Osteogenesis of Human iPSC-Derived MSCs by PLLA/SF Nanofiber Scaffolds Loaded with Extracellular Matrix

IF 3.1 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Tissue Engineering and Regenerative Medicine Pub Date : 2023-02-06 DOI:10.1155/2023/5280613

Junming Zhang, Lingbin Che, Yunliang Wu, Lei Zhou, Li Liu, Yuanhang Yue, D. Song, X. Lou

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引用次数: 1

Abstract

Bone defects that arise from trauma, skeletal diseases, or tumor resections have become the commonest and most thorny problems in orthopedic clinics. Recently, biocomposite materials used as artificial bone repair materials have provided a promising approach for bone regeneration. In this study, poly (l-lactide acid) (PLLA) and silk fibroin (SF) were used to fabricate nanofiber scaffolds by electrospinning technology. In order to simulate a biomimetic osteoblast microenvironment, decellularized extracellular matrix from osteoblasts was loaded into the biocomposite scaffolds (O-ECM/PLLA/SF). It was found that the O-ECM/PLLA/SF scaffolds were nontoxic for L929 cells and had good cytocompatibility. Their effects on mesenchymal stem cells derived from human-induced pluripotent stem cell (iPSC-MSC) behavior were investigated. As a result, the scaffolds with the addition of O-ECM showed enhanced alizarin red S (ARS) activity. In addition, higher expression of osteogenic gene markers such as runt-related transcription factor 2 (Runx2), collagen type I (Col-1), and osteocalcin (OCN) as well as upregulated expression of osteogenic marker protein osteopontin (OPN) and Col-1 further substantiated the applicability of O-ECM/PLLA/SF scaffolds for osteogenesis. Furthermore, the in vivo study also indicated maximal new bone formation in the skull defect model of Sprague Dawley (SD) rats treated with the O-ECM/PLLA/SF carried by human iPSC-MSCs. Hence, this study suggests that O-ECM/PLLA/SF scaffolds have a potential application in bone tissue engineering.

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负载细胞外基质的PLLA/SF纳米纤维支架对人iPSC衍生MSCs的成骨作用

由创伤、骨骼疾病或肿瘤切除引起的骨缺损已成为骨科诊所中最常见和最棘手的问题。近年来，生物复合材料作为人工骨修复材料为骨再生提供了一种很有前途的途径。本研究以聚乳酸（PLLA）和丝素蛋白（SF）为原料，采用静电纺丝技术制备了纳米纤维支架。为了模拟仿生成骨细胞微环境，将成骨细胞的脱细胞细胞外基质负载到生物复合支架（O-ECM/PLLA/SF）中。结果表明，O-ECM/PLLA/SF支架对L929细胞无毒，具有良好的细胞相容性。研究了它们对来源于人诱导多能干细胞（iPSC-MSC）行为的间充质干细胞的影响。结果，添加O-ECM的支架显示出增强的茜素红S（ARS）活性。此外，成骨基因标记物如runt相关转录因子2（Runx2）、I型胶原（Col-1）和骨钙素（OCN）的高表达，以及成骨标记蛋白骨桥蛋白（OPN）和Col-1的上调表达，进一步证实了O-ECM/PLLA/SF支架在成骨中的适用性。此外，体内研究还表明，在用人iPSC MSC携带的O-ECM/PLLA/SF处理的Sprague-Dawley（SD）大鼠颅骨缺损模型中，新骨形成最大。因此，本研究表明O-ECM/PLLA/SF支架在骨组织工程中具有潜在的应用前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Tissue Engineering and Regenerative Medicine 生物-工程：生物医学

CiteScore

7.50

自引率

3.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Journal of Tissue Engineering and Regenerative Medicine publishes rapidly and rigorously peer-reviewed research papers, reviews, clinical case reports, perspectives, and short communications on topics relevant to the development of therapeutic approaches which combine stem or progenitor cells, biomaterials and scaffolds, growth factors and other bioactive agents, and their respective constructs. All papers should deal with research that has a direct or potential impact on the development of novel clinical approaches for the regeneration or repair of tissues and organs. The journal is multidisciplinary, covering the combination of the principles of life sciences and engineering in efforts to advance medicine and clinical strategies. The journal focuses on the use of cells, materials, and biochemical/mechanical factors in the development of biological functional substitutes that restore, maintain, or improve tissue or organ function. The journal publishes research on any tissue or organ and covers all key aspects of the field, including the development of new biomaterials and processing of scaffolds; the use of different types of cells (mainly stem and progenitor cells) and their culture in specific bioreactors; studies in relevant animal models; and clinical trials in human patients performed under strict regulatory and ethical frameworks. Manuscripts describing the use of advanced methods for the characterization of engineered tissues are also of special interest to the journal readership.