Enhancing Fracture Healing with 3D Bioprinted Hif1a-Overexpressing BMSCs Hydrogel: A Novel Approach to Accelerated Bone Repair.

IF 10 2区 医学 Q1 ENGINEERING, BIOMEDICAL Advanced Healthcare Materials Pub Date : 2024-11-24 DOI:10.1002/adhm.202402415
Jiajia Lu, Xiaojian Shi, Zhibin Zhou, Nan Lu, Guangxin Chu, Hai Jin, Lei Zhu, Aimin Chen
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Abstract

Addressing the urgent need for effective fracture treatments, this study investigates the efficacy of a 3D bioprinted biomimetic hydrogel, enriched with bone marrow mesenchymal stem cells (BMSCs) and targeted hypoxia-inducible factor 1 alpha (Hif1a) gene activation, in enhancing fracture healing. A photocross-linkable bioink, gelatin methacryloyl bone matrix anhydride (GBMA) is developed, and selected its 5% concentration for bioink formulation. Rat BMSCs are isolated and combined with GBMA to create the GBMA@BMSCs bioink. This bioink is then used in 3D bioprinting to fabricate a hydrogel for application in a rat femoral fracture model. Through transcriptome sequencing, WGCNA, and Venn analysis, the hypoxia-inducible factor Hif1a is identified as a critical gene in the fracture healing process. In vitro studies showed that Hif1a promoted BMSC proliferation, chondrogenic differentiation, and cartilage matrix stability. The in vivo application of the GBMA@BMSCs hydrogel with Hif1a overexpression significantly accelerated fracture healing, evidenced by early and enhanced cartilage callus formation. The study demonstrates that 3D bioprinting of GBMA@BMSCs hydrogel, particularly with Hif1a-enhanced BMSCs, offers a promising approach for rapid and effective fracture repair.

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用三维生物打印 Hif1a 过度表达 BMSCs 水凝胶促进骨折愈合:加速骨修复的新方法
为了满足有效治疗骨折的迫切需求,本研究探讨了一种富含骨髓间充质干细胞(BMSCs)并靶向激活缺氧诱导因子 1 alpha(Hif1a)基因的三维生物打印仿生水凝胶在促进骨折愈合方面的功效。研究人员开发了一种可光交联的生物墨水--明胶甲基丙烯酰骨基质酸酐(GBMA),并选择其 5%的浓度用于生物墨水的配制。分离出大鼠 BMSCs,并将其与 GBMA 结合,制成 GBMA@BMSCs 生物墨水。然后将这种生物墨水用于三维生物打印,制造出一种水凝胶,应用于大鼠股骨骨折模型。通过转录组测序、WGCNA 和 Venn 分析,低氧诱导因子 Hif1a 被确定为骨折愈合过程中的关键基因。体外研究表明,Hif1a能促进BMSC增殖、软骨分化和软骨基质稳定性。在体内应用过表达 Hif1a 的 GBMA@BMSCs 水凝胶可显著加速骨折愈合,早期软骨胼胝体的形成和增强就是证明。该研究表明,GBMA@BMSCs 水凝胶的三维生物打印,尤其是与 Hif1a 增强的 BMSCs 一起使用,为快速有效的骨折修复提供了一种前景广阔的方法。
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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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