Due to the spatiotemporal complexity of the composition, structure, and cell population of the tendon-bone interface (TBI), it is difficult to achieve true healing. Recent research is increasingly focusing on engineered exosomes, which are a promising strategy for TBI regeneration. This review discusses the physiological and pathological characteristics of TBI and the application and limitations of natural exosomes in the field of tendon-bone healing. The definition, loading strategies, and spatiotemporal properties of engineered exosomes were elaborated. We also summarize the application and future research directions of engineered exosomes in the field of tendon-bone healing. Engineered exosomes can spatially deliver cargo to targeted sites and temporally realize the sustained release of therapeutic molecules in TBI. This review expounds on the multidifferentiation of engineered exosomes for tendon-bone healing, which effectively improves the biological and biomechanical properties of TBI. Engineered exosomes could be a promising strategy for tendon-bone healing.

The tendon or ligament is attached to the bone by a triphasic but continuous area of heterogeneous tissue called the tendon-bone interface (TBI). The rapid and functional regeneration of TBI is challenging owing to its complex composition and difficulty in self-healing. The development of new technologies, such as decellularization, has shown promise in the regeneration of TBI. Several ex vivo and in vivo studies have shown that decellularized grafts and decellularized biomaterial scaffolds achieved better efficacy in enhancing TBI healing. However further information on the type of review that is available is needed. In this review, we discuss the current application of decellularization biomaterials in promoting TBI healing and the possible mechanisms involved. With this work, we would like to reveal how tissues or biomaterials that have been decellularized can improve tendon-bone healing and to provide a theoretical basis for future related studies. Decellularization is an emerging technology that utilizes various chemical, enzymatic and/or physical strategies to remove cellular components from tissues while retaining the structure and composition of the extracellular matrix (ECM). After decellularization, the cellular components of the tissue that cause an immune response are removed, while various biologically active biofactors are retained. This review further explores how tissues or biomaterials that have been decellularized improve TBI healing.

Tetrahedral framework nucleic acids (tFNAs), a crucial component of DNA nanotechnology, have emerged as versatile tools in biomedical research, largely owing to their distinctive structural features and multifaceted capabilities. Recent studies have highlighted the ability of tFNAs to specifically target biological pathways, facilitate cellular uptake, and enhance therapeutic efficacy. tFNAs also show considerable potential in addressing challenges such as drug resistance and poor bioavailability. However, several challenges, including limited in vivo stability, low drug-loading capacity, and potential long-term toxicity, need to be addressed for successful clinical translation. This review comprehensively explores the latest advancements in tFNAs, focusing particularly on their applications and mechanisms in treating a wide array of diseases. From bone diseases to ophthalmic disorders, tFNAs not only promote bone regeneration but also enhance therapeutic efficacy through targeted drug delivery. They also play a role in combating infectious diseases, skin and soft tissue repair, neurological and mental disorders, hepatorenal diseases, and cancer. In addition, tFNAs have demonstrated significant potential in regenerative medicine, immunomodulation, and gene delivery. This work highlights the future potential of DNA nanotechnology in precision medicine, paving the way for next-generation therapeutic strategies.

Heterotopic Ossification (HO) is a complex and multifactorial pathological process characterized by abnormal bone production in areas outside the skeletal

Tendon injury is a common and frequent disease in the field of sports medicine, and tendon repair after injury is a common clinical difficulty. Repair strategy based on tendon stem cells (TDSCs) therapy is considered a promising therapeutic option for the treatment of tendon injuries. Icariin (ICA) has been shown to be an effective herbal monomer for the treatment of tendon-bone healing and may be effective in the repair of tendon injuries. In vitro, TDSCs isolated from C57 mice were treated with ICA (0.01–100 µM) to assess proliferation (CCK-8 assay) and tendonogenic differentiation (qRT-PCR). In vivo, 42 C57 mice with surgically induced patellar tendon defects were randomized into three groups (n = 14/group): (1) 20 mg/kg ICA, (2) 40 mg/kg ICA, and (3) control group (DMSO), administered intraperitoneally for 14 days. Half of each group (n = 7) underwent histopathological (hematoxylin-eosin staining, Masson staining) and molecular (qRT-PCR) analyses at 2 and 4 weeks post-surgery. In vitro, after 7 days of ICA intervention in TDSC, the expression of Mohawk (MKX), Scleraxis (SCX), fibromodulin (FMOD), and Tenomodulin (TNC) were higher in the ICA group than in the control group. In vivo, the expression of MKX, SCX, FMOD, and TNC was higher in the 20 mg/kg ICA group and 40 mg/kg ICA group than in the control group at 2 and 4 weeks after surgery. Histological evaluation revealed superior tendon repair in both ICA-treated groups compared to controls at both 2 and 4 weeks postoperative intervals. The 20 mg/kg ICA group demonstrated a significant enhancement in tissue continuity and collagen fiber organization, exhibiting greater defect filling, fewer interstitial gaps, and reduced vascular infiltration. In contrast, control specimens exhibited disorganized collagen architecture with prominent interstitial gaps. The 40 mg/kg ICA group showed intermediate repair outcomes between the 20 mg/kg ICA and control groups. ICA can improve tendon injury repair by enhancing tendonogenic differentiation of TDSC.

Type 2 diabetes mellitus (T2DM) is accompanied by pathological alterations in skeletal muscle, yet effective therapeutic strategies targeting these alterations remain limited. Current interventions, including exercise and nutritional supplementation, often exhibit poor long-term adherence and limited efficacy under diabetic conditions. Therefore, convenient, durable, and metabolically effective therapies are urgently needed. Evidence suggests that excessive endoplasmic reticulum (ER) stress and unfolded protein response (UPR) activation contribute to diabetic skeletal muscle remodeling, while pyruvate dehydrogenase kinase 4 (PDK4) may serve as a key mediator linking metabolic dysfunction to ER stress signaling. A T2DM mouse model was established using high-fat diet feeding combined with streptozotocin administration. Inclisiran was administered intraperitoneally after model establishment. RNA sequencing combined with SVM-RFE analysis identified key targets potentially associated with protective effects of inclisiran. Metabolic parameters, muscle atrophy markers, ER stress/UPR signaling, and muscle fiber type transition were evaluated by real-time qPCR, immunoblotting, and immunofluorescence. Inclisiran significantly reduced fasting blood glucose levels and improved metabolic abnormalities in diabetic mice. Transcriptomic analysis identified PDK4 as a key hub gene potentially associated with pathological alterations in diabetic skeletal muscle and the response to inclisiran treatment. Diabetic mice exhibited marked activation of ER stress/UPR signaling and increased expression of FOXO1, PDK4, and FBX32, whereas inclisiran treatment significantly suppressed these alterations. Additionally, inclisiran partially reversed diabetes-induced muscle fiber type transition from oxidative to glycolytic phenotypes. Inclisiran was associated with improved metabolic abnormalities and favorable alterations in skeletal muscle molecular and fiber-type remodeling in diabetic mice. Transcriptomic analysis identified PDK4 as a potential molecular factor associated with these skeletal muscle alterations. Inclisiran treatment was associated with reduced expression of FOXO1, PDK4, and ER stress-UPR-related markers, together with partial preservation of skeletal muscle fiber-type homeostasis. These findings provide preliminary molecular and histological evidence supporting a potential protective effect of inclisiran on diabetes-associated skeletal muscle remodeling.