Biomimetic Intrafibrillar Mineralization of Native Tendon for Soft-Hard Interface Integration by Infiltration of Amorphous Calcium Phosphate Precursors.

Soft and hard tissues possess distinct biological properties. Integrating the soft-hard interface is difficult due to the inherent non-osteogenesis of soft tissue, especially of anterior cruciate ligament and rotator cuff reconstruction. This property makes it difficult for tendons to be mineralized and integrated with bone in vivo. To overcome this challenge, a biomimetic mineralization strategy is employed to engineer mineralized tendons. The strategy involved infiltrating amorphous calcium phosphate precursors into collagen fibrils, resulting in hydroxyapatite deposition along the c-axis. The mineralized tendon presented characteristics similar to bone tissue and induced osteogenic differentiation of mesenchymal stem cells. Additionally, the interface between the newly formed bone and tendon is serrated, suggesting a superb integration between the two tissues. This strategy allows for biomineralization of tendon collagen and replicating the hallmarks of the bone matrix and extracellular niche, including nanostructure and inherent osteoinductive properties, ultimately facilitating the integration of soft and hard tissues.

Stem cell-based therapeutic strategies for rotator cuff tendinopathy.

Rotator cuff tendinopathy is a common musculoskeletal disorder that imposes significant health and economic burden. Stem cell therapy has brought hope for tendon healing in patients with final stage rotator cuff tendinopathy. Some clinical trials have confirmed the effectiveness of stem cell therapy for rotator cuff tendinopathy, but its application has not been promoted and approved. There are still many issues that should be solved prior to using stem cell therapy in clinical applications. The optimal source and dose of stem cells for rotator cuff tendinopathy should be determined. We also proposed novel prospective approaches that can overcome cell population heterogeneity and standardize patient types for stem cell applications. The translational potential of this article: This review explores the optimal sources of stem cells for rotator cuff tendinopathy and the principles for selecting stem cell dosages. Key strategies are provided for stem cell population standardization and recipient selection.

Animal model for tendinopathy.

Background: Tendinopathy is a common motor system disease that leads to pain and reduced function. Despite its prevalence, our mechanistic understanding is incomplete, leading to limited efficacy of treatment options. Animal models contribute significantly to our understanding of tendinopathy and some therapeutic options. However, the inadequacies of animal models are also evident, largely due to differences in anatomical structure and the complexity of human tendinopathy. Different animal models reproduce different aspects of human tendinopathy and are therefore suitable for different scenarios. This review aims to summarize the existing animal models of tendinopathy and to determine the situations in which each model is appropriate for use, including exploring disease mechanisms and evaluating therapeutic effects. Methods: We reviewed relevant literature in the PubMed database from January 2000 to December 2022 using the specific terms ((tendinopathy) OR (tendinitis)) AND (model) AND ((mice) OR (rat) OR (rabbit) OR (lapin) OR (dog) OR (canine) OR (sheep) OR (goat) OR (horse) OR (equine) OR (pig) OR (swine) OR (primate)). This review summarized different methods for establishing animal models of tendinopathy and classified them according to the pathogenesis they simulate. We then discussed the advantages and disadvantages of each model, and based on this, identified the situations in which each model was suitable for application. Results: For studies that aim to study the pathophysiology of tendinopathy, naturally occurring models, treadmill models, subacromial impingement models and metabolic models are ideal. They are closest to the natural process of tendinopathy in humans. For studies that aim to evaluate the efficacy of possible treatments, the selection should be made according to the pathogenesis simulated by the modeling method. Existing tendinopathy models can be classified into six types according to the pathogenesis they simulate: extracellular matrix synthesis-decomposition imbalance, inflammation, oxidative stress, metabolic disorder, traumatism and mechanical load. Conclusions: The critical factor affecting the translational value of research results is whether the selected model is matched with the research purpose. There is no single optimal model for inducing tendinopathy, and researchers must select the model that is most appropriate for the study they are conducting. The translational potential of this article: The critical factor affecting the translational value of research results is whether the animal model used is compatible with the research purpose. This paper provides a rationale and practical guide for the establishment and selection of animal models of tendinopathy, which is helpful to improve the clinical transformation ability of existing models and develop new models.