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Abstract The reconstruction of a stable, nipple-shaped cartilage graft that precisely matches the natural nipple in shape and size on the contralateral side is a clinical challenge. While 3D printing technology can efficiently and accurately manufacture customized complex structures, it faces limitations due to inadequate blood supply, which hampers the stability of nipple-shaped cartilage grafts produced using this technology. To address this issue, we employed a biodegradable biomaterial, Poly(lactic-co-glycolic acid) (PLGA), loaded with Cell-Free Fat Extract (Ceffe). Ceffe has demonstrated the ability to promote angiogenesis and cell proliferation, making it an ideal bio-ink for bioprinting precise nipple-shaped cartilage grafts. We utilized the Ceffe/PLGA scaffold to create a porous structure with a precise nipple shape. This scaffold exhibited favorable porosity and pore size, ensuring stable shape maintenance and satisfactory biomechanical properties. Importantly, it could release Ceffe in a sustained manner. Our in vitro results confirmed the scaffold’s good biocompatibility and its ability to promote angiogenesis, as evidenced by supporting chondrocyte proliferation and endothelial cell migration and tube formation. Furthermore, after 8 weeks of in vivo culture, the Ceffe/PLGA scaffold seeded with chondrocytes regenerated into a cartilage support structure with a precise nipple shape. Compared to the pure PLGA group, the Ceffe/PLGA scaffold showed remarkable vascular formation, highlighting the beneficial effects of Ceffe. These findings suggest that our designed Ceffe/PLGA scaffold with a nipple shape represents a promising strategy for precise nipple-shaped cartilage regeneration, laying a foundation for subsequent nipple reconstruction.

Artificial tracheal substitutes encounter significant challenges during long-segmental tracheal defects (LSTD) reconstruction, notably early postoperative anastomotic stenosis and tracheal chondromalacia. Mitigating early anastomotic stenosis by creating a compliant sutureless substitute is pivotal. Enhancing its chondrogenic capacity is equally critical for sustained healthy tracheal cartilage regeneration. This study proposes a self-healing hydrogel for sutureless tracheal anastomosis to mitigate anastomotic stenosis, enriched with kartogenin (KGN) and transforming growth factor-β1 (TGFβ1) to bolster chondrogenic properties. Initially, two precursor solutions were prepared: 1) aldehyde-modified hyaluronic acid with sulfonation and β-cyclodextrin-CHO loaded with KGN; 2) hydrazide-grafted gelatin loaded with TGFβ1. Coextrusion of these solutions resulted in a gelated G + TGFβ1/sH-CD + KGN hydrogel, characterized by a robust covalent bonding network of acylhydrazones between hydrazide and aldehyde groups, imparting excellent self-healing properties. The G + TGFβ1/sH-CD + KGN hydrogels, showcasing favorable cytocompatibility, excellent injectability, and rapid gelation, were loaded with bone marrow stem cells. These were customized into O-shaped rings and assembled into a malleable tracheal substitute using our established ring-to-tube method. This resultant compliant substitute facilitated sutureless anastomosis of LSTD in a rabbit model, attributed to the Schiff base reaction between the hydrogel's carbonyl group and the tissue's amino group. Notably, the tracheal substitute reduced early postoperative anastomotic stenosis, maintained tracheal patency, alleviated sputum blockage, promoted reepithelization, and increased the survival rate of the experimental rabbits. The sustained release of chondrocytokines resulted in excellent tracheal cartilage regeneration. Employing chondrocytokines-loaded hydrogels with self-healing properties represents a significant advancement in sutureless tracheal anastomosis and tracheal cartilage regeneration, holding promising potential in inhibiting early postoperative anastomotic stenosis and tracheal chondromalacia when treating LSTD.

Recurrent glioblastoma (rGBM) is a highly aggressive form of brain cancer that poses a significant challenge for treatment in neuro-oncology, and the survival status of patients after relapse usually means rapid deterioration, thus becoming the leading cause of death among patients. In recent years, immunotherapy has emerged as a promising strategy for the treatment of recurrent glioblastoma by stimulating the body’s immune system to recognize and attack cancer cells, which could be used in combination with other treatments such as surgery, radiation, and chemotherapy to improve outcomes for patients with recurrent glioblastoma. This therapy combines several key methods such as the use of monoclonal antibodies, chimeric antigen receptor T cell (CAR-T) therapy, checkpoint inhibitors, oncolytic viral therapy cancer vaccines, and combination strategies. In this review, we mainly document the latest immunotherapies for the treatment of glioblastoma and especially focus on rGBM.

Bone defects caused by various factors may cause morphological and functional disorders that can seriously affect patient’s quality of life. Autologous bone grafting is morbid, involves numerous complications, and provides limited volume at donor site. Hence, tissue-engineered bone is a better alternative for repair of bone defects and for promoting a patient’s functional recovery. Besides good biocompatibility, scaffolding materials represented by hydroxyapatite (HA) composites in tissue-engineered bone also have strong ability to guide bone regeneration. The development of manufacturing technology and advances in material science have made HA composite scaffolding more closely related to the composition and mechanical properties of natural bone. The surface morphology and pore diameter of the scaffold material are more important for cell proliferation, differentiation, and nutrient exchange. The degradation rate of the composite scaffold should match the rate of osteogenesis, and the loading of cells/cytokine is beneficial to promote the formation of new bone. In conclusion, there is no doubt that a breakthrough has been made in composition, mechanical properties, and degradation of HA composites. Biomimetic tissue-engineered bone based on vascularization and innervation show a promising future.

MiRNAs and macrophages play important roles in renal fibrosis. The exosomes secreted by bone marrow mesenchymal stem cells (BM-MSCs) can alleviate renal fibrosis. What is not clear, however, is whether a type of miRNAs in the BM-MSCs exosomes can alleviate renal fibrosis by modulating macrophage polarization. First, we take a high-throughput sequencing of miRNAs in exosomes of BM-MSCs from chronic kidney disease (CKD) and normal people. Then we used the UUO mouse model and injected exosomes into the tail vein. The macrophages were stimulated with lipopolysaccharide (LPS). MSC-Exo or exosomes from BMMSCs transfected with miR-93-5p inhibitor (Inhi-Exo) were added to the culture medium. The macrophages were transfected with miR-93-5p inhibitor or miR-93-5p mimic alone. The expression of miR-93-5p in exosomes of CKD patients was significantly decreased compared with normal people and in the LPS-stimulated macrophages and UUO mice kidneys. After stimulation with LPS, the macrophages polarized toward M1 subtype. MSC-Exo or miR-93-5p mimic promoted macrophages from M1 to M2 subtype. Inhi-Exo or miR-93-5p inhibitor blocked the differentiation from M1 to M2 subtype. Significant fibrotic changes occurred in the kidneys of UUO mice, and M1 macrophages were significantly increased. After injecting exosomes into the tail vein of UUO mice, the degree of renal fibrosis was alleviated, the expression of miR-93-5p in the kidney was significantly increased, and the renal macrophages differentiated from M1 to M2 subtype. These results demonstrated that miR-93-5p in the exosomes derived from BM-MSCs can improve renal fibrosis by inducing macrophage differentiation from M1 to M2 subtype. [ABSTRACT FROM AUTHOR]