关键词: Cell-free therapy Critical-sized bone defect PAA Preclinical imaging Tricalcium phosphate nanoparticles UCMSC-exosome

来  源:   DOI:10.34172/bi.2023.27510   PDF(Pubmed)

Abstract:

UNASSIGNED: This study aimed to assess the potential of poly (acrylic acid)/tricalcium phosphate nanoparticles (PAA/triCaPNPs) scaffold in terms of biocompatibility and osteoconductivity properties the in-vivo evaluation as well as to investigate the performance of PAA/triCaPNPs scaffold (with or without exosomes derived from UC-MSCs) for bone regeneration of rat critical-sized defect.
UNASSIGNED: PAA/triCaPNPs scaffold was made from acrylic acid (AA) monomer, N,N\'-methylenebisacrylamide (MBAA), sodium bicarbonate (SBC), and ammonium persulfate (APS) through freeze-drying method. For in vivo evaluation, we randomly divided 24 rats into three groups. The rat calvarial bone defects were treated as follows: (1) Control group: defects without any treatment, (2) scaffold group: defects treated with scaffold only, (3) scaffold+exo group: defects treated with scaffold enriched with exosomes (1 μg/μL, 150 μg per rat). Eight- and 12-weeks post-surgery, half of the animals were sacrificed and bone regeneration was examined through micro-computerized tomography (µ-CT), histological staining, and immunohistochemistry (IHC).
UNASSIGNED: Quantitative analysis based on µ-CT scan images at 8 and 12 weeks post-implantation clearly indicated that healing rate for defects that were filled with scaffold enriched with exosome was significantly higher than defects filled with scaffold without exosome. The H&E and Masson staining results revealed that more new bone-like form developed in the scaffold+exo group than that in control and scaffold groups. Further, IHC staining for osteocalcin and CD31 confirmed that more bone healing in the scaffold+exo group at 12 weeks could be associated with osteogenesis and angiogenesis concurrently.
UNASSIGNED: In the present study, we aimed to investigate the therapeutic potential of PAA/triCaPNPs scaffold as a carrier of human UC-MSC-derived exosome to achieve the exosome-controlled release on calvarial bone defect. The in vivo results indicated that the exosome-enriched scaffold could effectively minify the defect area and improve the bone healing in rat model, and as such it could be an option for exosome-based therapy.
摘要:

本研究旨在评估聚(丙烯酸)/磷酸三钙纳米颗粒(PAA/triCaPNPs)支架在生物相容性和骨传导性方面的潜力,体内评估以及研究PAA/triCaPNPs支架(有或没有来自UC-MSCs的外来体)用于大鼠临界尺寸缺损的骨再生的性能。
PAA/triCaPNP支架由丙烯酸(AA)单体制成,N,N'-亚甲基双丙烯酰胺(MBAA),碳酸氢钠(SBC),和过硫酸铵(APS)通过冷冻干燥法。对于体内评估,将24只大鼠随机分为3组。大鼠颅骨缺损处理如下:(1)对照组:缺损不作任何处理,(2)支架组:缺陷只用支架处理,(3)支架+外排组:用富含外泌体的支架治疗缺损(1μg/μL,每只大鼠150μg)。术后8周和12周,一半的动物被处死,骨再生通过显微计算机断层扫描(µ-CT)检查,组织学染色,免疫组织化学(IHC)。
在植入后8周和12周时基于µ-CT扫描图像的定量分析清楚地表明,填充有富含外泌体的支架的缺损的愈合率明显高于没有外泌体的支架的缺损。H&E和Masson染色结果显示,与对照组和支架组相比,在支架+外植体组中形成更多的新骨样形式。Further,骨钙蛋白和CD31的IHC染色证实,在支架+外植体组中,在12周时更多的骨愈合可能与成骨和血管生成同时相关。
在本研究中,我们的目的是研究PAA/triCaPNPs支架作为人类UC-MSC来源的外泌体的载体,以实现外泌体对颅骨缺损的控制释放的治疗潜力。体内实验结果表明,富含外泌体的支架能有效缩小大鼠模型骨缺损面积,促进骨愈合。因此,它可能是基于外泌体的治疗的一种选择。
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