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从脱细胞细胞外基质中可控递送富血小板血浆可增强骨骼肌再生。

Controlled delivery of PRP from decellularized extracellular matrix enhances skeletal muscle regeneration.

作者信息

Erfanian Saeideh, Mostafaei Farhad, Ajalloueian Fatemeh, Baharvand Hossein, Rajabi Sarah, Ashtiani Mohammad Kazemi

机构信息

Department of Tissue Engineering, Faculty of Basic Sciences and Advanced Technologies in Medicine, Royan Institute, ACECR, Tehran, Iran.

Animal Core Facility, Reproductive Biomedicine Research Center, Royan Institute for Animal Biotechnology, ACECR, Tehran, Iran.

出版信息

Sci Rep. 2025 Apr 13;15(1):12719. doi: 10.1038/s41598-025-92319-8.

DOI:10.1038/s41598-025-92319-8
PMID:40223147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11994754/
Abstract

The efficacy of platelet-rich plasma (PRP) in enhancing muscle regeneration was limited due to uncontrolled delivery. This study focuses on modification of decellularized scaffolds derived from skeletal muscle extracellular matrix (ECM) by heparin, loading with PRP, to enhance endogenous cell recruitment in muscle regeneration. Here, we showed an optimal decellularization procedure that effectively removed cells while preserving the ECM components in skeletal muscle tissue and the macroporous scaffolds showed suitable physical and mechanical properties for muscle tissue engineering. Heparinized scaffold released platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) in a sustained manner. Moreover, the scaffold increased the metabolic activity and myogenic differentiation of C2C12 cells. In addition, histological analysis revealed higher angiogenesis and more extensive migration of the host muscle cells in the volumetric muscle loss (VML) model. The heparinized scaffold facilitated the attraction and sustained release of growth factors from PRP, which in turn promoted the recruitment of the endothelial and muscle cells in the injured tissue that may have the potential to enhance the accessibility of decellularized scaffolds for off-the-shelf use and to treat muscle defects in clinical practice.

摘要

由于递送不受控制,富血小板血浆(PRP)在促进肌肉再生方面的疗效有限。本研究聚焦于用肝素修饰源自骨骼肌细胞外基质(ECM)的脱细胞支架,并负载PRP,以增强肌肉再生过程中的内源性细胞募集。在此,我们展示了一种优化的脱细胞程序,该程序能有效去除细胞,同时保留骨骼肌组织中的ECM成分,且大孔支架展现出适合肌肉组织工程的物理和力学性能。肝素化支架能持续释放血小板衍生生长因子(PDGF)、成纤维细胞生长因子(FGF)和血管内皮生长因子(VEGF)。此外,该支架增加了C2C12细胞的代谢活性和肌源性分化。另外,组织学分析显示,在容积性肌肉损失(VML)模型中,血管生成增加,宿主肌肉细胞迁移更广泛。肝素化支架促进了PRP中生长因子的吸引和持续释放,这反过来又促进了受损组织中内皮细胞和肌肉细胞的募集,这可能有潜力提高脱细胞支架的现货可用性,并在临床实践中治疗肌肉缺损。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7af/11994754/beb06e040ac4/41598_2025_92319_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7af/11994754/c09dff4099c7/41598_2025_92319_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7af/11994754/51e9188cf2c9/41598_2025_92319_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7af/11994754/53fe7610599c/41598_2025_92319_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7af/11994754/ec5bc2f8e59d/41598_2025_92319_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7af/11994754/dbe3a9e47068/41598_2025_92319_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7af/11994754/beb06e040ac4/41598_2025_92319_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7af/11994754/c09dff4099c7/41598_2025_92319_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7af/11994754/51e9188cf2c9/41598_2025_92319_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7af/11994754/53fe7610599c/41598_2025_92319_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7af/11994754/ec5bc2f8e59d/41598_2025_92319_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7af/11994754/dbe3a9e47068/41598_2025_92319_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7af/11994754/beb06e040ac4/41598_2025_92319_Fig6_HTML.jpg

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本文引用的文献

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Biomaterial-Based Regenerative Strategies for Volumetric Muscle Loss: Challenges and Solutions.基于生物材料的容积性肌肉损失再生策略:挑战与解决方案
Adv Wound Care (New Rochelle). 2025 Mar;14(3):159-175. doi: 10.1089/wound.2024.0079. Epub 2024 Jul 10.
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Delivery of adipose-derived growth factors from heparinized adipose acellular matrix accelerates wound healing.来自肝素化脂肪脱细胞基质的脂肪源性生长因子的递送可加速伤口愈合。
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Tissue engineering modalities in skeletal muscles: focus on angiogenesis and immunomodulation properties.
组织工程学在骨骼肌中的应用模式:关注血管生成和免疫调节特性。
Stem Cell Res Ther. 2023 Apr 15;14(1):90. doi: 10.1186/s13287-023-03310-x.
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Heparin-based sericin hydrogel-encapsulated basic fibroblast growth factor for in vitro and in vivo skin repair.基于肝素的丝胶蛋白水凝胶包裹碱性成纤维细胞生长因子用于体外和体内皮肤修复。
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Platelet-rich plasma-loaded bioactive chitosan@sodium alginate@gelatin shell-core fibrous hydrogels with enhanced sustained release of growth factors for diabetic foot ulcer healing.富含血小板血浆的生物活性壳聚糖@海藻酸钠@明胶核壳纤维水凝胶,具有增强的生长因子持续释放能力,用于糖尿病足溃疡愈合。
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