Organoid and organoid extracellular vesicles for osteoporotic fractures therapy: Current status and future perspectives

Abstract Osteoporosis is a systemic and degenerative disease characterized by low bone mass and fragile microarchitecture, which predispose patients to fragility fractures, also known as osteoporotic fractures (OPF). OPF have become a major social problem that threaten the health of the elderly. Over the past decade, organoids and organoids extracellular vesicles (OEVs) play a significant role in OPF repair. Organoids have been widely used for fractures treatment. Moreover, EVs are promising nanocarriers due to their cell‐free system, stable drug loading capacity, nanometer size, and good biocompatibility. Importanly, compared with traditional EVs, OEVs have more quantity, better physiological effects, and better therapeutic effects. Therefore, the development of organoid and OEVs in the treatment of OPF is of great significance. Here, we summarize the current status and future perspectives of organoids and OEVs, which will provide innovative solutions to OPF repair

Engineered mammalian and bacterial extracellular vesicles as promising nanocarriers for targeted therapy

Extracellular vesicles (EVs), which are nanocarriers with phospholipid bilayer structures released by most cells, play a key role in regulating physiological and pathological processes. EVs have been investigated due to their loading capacity, low toxicity, immunogenicity, and biofunctions. Although EVs have shown good potential as therapeutic vehicles, natural EVs have a poor targeting ability, which substantially reduces the therapeutic effect. Through the addition of a targeting unit into the membrane surface of EVs or inside EVs by engineering technology, the therapeutic agent can accumulate in specific cells and tissues. Here, we focus on mammalian EVs (MEVs) and bacterial EVs (BEVs), which are the two most common types of EVs in the biomedical field. In this review, we describe engineered MEVs and BEVs as promising nanocarriers for targeted therapy and summarize the biogenesis, isolation, and characterization of MEVs and BEVs. We then describe engineering techniques for enhancement of the targeting ability of EVs. Moreover, we focus on the applications of engineered MEVs and BEVs in targeted therapy, including the treatment of cancer and brain and bone disease. We believe that this review will help improve the understanding of engineered MEVs and BEVs, thereby promoting their application and clinical translation

Construction of Local Drug Delivery System on Titanium-Based Implants to Improve Osseointegration

Titanium and its alloys are the most widely applied orthopedic and dental implant materials due to their high biocompatibility, superior corrosion resistance, and outstanding mechanical properties. However, the lack of superior osseointegration remains the main obstacle to successful implantation. Previous traditional surface modification methods of titanium-based implants cannot fully meet the clinical needs of osseointegration. The construction of local drug delivery systems (e.g., antimicrobial drug delivery systems, anti-bone resorption drug delivery systems, etc.) on titanium-based implants has been proved to be an effective strategy to improve osseointegration. Meanwhile, these drug delivery systems can also be combined with traditional surface modification methods, such as anodic oxidation, acid etching, surface coating technology, etc., to achieve desirable and enhanced osseointegration. In this paper, we review the research progress of different local drug delivery systems using titanium-based implants and provide a theoretical basis for further research on drug delivery systems to promote bone–implant integration in the future

Bone Regeneration Using MMP-Cleavable Peptides-Based Hydrogels

Accumulating evidence has suggested the significant potential of chemically modified hydrogels in bone regeneration. Despite the progress of bioactive hydrogels with different materials, structures and loading cargoes, the desires from clinical applications have not been fully validated. Multiple biological behaviors are orchestrated precisely during the bone regeneration process, including bone marrow mesenchymal stem cells (BMSCs) recruitment, osteogenic differentiation, matrix calcification and well-organized remodeling. Since matrix metalloproteinases play critical roles in such bone metabolism processes as BMSC commitment, osteoblast survival, osteoclast activation matrix calcification and microstructure remodeling, matrix metalloproteinase (MMP) cleavable peptides-based hydrogels could respond to various MMP levels and, thus, accelerate bone regeneration. In this review, we focused on the MMP-cleavable peptides, polymers, functional modification and crosslinked reactions. Applications, perspectives and limitations of MMP-cleavable peptides-based hydrogels for bone regeneration were then discussed

Smart Hydrogels for Bone Reconstruction via Modulating the Microenvironment

Rapid and effective repair of injured or diseased bone defects remains a major challenge due to shortages of implants. Smart hydrogels that respond to internal and external stimuli to achieve therapeutic actions in a spatially and temporally controlled manner have recently attracted much attention for bone therapy and regeneration. These hydrogels can be modified by introducing responsive moieties or embedding nanoparticles to increase their capacity for bone repair. Under specific stimuli, smart hydrogels can achieve variable, programmable, and controllable changes on demand to modulate the microenvironment for promoting bone healing. In this review, we highlight the advantages of smart hydrogels and summarize their materials, gelation methods, and properties. Then, we overview the recent advances in developing hydrogels that respond to biochemical signals, electromagnetic energy, and physical stimuli, including single, dual, and multiple types of stimuli, to enable physiological and pathological bone repair by modulating the microenvironment. Then, we discuss the current challenges and future perspectives regarding the clinical translation of smart hydrogels

AI-enabled organoids: Construction, analysis, and application

Organoids, miniature and simplified in vitro model systems that mimic the structure and function of organs, have attracted considerable interest due to their promising applications in disease modeling, drug screening, personalized medicine, and tissue engineering. Despite the substantial success in cultivating physiologically relevant organoids, challenges remain concerning the complexities of their assembly and the difficulties associated with data analysis. The advent of AI-Enabled Organoids, which interfaces with artificial intelligence (AI), holds the potential to revolutionize the field by offering novel insights and methodologies that can expedite the development and clinical application of organoids. This review succinctly delineates the fundamental concepts and mechanisms underlying AI-Enabled Organoids, summarizing the prospective applications on rapid screening of construction strategies, cost-effective extraction of multiscale image features, streamlined analysis of multi-omics data, and precise preclinical evaluation and application. We also explore the challenges and limitations of interfacing organoids with AI, and discuss the future direction of the field. Taken together, the AI-Enabled Organoids hold significant promise for advancing our understanding of organ development and disease progression, ultimately laying the groundwork for clinical application