With the markedly increased diagnosis and incidence of cancer in the population, tumor bone metastasis has become a frequent event in tumor patients. Healthy bone integrity is maintained by a delicate balance between bone formation and bone resorption. Unfortunately, many tumors, such as prostate and breast, often metastasize to the bone, and the alterations to the bone homeostasis can particularly favor tumor homing and consequent osteolytic or osteoblastic lesions. Receptor activator of NF-κB ligand (RANKL), its receptor RANK, and osteoprotegerin (OPG) are involved in the regulation of the activation, differentiation, and survival of osteoclasts, which play critical roles in bone metastasis formation. High rates of osteoclastic bone resorption significantly increase fracture risk, cause severe bone pain, and contribute to homing tumor cells in bone and bone marrow. Consequently, suppression of the RANK/RANKL/OPG system and osteoclastic activity can not only ameliorate bone resorption but may also prevent tumor bone metastases. This review summarizes the important role of the RANK/RANKL/OPG system and osteoclasts in bone homeostasis and its effect on tumor bone metastasis and discusses therapeutic strategies based on RANKL inhibition.

Osteoarthritis (OA) poses a significant burden for countless individuals, inflicting relentless pain and impairing their quality of life. Although traditional treatments for OA focus on pain management and surgical interventions, they often fall short of addressing the underlying cause of the disease. Fortunately, emerging biomaterial-based scaffolds offer hope for OA therapy, providing immense promise for cartilage regeneration in OA. These innovative scaffolds are ingeniously designed to provide support and mimic the intricate structure of the natural extracellular matrix, thus stimulating the regeneration of damaged cartilage. In this comprehensive review, we summarize and discuss current landscape of biomaterial-based scaffolds for cartilage regeneration in OA. Furthermore, we delve into the diverse range of biomaterials employed in their construction and explore the cutting-edge techniques utilized in their fabrication. By examining both preclinical and clinical studies, we aim to illuminate the remarkable versatility and untapped potential of biomaterial-based scaffolds in the context of OA. By thoroughly examining the current state of research and clinical studies, this review provides valuable insights that bridge the gap between scientific knowledge and practical application. This knowledge is crucial for clinicians and researchers who strive to develop innovative treatments that go beyond symptom management and directly target the underlying cause of OA. Through the comprehensive analysis and multidisciplinary approach, the review paves the way for the translation of scientific knowledge into practical applications, ultimately improving the lives of individuals suffering from OA and shaping the future of orthopedic medicine.

Tissue engineering holds great potential for tissue repair and rejuvenation. Plant-derived exosome-like nanoparticles (ELNs) have recently emerged as a promising avenue in tissue engineering. However, there is an urgent need to understand how plant ELNs can be therapeutically applied in clinical disease management, especially for tissue regeneration. In this review, we comprehensively examine the properties, characteristics, and isolation techniques of plant ELNs. We also discuss their impact on the immune system, compatibility with the human body, and their role in tissue regeneration. To ensure the suitability of plant ELNs for tissue engineering, we explore various engineering and modification strategies. Additionally, we provide insights into the progress of commercialization and industrial perspectives on plant ELNs. This review aims to highlight the potential of plant ELNs in regenerative medicine by exploring the current research landscape and key findings.

Diabetic wounds (DW) constitute a substantial burden on global healthcare owing to their widespread occurrence as a complication of diabetes. Angiogenesis, a crucial process, plays a pivotal role in tissue recovery by supplying essential oxygen and nutrients to the injury site. Unfortunately, in diabetes mellitus, various factors disrupt angiogenesis, hindering wound healing. While biomaterials designed to enhance angiogenesis hold promise for the treatment of DWs, there is an urgent need for more in-depth investigations to fully unlock their potential in clinical management. In this review, we explore the intricate mechanisms of angiogenesis that are crucial for DW recovery. We introduce a rational design for angiogenesis-enhancing drug delivery systems (DDS) and provide a comprehensive summary and discussion of diverse biomaterials that enhance angiogenesis for facilitating DW healing. Lastly, we address emerging challenges and prospects in angiogenesis-enhancing DDS for facilitating DW healing, aiming to offer a comprehensive understanding of this critical healthcare issue and potential solutions.

Exosomes, remarkable extracellular vesicles, have emerged as an advanced frontier in intercellular communication. This remarkable capacity positions them as promising contenders in drug delivery systems (DDSs) for osteoarthritis (OA) therapy, capitalizing on their inherent biocompatibility, stability, and minimal immunogenicity. In this comprehensive review, we summarize the emerging developments surrounding exosome-based DDSs for OA therapy. Focusing on exosome origins, we meticulously explore the diverse sources contributing to their production, including invaluable stem cells, immune cells, and an array of other cell types. In addition, we unravel the underlying mechanisms of action that govern these exosome-borne therapeutics, illuminating the intricate interplay between exosomes and recipient cells. In summary, this review highlights the present challenges that permeate exosome-based DDSs for OA therapy. Through an in-depth exploration of the intricacies within this emerging field, this review aims to shed light on the future direction of exosome-based DDSs in OA. It serves as a bridge for fostering collaboration and collective efforts in reshaping the treatment landscape of OA.

Osteoarthritis (OA) is a chronic degenerative disease afflicting millions globally. Despite the development of numerous pharmacological treatments for OA, a substantial unmet need for effective therapies persists. The RANK/RANKL signaling pathway has emerged as a promising therapeutic target for OA, owing to its pivotal role in regulating osteoclast differentiation and activity. In this comprehensive review, we aim to elucidate the relevant mechanisms of OA mediated by RANK/RANKL signaling, including bone remodeling, inflammation, cartilage degradation, osteophyte formation, and pain sensitization. Furthermore, we discuss and summarize the cutting-edge strategies targeting RANK/RANKL signaling for OA therapy, encompassing approaches such as gene-based interventions and biomaterials-aided pharmacotherapy. In addition, we highlight the prevailing challenges associated with pharmacological OA treatments and explore potential future directions, approached through a clinical-translational lens.