Increased therapeutic factors and retention of IONP-NVs substantially enhance therapeutic potential for cardiac repair.

Due to the safety issues and poor engraftment of mesenchymal stem cell (MSC) implantation, MSC-derived exosomes have been spotlighted as an alternative therapy for spinal cord injury (SCI). However, insufficient productivity of exosomes limits their therapeutic potential for clinical application. Moreover, low targeting ability of unmodified exosomes is a critical obstacle for their further applications as a therapeutic agent. In the present study, we fabricated macrophage membrane-fused exosome-mimetic nanovesicles (MF-NVs) from macrophage membrane-fused umbilical cord blood-derived MSCs (MF-MSCs) and confirmed their therapeutic potential in a clinically relevant mouse SCI model (controlled mechanical compression injury model). MF-NVs contained larger quantity of ischemic region-targeting molecules compared to normal MSC-derived nanovesicles (N-NVs). The targeting molecules in MF-NVs, which were derived from macrophage membranes, increased the accumulation of MF-NVs in the injured spinal cord after the in vivo systemic injection. Increased accumulation of MF-NVs attenuated apoptosis and inflammation, prevented axonal loss, enhanced blood vessel formation, decreased fibrosis, and consequently, improved spinal cord function. Synthetically, we developed targeting efficiency-potentiated exosome-mimetic nanovesicles and present their possibility of clinical application for SCI.

Regulating stem cell microenvironment is one of the essential elements in stem cell culture. Recently, carbon nanotube (CNT) has come into the spotlight as a biomaterial that retains unique properties. Based on its high chemical stability, elasticity, mechanical strength, and electrical conductivity, CNT shows great potential as an application for biomedical substrate. Also, properties of CNT could be further regulated by appropriate chemical modifications of CNT. Recent studies reported that modulating the cellular microenvironment through the use of CNT and chemically modified CNT as cell culture substrates can affect proliferation and differentiation of various types of stem cells. This review summarizes the unique biological effects of CNT on stem cells.

The rapid recruitment of osteoblasts in bone defects is an essential prerequisite for efficient bone repair. Conventionally, osteoblast recruitment to bone defects and subsequent bone repair has been achieved using growth factors. Here, we present a methodology that can guide the recruitment of osteoblasts to bone defects with topographically defined implants (TIs) for efficient in vivo bone repair. We compared circular TIs that had microgrooves in parallel or radial arrangements with non-patterned implants for osteoblast migration and in vivo bone formation. In vitro, the microgrooves in the TIs enhanced both the migration and proliferation of osteoblasts. Especially, the microgrooves with radial arrangement demonstrated a much higher efficiency of osteoblast recruitment to the implants than did the other types of implants, which may be due to the efficient guidance of cell migration toward the cell-free area of the implants. The expression of the intracellular signaling molecules responsible for the cell migration was also up-regulated in osteoblasts on the microgrooved TIs. In vivo, the TI with radially defined topography demonstrated much greater bone repair in mouse calvarial defect models than in the other types of implants. Taken together, these results indicate that implants with physical guidance can enhance tissue repair by rapid cell recruitment.

The modulation of inflammatory responses plays an important role in the pathobiology of cardiac failure. In a natural healing process, the ingestion of apoptotic cells and their apoptotic bodies by macrophages in a focal lesion result in resolution of inflammation and regeneration. However, therapeutic strategies to enhance this natural healing process using apoptotic cell‐derived biomaterials have not yet been established. In this study, apoptotic bodies‐mimetic nanovesicles derived from apoptotic fibroblasts (ApoNVs) conjugated with dextran and ischemic cardiac homing peptide (CHP) (ApoNV‐DCs) for ischemia‐reperfusion (IR)‐injured heart treatment are developed. Intravenously injected ApoNV‐DCs actively targeted the ischemic myocardium via conjugation with CHP, and are selectively phagocytosed by macrophages in an infarcted myocardium via conjugation with dextran. ApoNV‐DCs polarized macrophages from the M1 to M2 phenotype, resulting in the attenuation of inflammation. Four weeks after injection, ApoNV‐DCs attenuated cardiac remodeling, preserved blood vessels, and prevented cardiac function exacerbation in IR‐injured hearts. Taken together, the findings may open a new avenue for immunomodulation using targeted delivery of anti‐inflammatory nanovesicles that can be universally applied for various inflammatory diseases.