Xiaoxia Song

Endometriosis is referred to as a “benign cancer,” severely impacting women’s reproductive health. However, the pathogenesis of endometriosis remains unclear. This study aims to investigate the potential roles of lipid metabolism-related genes (LMRGs) and immune infiltration in the diagnosis and pathogenesis of endometriosis. Four microarray datasets (GSE6364, GSE51981, GSE153740, and GSE232713) with eutopic endometrium samples of the midsecretory phase were downloaded from the Gene Expression Omnibus database. Seven hundred forty LMRGs were obtained from the Reactome database. The GSE6364 and GSE51981 datasets were merged and differentially expressed genes (DEGs) were identified between endometriosis patients and normal controls. Lipid metabolism-related DEGs were detected by intersecting the DEGs and LMRGs. Functional enrichment analysis, protein–protein interaction analysis, and receiver operating characteristic analysis of lipid metabolism-related DEGs were performed. Additionally, immune cell infiltration was compared between endometriosis patients and normal controls, and associations with lipid metabolism-related DEGs were assessed. Fifty-eight lipid metabolism-related DEGs were identified in endometriosis patients compared with normal controls, which enriched in glycerolipids, fatty acyls, sphingolipids, glycerophospholipids, and sterol lipids metabolism, especially steroid hormone metabolism and arachidonic acid metabolism. Additionally, 11 core genes were identified, with HMGCR and CYP27A1 validated as potential markers for diagnosing endometriosis and assessing its severity, respectively. Immune infiltration analysis revealed that fibroblasts and B lineage cells were predominantly abnormal in the endometrium of the midsecretory phase in endometriosis. Correlation analysis suggested that core genes were closely related to immune cells. In conclusion, HMGCR and CYP27A1 were identified as potential markers for endometriosis and its severity, respectively. Fibroblasts and B lineage cells may significantly contribute to the reduced endometrial receptivity observed in endometriosis. These findings provide new insights into the diagnostic and pathogenic roles of LMRGs in endometriosis and highlight their implications for infertility and pregnancy complications related to endometriosis.

Glioblastoma multiforme (GBM) is a highly invasive and fatal brain tumor with a grim prognosis, where current treatment modalities, including postoperative radiotherapy and temozolomide chemotherapy, yield a median survival of only 15 months. The challenges of tumor heterogeneity, drug resistance, and the blood-brain barrier necessitate innovative therapeutic approaches. This study introduces a strategy employing biomimetic magnetic nanorobots encapsulated with hybrid membranes derived from platelets and M1 macrophages to enhance blood-brain barrier penetration and target GBM. The nanorobots encapsulate a polypyrrole/Fe₃O₄ nanocomplex (PPy@F) for photothermal therapy (PTT) and promote the Fenton reaction of Fe₃O₄ to generate chemodynamic therapy (CDT). Additionally, temozolomide and PD-L1 antibody (SNTSESF) act as chemotherapy drug and immune checkpoint inhibitor, respectively. The biomimetic design leverages the functional properties of cell membranes to improve the blood residence time and tumor targeting. The integration of PTT and CDT aims to transform "cold" tumors into "hot" tumors, thereby enhancing immunotherapeutic efficacy. This multifaceted approach, PTT, CT, CDT, and immune checkpoint blockade therapy, offers a promising strategy for the treatment of GBM.

Cell delivery using magnetic microswimmers is a promising tool for targeted therapy. However, it remains challenging to rapidly and uniformly manufacture cell-loaded microswimmers that can be assembled into cell-supporting structures at diseased sites. Here, rapid and uniform manufacturable 2D magnetic achiral microswimmers with pores were fabricated to deliver bone marrow mesenchymal stem cells (BMSCs) to regenerate articular-damaged cartilage. Under actuation with magnetic fields, the BMSC-loaded microswimmers take advantage of the achiral structure to exhibit rolling or swimming motions to travel on smooth and rough surfaces, up inclined planes, or in the bulk fluid. Cell viability, proliferation, and differentiation tests performed days after cell seeding verified the microswimmers' biocompatibility. Long-distance targeting and in situ assemblies into 3D cell-supporting structures with BMSC-loaded microswimmers were demonstrated using a knee model and U-shaped wells. Overall, combining the advantages of preparing an achiral 2D structured microswimmer with magnetically driven motility results in a platform for cell transport and constructing 3D cell cultures that can improve cell delivery at lesion sites for biomedical applications.

Biohybrid micro/nanorobots have demonstrated improved therapeutic outcomes for targeting and treating diseases in preclinical trials. However, in vivo applications remain challenging due to a lack of sufficient targeting. Based on evidence that immune cells play a role in the immune modulation in the tumor microenvironment, we developed M1 macrophage membrane-coated magnetic photothermal nanocomplexes (MPN) for photoacoustic (PA) imaging-guided tumor therapy. The MPN were able to inherit the protein from the original macrophage cells and exert a targeted immunosuppression role. Integrating black phosphorus quantum dots and DOX also greatly enhanced reactive oxygen species generation and chemo-phototherapy efficacy. The results suggest that the MPN can be employed as an excellent tumor immunotargeting nanorobotic platform for modulating the tumor microenvironment under PA imaging and magnetic guidance and, thus, exert synergistic therapeutic efficacies.

Magnetically actuated microrobots showed increasing potential in various fields, especially in the biomedical area, such as invasive surgery, targeted cargo delivery, and treatment. However, it remains a challenge to incorporate biocompatible natural polymers that are favorable for practical biomedical applications. In this work, bilayer magnetic microrobots with an achiral planar design were fabricated using a biocompatible natural polymer and Fe₃O₄ nanoparticles through the photolithography by applying the layer-by-layer method. The microrobots consisted of a magnetic bottom layer and a photo-crosslinked chitosan top layer. The SEM results showed that the microrobot processed the L-shaped planar structure with the average width, length, and thickness of 99.18 ± 5.11 μm, 189.56 ± 11.37 μm, and 23.56 ± 4.08 μm, respectively. Moreover, microrobots actuated using a three-dimensional (3D) Helmholtz coil system was characterized and reached up to an average maximum velocity of 325.30 μm/s and a step-out frequency of 14 Hz. Furthermore, the microrobots exhibited excellent cell biocompatibility towards L929 cells in the CCK-8 assay. Therefore, the development of bi-layered chitosan-based microrobots offers a general solution for using magnetic microrobots in biomedical applications by providing an easy-to-fabricate, highly mobile microrobotic platform with the incorporation of biocompatible natural polymers for enhanced biocompatibility.

The small size of robotic microswimmers makes them suitable for performing biomedical tasks in tiny, enclosed spaces. Considering the effects of potentially long-term retention of microswimmers in biological tissues and the environment, the degradability of microswimmers has become one of the pressing issues in this field. While degradable hydrogel was successfully used to prepare microswimmers in previous reports, most hydrogel microswimmers could only be fabricated using two-photon polymerization (TPP) due to their 3D structures, resulting in costly robotic microswimmers solution. This limits the potential of hydrogel microswimmers to be used in applications where a large number of microswimmers are needed. Here, we proposed a new type of preparation method for degradable hydrogel achiral crescent microswimmers using a custom-built stop-flow lithography (SFL) setup. The degradability of the hydrogel crescent microswimmers was quantitatively analyzed, and the degradation rate in sodium hydroxide solution (NaOH) of different concentrations was investigated. Cytotoxicity assays showed the hydrogel crescent microswimmers had good biocompatibility. The hydrogel crescent microswimmers were magnetically actuated using a 3D Helmholtz coil system and were able to obtain a swimming efficiency on par with previously reported microswimmers. The results herein demonstrated the potential for the degradable hydrogel achiral microswimmers to become a candidate for microscale applications.

This review focuses on magnetically driven bio-hybrid micro actuators, categorized by major biological component, for environmental and biomedical applications.

Nanoscale manipulation of material surfaces can create extraordinary properties, holding great potential for modulating the implant–bio interface for enhanced performance. In this study, a green, simple and biocompatible nanosurfacing approach based on weak alkalinity-activated solid-state dewetting (AAD) was for the first time developed to nano-manipulate the Ti6Al4V surface by atomic self-rearrangement. AAD treatment generated quasi-periodic titanium oxide nanopimples with high surface energy. The nanopimple-like nanostructures enhanced the osteogenic activity of osteoblasts, facilitated M2 polarization of macrophages, and modulated the cross-talk between osteoblasts and macrophages, which collectively led to significant strengthening of in vivo bone–implant interfacial bonding. In addition, the titanium oxide nanopimples strongly adhered to the Ti alloy, showing resistance to tribocorrosion damage. The results suggest strong nano–bio interfacial effects, which was not seen for the control Ti alloy processed through traditional thermal oxidation. Compared to other nanostructuring strategies, the AAD technique shows great potential to integrate high-performance, functionality, practicality and scalability for surface modification of medical implants.