Tendon-Bone Junction Organoids: Construction and Application.

Abstract

The mechanism of tendon-bone healing is highly complex and multifaceted, being influenced by a wide range of factors that can determine the healing outcome. In the past two decades, a variety of therapeutic approaches have been explored and refined to enhance tendon-bone healing. Organoid culture technology, which has emerged as a cutting-edge research tool, involves the creation of three-dimensional tissues that can self-renew and self-organize, closely mimicking the spatial characteristics of natural biological structures. Integrating existing therapeutic strategies into the development of tendon-bone junction organoids offers a highly promising approach for accurately simulating the tendon-bone junction. Therefore, this review first clarifies the anatomical structure of the tendon-bone junction and the detailed process of tendon-bone healing. Then, the latest application of treatment strategies aimed at promoting tendon-bone healing is highlighted. These approaches include cell-based therapies, cell-derived approaches, biomimetic scaffolds, and external stimulations. This review provides a comprehensive overview and discusses potential applications and future challenges of biomaterials in the development of tendon-bone junction organoids. With the continuous advancement of organoid technology, these therapeutic strategies are expected to emerge as powerful tools for enhancing tendon-bone healing. STATEMENT OF SIGNIFICANCE: Despite extensive exploration of various therapeutic strategies, the clinical outcomes of tendon-bone healing remain suboptimal and unpredictable. This is largely due to the highly complex and multifaceted nature of the healing process, which existing experimental models fail to fully recapitulate. Therefore, a robust platform is needed to model the native tendon-bone junction and evaluate combination therapies. Tendon-bone junction organoids have emerged as a highly promising approach to meet these requirements. A comprehensive review that systematically bridges the gap between established therapeutic strategies and this innovative organoid technology is currently lacking. This review aims to fulfill this critical need by synthesizing the current knowledge on tendon-bone anatomy, healing mechanisms, and cutting-edge therapies to guide the rational development of biomaterial-enhanced organoids. By providing a foundational framework, this review is expected to accelerate the advancement of more effective and personalized strategies for enhancing tendon-bone repair, ultimately improving the prognosis for countless patients with related injuries.