Tendon–bone insertion (TBI) injuries, such as anterior cruciate ligament injury and rotator cuff injury, are the most common soft tissue injuries. In most situations, surgical tendon/ligament reconstruction is necessary for treating such injuries. However, a significant number of cases failed because healing of the enthesis occurs through scar tissue formation rather than the regeneration of transitional tissue. In recent years, the therapeutic potential of mesenchymal stem cells (MSCs) has been well documented in animal and clinical studies, such as chronic paraplegia, non-ischemic heart failure, and osteoarthritis of the knee. MSCs are multipotent stem cells, which have self-renewability and the ability to differentiate into a wide variety of cells such as chondrocytes, osteoblasts, and adipocytes. Numerous studies have suggested that MSCs could promote angiogenesis and cell proliferation, reduce inflammation, and produce a large number of bioactive molecules involved in the repair. These effects are likely mediated by the paracrine mechanisms of MSCs, particularly through the release of exosomes. Exosomes, nano-sized extracellular vesicles (EVs) with a lipid bilayer and a membrane structure, are naturally released by various cell types. They play an essential role in intercellular communication by transferring bioactive lipids, proteins, and nucleic acids, such as mRNAs and miRNAs, between cells to influence the physiological and pathological processes of recipient cells. Exosomes have been shown to facilitate tissue repair and regeneration. Herein, we discuss the prospective applications of MSC-derived exosomes in TBI injuries. We also review the roles of MSC–EVs and the underlying mechanisms of their effects on promoting tendon–bone healing. At last, we discuss the present challenges and future research directions. Graphical Abstract

Long-term chronic inflammation after Achilles tendon injury is critical for tendinopathy. Platelet-rich plasma (PRP) injection, which is a common method for treating tendinopathy, has positive effects on tendon repair. In addition, tendon-derived stem cells (TDSCs), which are stem cells located in tendons, play a major role in maintaining tissue homeostasis and postinjury repair. In this study, injectable gelatine methacryloyl (GelMA) microparticles containing PRP laden with TDSCs (PRP–TDSC–GM) were prepared by a projection-based 3D bioprinting technique. Our results showed that PRP–TDSC–GM could promote tendon differentiation in TDSCs and reduce the inflammatory response by downregulating the PI3K–AKT pathway, thus promoting the structural and functional repair of tendons in vivo. Graphical Abstract

A novel biodegradable high-strength intramedullary nail (BIN) can affect the bone marrow microenvironment and benefit osteogenesis in vitro and in vivo.

Magnetic soft catheter (MSC) robots, renowned for their remarkable flexibility and wireless controllability, are suitable for operation in constrained and dynamic in vivo environments, and they have shown application potential for in-situ bioprinting. Nonetheless, this type of in-situ bioprinting systems currently lack intraoperative intelligent defect reconstruction (DR) techniques, relying solely on preoperative imaging to guide printing, thereby introducing considerable uncertainty into the in vivo printing procedure. Here, a binocular vision-assisted MSC robot system (BV-MSCRS) is reported to perform automatic in-situ bioprinting with minimal incision. A DR algorithm based on deep learning and binocular stereo matching technology is developed to intelligently reconstruct the 3D positions and morphologies of the target defects, thereby assisting in-situ bioprinting. In accordance with the obtained 3D reconstruction information, a magnetic control strategy is designed to actuate the MSC and execute in-situ bioprinting tasks by five orthogonal electromagnets. The effectiveness of the proposed BV-MSCRS have been verified by in-vitro printing experiments on planar surfaces and in-situ bioprinting experiments on a cartilage defect of an isolated porcine femur. This study aspires to advance minimally invasive in-situ bioprinting technology toward intelligence and automation, exploring its potential in a diversity of clinical applications, such as repair of damage on cartilage, muscle, gastric wall and liver.