Tendinopathy is a common musculoskeletal disorder in which a significant number of patients do not attain effective therapeutic outcomes. The extent of the inflammatory response and the dynamics of collagen synthesis metabolism are critical factors that influence the intrinsic self-repair capacity of tendons. However, the poor microenvironment within the tendon significantly impedes the self-repair process in tendinopathy. In this study, an injectable tendon-derived decellularized extracellular matrix (tdECM) hydrogel was utilized to treat tendinopathy. This hydrogel provides a more cytocompatible microenvironment while retaining certain bioactive factors of native tendon extracellular matrix (ECM), compared to collagen hydrogel. Notably, it was discovered for the first time that the tdECM hydrogel promotes M2 macrophage polarization, thereby exerting an anti-inflammatory effect in vivo. Furthermore, utilizing tdECM as a carrier for the sustained release of tendon-derived stem cells exosomes (TDSCs-Exos), our findings from both in vitro and in vivo studies indicate that the tdECM hydrogel, in conjunction with exosomes, demonstrated a pronounced synergistic enhancement in modulating inflammation, promoting M2 macrophage polarization, and facilitating tendon regeneration and repair efficacy. These results suggest its potential as a promising therapeutic strategy for tendon disorders.

Acute pancreatitis (AP) is a severe inflammatory disorder of the pancreas, characterized by high morbidity and mortality rates. Despite significant advancements in understanding the pathophysiological mechanisms of AP, current treatment options still face considerable limitations. Recent studies have underscored the therapeutic potential of quercetin, a natural flavonoid, due to its potent antioxidant, anti-inflammatory, and immunomodulatory properties, positioning it as a promising therapeutic candidate for AP. This review explores the effects of quercetin on AP, highlighting its antioxidant activities, its role in immune modulation, and its protective effects on pancreatic tissue. Furthermore, it examines quercetin’s multi-target mechanisms and its advantages over conventional therapies, such as N-acetylcysteine and corticosteroids. Although preliminary studies suggest that quercetin can alleviate inflammation and oxidative stress in AP, clinical evidence remains limited. One of the main challenges for quercetin’s clinical application is its low bioavailability. Future research should focus on strategies to enhance its bioavailability and on conducting large-scale randomized controlled trials to more comprehensively assess its efficacy and safety in the treatment of AP.

Tendon-related diseases (TRDs) are increasingly common in the current aging society and impose a significant burden on patients. Despite therapeutic advances, the pathophysiology of TRDs remains poorly understood, hindering effective clinical management. The macrophages are highly plastic immune cells involved in the maintenance of in vivo homeostasis and the injury-healing process. Their dual role in TRDs has been widely investigated, either promoting tenogenic and chondrogenic differentiation or amplifying inflammatory response, underscoring their therapeutic potential for TRDs treatment. Therefore, the review aims to summarize the roles of macrophages in the healing of TRDs, characterized by limited regenerative capacity, and examine strategies for the modulation of macrophage phenotypes to accelerate the regeneration process. Finally, we review applications involving macrophage modulation within the context of tissue engineering of TRDs, providing novel insights for the design of biomaterials-based targeted delivery systems.

Osteoporosis, an age-related metabolic bone disease, is mainly caused by an imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. At present, there are many osteoporosis drugs that can promote bone formation or inhibit bone resorption. However, there were few therapeutic drugs that can simultaneously promote bone formation and inhibit bone resorption. Oridonin (ORI), a tetracyclic diterpenoid compound isolated from Rabdosia rubescens, has been proved to have anti-inflammatory, anti-tumor effects. However, little is known about the osteoprotective effect of oridonin. Thioacetamide (TAA) is a common organic compound with significant hepatotoxicity. Recent studies have found that there was a certain association between TAA and bone injury. In this work, we investigated the effect and mechanism of ORI on TAA-induced osteoclastogenesis and inhibition of osteoblast differentiation. The results showed that TAA could promote the osteoclastogenesis of RAW264.7 by promoting the MAPK/NF-κB pathway, and also promoted p65 nuclear translocation and activated intracellular ROS generation, and ORI can inhibit these effects to inhibit TAA-induced osteoclastogenesis. Moreover, ORI can also promote the osteogenic differentiation pathway and inhibit adipogenic differentiation of BMSCs to promote bone formation. In conclusion, our results revealed that ORI, as a potential therapeutic drug for osteoporosis, could protect against TAA-induced bone loss and TAA-inhibited bone formation.

Tendon injuries often lead to joint dysfunction due to the limited self-regeneration capacity of tendons. Repairing tendons is a major challenge for surgeons and imposes a significant financial burden on society. Therefore, there is an urgent need to develop effective strategies for repairing injured tendons. Tendon tissue engineering using hydrogels has emerged as a promising approach that has attracted considerable interest. Hydrogels possess excellent biocompatibility and biodegradability, enabling them to create an extracellular matrix-like growth environment for cells. They can also serve as a carrier for cells or other substances to accelerate tendon repair. In the past decade, numerous studies have made significant progress in the preparation of hydrogel scaffolds for tendon healing. This review aims to provide an overview of recent research on the materials of hydrogel-based scaffolds used for tendon tissue engineering and discusses the delivery systems based on them.