An Liu

Background: Aging is characterized by a progressive decline in physiological function. Among various organs, adipose tissues play an important regulator of systemic metabolism and energy homeostasis. Age-associated alterations in adipose tissue are closely linked to organismal aging. Targeting senescent adipose tissue has therefore emerged as a potential strategy for mitigating age-related dysfunction. The purpose of this study was to develop and evaluate a selective drug delivery system for anti-aging therapy. Results: We report a targeted anti-ageing platform based on extracellular vesicles functionalized with the P3 peptide, enabling efficient delivery of dasatinib and quercetin to aged adipose tissue. This platform effectively inhibits senescence-associated secretory phenotype (SASP) in both aged adipocytes and adipose explants in vitro, concomitant with restoration of specific adipocyte function. Furthermore, systemic administration in aged mice contributes to improved physical performance and basal metabolic capacity, alongside attenuation of adipose tissue senescence. Mechanistically, these effects are probably mediated by drug-induced activation of mitophagy and the consequent reprogramming of cellular energy metabolism. Conclusion: These findings underscore the pivotal role of adipose tissue in systemic aging processes. The developed delivery platform effectively targets senescent adipose tissue, suppresses SASP, restores physiological function, and enhances organismal physical performance. This work proposes a conceptual framework linking aging and metabolism, offering a promising strategy for organ- or tissue-specific anti-aging interventions.

Chronic septic arthritis, often progressing to refractory infection due to intracellular bacterial persistence, is accompanied by dynamic macrophage immunometabolic reprogramming. Prolonged intracellular bacterial survival drives lipid metabolic remodeling in macrophages, leading to progressive accumulation of bis(monoacylglycero)phosphate (BMP), regulated by progranulin (PGRN). Mechanistically, PGRN maintains lysosomal homeostasis through direct interaction with BMP. PGRN deficiency disrupts lysosomal integrity, induces immunosuppressive polarization, and facilitates bacterial immune evasion. To address this, a dual‐targeting nanoparticle system (NPs@PGRN) targeting the “PGRN‐BMP‐lysosome” axis was developed. NPs@PGRN restores lysosomal bactericidal capacity via PGRN replenishment, significantly reduces bacterial burdens, and reprograms macrophage immunophenotypes toward antimicrobial competence. This study elucidates the central role of lipid‐immune crosstalk in chronic joint infection pathogenesis and provides a novel therapeutic strategy for it.

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.

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

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

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