After peripheral nerve injury, nerve guidance conduits (NGCs) offer an effective alternative to autologous nerve grafting for repairing nerve defects. However, without a well-defined topological structure, peripheral nerve regeneration often results in disorganized growth. Because the regeneration site is subject to bodily movement, the conduits must possess sufficient mechanical integrity to function within this dynamic environment. We prepared double-network hydrogel films from polyvinyl alcohol (PVA) and gelatin for nerve regeneration applications. Using freeze-thaw crystallization, the Hofmeister effect, borate bonding, and incorporating poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), along with continuous optimization of the formulation, the hydrogel achieved excellent mechanical properties. With repeated mechanical training, the hydrogel surface developed a fibrous-like topological structure and could also carry and gradually release nerve growth factor (NGF). The hydrogel could be shaped by cutting and origami folding, and was then firmly attached to the nerve defect via chitosan stitching adhesives, providing a foundation for nerve regeneration. The conduit exhibited a degradation rate closely matching the nerve regeneration process and excellent biocompatibility, while also promoting the oriented growth and differentiation of PC12 cells. In vivo evaluation in a rat sciatic nerve defect model demonstrated that the conduit suppressed inflammation, activated calcium signaling and PPAR pathways in the early regenerative phase, and promoted axon regeneration, remyelination, and functional recovery.
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Open Access
Research Article
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Open Access
Original Article
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Lower grade gliomas (LGGs), classified as World Health Organization (WHO) grade Ⅱ and grade Ⅲ gliomas, comprise a heterogeneous group with a median survival time ranging from 4–13 years. Accurate prediction of the survival times of LGGs remains a major challenge in clinical practice.
We reviewed the expression data of 865 LGG patients from 5 transcriptomics cohorts. The comparative profile of immune genes was analyzed for signature identification and validation. In-house RNAseq and microarray data from the Chinese Glioma Genome Atlas (CGGA) dataset were used as training and internal validation cohorts, respectively. The samples from The Cancer Genome Atlas (TCGA) and GSE16011 cohorts were used as external validation cohorts, and the real-time PCR of frozen LGG tissue samples (n = 36) were used for clinical validation.
A total of 2,214 immune genes were subjected to pairwise comparison to generate 2,449,791 immune-related gene pairs (IGPs). A total of 402 IGPs were identified with prognostic values for LGGs. The HOXA9-related and CRH-related scores facilitated identification of patients with different prognoses. An immune signature based on 10 IGPs was constructed to stratify patients into low and high risk groups, exhibiting different clinical outcomes. A nomogram, combining immune signature, 1p/19q status, and tumor grade, was able to predict the overall survival (OS) with c-indices of 0.85, 0.80, 0.80, 0.79, and 0.75 in the training, internal validation, external validation, and tissue sample cohorts, respectively.
This study was the first to report a comparative profiling of immune genes in large LGG cohorts. A promising individualized immune signature was developed to estimate the survival time for LGG patients.
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