Over the last decade, adipose‐derived stem cells (ADSCs) have attracted increasing attention in the field of regenerative medicine. ADSCs appear to be the most advantageous cell type for regenerative therapies owing to their easy accessibility, multipotency, and active paracrine activity. This review highlights current challenges in translating ADSC‐based therapies into clinical settings and discusses novel strategies to overcome the limitations of ADSCs. To further establish ADSC‐based therapies as an emerging platform for regenerative medicine, this review also provides an update on the advancements in this field, including fat grafting, wound healing, bone regeneration, skeletal muscle repair, tendon reconstruction, cartilage regeneration, cardiac repair, and nerve regeneration. ADSC‐based therapies are expected to be more tissue‐specific and increasingly important in regenerative medicine.

Poor wound healing after diabetes mellitus remains a challenging problem, and its pathophysiological mechanisms have not yet been fully elucidated. Persistent bleeding, disturbed regulation of inflammation, blocked cell proliferation, susceptible infection and impaired tissue remodeling are the main features of diabetic wound healing. Conventional wound dressings, including gauze, films and bandages, have a limited function. They generally act as physical barriers and absorbers of exudates, which fail to meet the requirements of the whol diabetic wound healing process. Wounds in diabetic patients typically heal slowly and are susceptible to infection due to hyperglycemia within the wound bed. Once bacterial cells develop into biofilms, diabetic wounds will exhibit robust drug resistance. Recently, the application of stimuli-responsive hydrogels, also known as “smart hydrogels”, for diabetic wound healing has attracted particular attention. The basic feature of this system is its capacities to change mechanical properties, swelling ability, hydrophilicity, permeability of biologically active molecules, etc., in response to various stimuli, including temperature, potential of hydrogen (pH), protease and other biological factors. Smart hydrogels can improve therapeutic efficacy and limit total toxicity according to the characteristics of diabetic wounds. In this review, we summarized the mechanism and application of stimuli-responsive hydrogels for diabetic wound healing. It is hoped that this work will provide some inspiration and suggestions for research in this field.

In this study, we investigated the mechanisms by which puerarin alleviates osteoclast-related loss of bone mass in ovariectomy (OVX)-induced osteoporosis model mice. Puerarin-treated OVX mice exhibited higher bone density, fewer tartrate-resistant acid phosphatase (TRAcP)-positive osteoclasts, and levels of lower reactive oxygen species (ROS) within bone tissues than vehicle-treated OVX mice. Puerarin suppressed in vitro osteoclast differentiation, hydroxyapatite resorption activity, and expression of osteoclastogenesis-related genes, such as NFATc1, MMP9, CTSK, Acp5 and c-Fos, in RANKL-induced bone marrow macrophages (BMMs) and RAW264.7 cells. It also reduced intracellular ROS levels by suppressing expression of TRAF6 and NADPH oxidase 1 (NOX1) and increasing expression of antioxidant enzymes such as heme oxygenase-1 (HO-1). Puerarin inhibited TRAF6/ROS-dependent activation of the MAPK and NF-κB signaling pathways in RANKL-induced RAW264.7 cells, and these effects were partially reversed by HO-1 silencing or TRAF6 overexpression. These findings suggest puerarin alleviates loss of bone mass in the OVX-model mice by suppressing osteoclastogenesis via inhibition of the TRAF6/ROS-dependent MAPK/NF-κB signaling pathway.

Since the proposal of Paul Ehrlich’s magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for skeletal diseases more challenging than other tissues. Bone-targeted therapy has been considered a promising therapeutic approach for handling such drawbacks. With the deepening understanding of bone biology, improvements in some established bone-targeted drugs and novel therapeutic targets for drugs and deliveries have emerged on the horizon. In this review, we provide a panoramic summary of recent advances in therapeutic strategies based on bone targeting. We highlight targeting strategies based on bone structure and remodeling biology. For bone-targeted therapeutic agents, in addition to improvements of the classic denosumab, romosozumab, and PTH1R ligands, potential regulation of the remodeling process targeting other key membrane expressions, cellular crosstalk, and gene expression, of all bone cells has been exploited. For bone-targeted drug delivery, different delivery strategies targeting bone matrix, bone marrow, and specific bone cells are summarized with a comparison between different targeting ligands. Ultimately, this review will summarize recent advances in the clinical translation of bone-targeted therapies and provide a perspective on the challenges for the application of bone-targeted therapy in the clinic and future trends in this area.

As a highly dynamic tissue, bone is continuously rebuilt throughout life. Both bone formation by osteoblasts and bone resorption by osteoclasts constitute bone reconstruction homeostasis. The equilibrium of bone homeostasis is governed by many complicated signaling pathways that weave together to form an intricate network. These pathways coordinate the meticulous processes of bone formation and resorption, ensuring the structural integrity and dynamic vitality of the skeletal system. Dysregulation of the bone homeostatic regulatory signaling network contributes to the development and progression of many skeletal diseases. Significantly, imbalanced bone homeostasis further disrupts the signaling network and triggers a cascade reaction that exacerbates disease progression and engenders a deleterious cycle. Here, we summarize the influence of signaling pathways on bone homeostasis, elucidating the interplay and crosstalk among them. Additionally, we review the mechanisms underpinning bone homeostatic imbalances across diverse disease landscapes, highlighting current and prospective therapeutic targets and clinical drugs. We hope that this review will contribute to a holistic understanding of the signaling pathways and molecular mechanisms sustaining bone homeostasis, which are promising to contribute to further research on bone homeostasis and shed light on the development of targeted drugs.