratory, substantial progress has been made on this front. Briefly, click-chemistry based adhesives have been synthesized and these adhesives possess good tissue attachment, cell/tissue compatibility, and in situ growth factor releasing property. Equally important, our studies have uncovered an abundant source of progenitor cells in human and rat labrum tissue, which can be recruited to the injured sites and stimulated to produce abundant extracellular matrix protein for accelerated labrum healing. When evaluated in an in vivo glenoid labrum tear rat model, the application of bioadhesive alone suffices to reduce 90% inflammatory cell infiltration and ~70% labral tissue erosion. By eliciting progenitor cell responses (recruitment, proliferation, and ECM production), the application of growth factor-releasing adhesive scaffold was found to enhance labral healing (with complete labral tear regeneration by 6 weeks vs. 50% labral degeneration/lost in no treatment control). These exciting findings support two hypotheses. First, an adhesive can be fabricated to serve as a scaffold matrix to bridge and seal the gap within the torn labrum, and preferentially recruit and stimulate endogenous labral progenitor cells to the injury site for repairing and regenerating damaged labral tissue. Second, labral tear injury mediated synovial inflammatory responses and infiltration of inflammatory cells in and around the tear site cause labral tissue erosion. These hypotheses will be investigated through 3- series of studies. The successful completion of the proposed work will significantly improve our understanding of labral tear-associated tissue damage and lead to the creation of a new treatment approach for promoting labrum regeneration complementing current surgical labral repair of torn labrum with suture anchor strategies.

总结 关节盂唇是一种纤维软骨结构，排列在肩关节的关节盂边缘。 关节盂唇撕裂或病变可能发生在几个不同的位置（前部、上级或后部）， 形态学变化（从骨上或物质内脱离），并与慢性肩关节相关 疼痛和/或不稳定。虽然通常需要手术干预以将受损的唇重新附接到唇上， 关节盂骨或直接修复盂唇的实质性撕裂、复发性肩关节不稳定和疼痛 据报道，在唇的手术修复之后，这种持续的残疾， 治疗与唇的不良愈合能力一致。目前的唇修复通常涉及 使用锚钉和缝线恢复盂唇和肩关节的稳定性，但很少促进实际的 修复受伤的上唇。尽管细胞疗法和组织工程方法已经用于 虽然这些方法可以改善软骨和骨愈合，但是还没有研究这些方法来改善关节盂唇愈合。 为了解决盂唇损伤治疗中的这一缺陷，有必要提高我们对以下方面的认识： 唇撕裂相关组织损伤的过程，并开发一种新的治疗方法， 组织再生和功能恢复。在我们的实验室里，在这方面已经取得了实质性的进展。 简单地说，已经合成了基于点击化学的粘合剂，并且这些粘合剂具有良好的组织， 附着、细胞/组织相容性和原位生长因子释放特性。同样重要的是，我们的研究 在人类和大鼠的唇组织中发现了丰富的祖细胞来源， 并刺激产生丰富的细胞外基质蛋白，加速唇愈合。 当在体内盂唇撕裂大鼠模型中进行评价时，单独应用生物粘合剂足以 减少90%的炎性细胞浸润和~70%的唇组织侵蚀。通过引发祖细胞反应 （募集，增殖和ECM产生），应用生长因子释放粘附支架， 发现可促进唇愈合（6周时唇撕裂完全再生，而唇撕裂再生率为50% 变性/在无处理对照中丢失）。这些令人兴奋的发现支持了两个假设。首先，粘合剂 以桥接和密封撕裂的唇内的差距，并且优选地 募集和刺激内源性唇祖细胞到损伤部位，用于修复和再生受损的 唇组织第二，盂唇撕裂损伤介导的滑膜炎症反应和炎性细胞浸润， 撕裂部位内和周围的细胞引起唇组织侵蚀。这些假设将通过3- 系列讲话成功完成拟议的工作将大大提高我们的认识 唇撕裂相关的组织损伤，并导致创造一种新的治疗方法， 盂唇再生补充了目前使用缝合锚策略对撕裂盂唇进行的手术盂唇修复。