Injectable DAT-ALG Hydrogel Mitigates Senescence of Loaded DPMSCs and Boosts Healing of Perianal Fistulas in Crohn's Disease.

IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Biomaterials Science & Engineering Pub Date : 2025-01-13 DOI:10.1021/acsbiomaterials.4c02043
Hanxu Gao, Danjie Xing, Menglong Wu, Yilin Hu, Jiancheng He, Shun Chen, Guangze Zhang, Fangzhou Yao, Peng Ma, Wanjiang Xue
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Abstract

Perianal fistulas (PAFs) are a severe complication of Crohn's disease that significantly impact patient prognosis and quality of life. While stem-cell-based strategies have been widely applied for PAF treatment, their efficacy remains limited. Our study introduces an injectable, temperature-controlled decellularized adipose tissue-alginate hydrogel loaded with dental pulp mesenchymal stem cells (DPMSCs) for in vivo fistula treatment. The experimental group demonstrated higher healing rates compared to surgical and DPMSCs groups, as evidenced by magnetic resonance imaging, multiplex immunohistochemical, and ELISA analyses. KEGG enrichment of differential genes suggested cellular senescence involvement in cell therapy efficacy, further confirmed by β-galactosidase staining and senescence markers (p21 and p53). Collectively, our research provides a novel therapy for PAFs and illuminates underlying mechanisms.

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可注射DAT-ALG水凝胶减轻负载DPMSCs的衰老并促进克罗恩病肛周瘘的愈合。
肛周瘘(paf)是克罗恩病的严重并发症,严重影响患者的预后和生活质量。虽然基于干细胞的策略已广泛应用于PAF治疗,但其疗效仍然有限。我们的研究介绍了一种可注射的,温度控制的脱细胞脂肪组织-海藻酸盐水凝胶,装载牙髓间充质干细胞(DPMSCs)用于体内瘘管治疗。磁共振成像、多重免疫组织化学和ELISA分析证明,实验组比手术组和DPMSCs组表现出更高的治愈率。KEGG差异基因的富集提示细胞衰老参与细胞治疗效果,β-半乳糖苷酶染色和衰老标志物(p21和p53)进一步证实了这一点。总的来说,我们的研究为paf提供了一种新的治疗方法,并阐明了潜在的机制。
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来源期刊
ACS Biomaterials Science & Engineering
ACS Biomaterials Science & Engineering Materials Science-Biomaterials
CiteScore
10.30
自引率
3.40%
发文量
413
期刊介绍: ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics: Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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