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通过聚己内酯支架上的聚(乳酸-乙醇酸)纳米颗粒同步长期递送生长激素和胰岛素样生长因子1以增强骨软骨再生。

Synchronized long-term delivery of growth hormone and insulin-like growth factor 1 through poly (lactic-co-glycolic acid) nanoparticles on polycaprolactone scaffolds for enhanced osteochondral regeneration.

作者信息

Li Dong, Zheng Suyang, Wei Peiran, Xu Yan, Hu Wenhao, Ma Shengshan, Tang Cheng, Wang Liming

机构信息

Department of Orthopedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China; Department of Trauma Center, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People's Republic of China.

Department of Orthopedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China; Department of Orthopedics, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.

出版信息

Int J Biol Macromol. 2024 Dec;282(Pt 4):136781. doi: 10.1016/j.ijbiomac.2024.136781. Epub 2024 Oct 24.

DOI:10.1016/j.ijbiomac.2024.136781
PMID:39454927
Abstract

The regeneration of osteochondral defects is challenging due to the complex structure of the osteochondral unit. This study aimed to develop a biomimetic scaffold by loading growth hormone (GH) and insulin-like growth factor-1 (IGF-1) into poly (lactic-co-glycolic acid) (PLGA) nanoparticles and incorporating them into polycaprolactone (PCL) scaffolds to promote synchronized osteochondral regeneration. The nanoparticles were successfully immobilized onto PCL scaffolds pre-modified with polydopamine (PDA) to enhance cell adhesion and proliferation. The scaffolds exhibited a sustained release of GH and IGF-1 over 30 days. In vitro studies using rabbit adipose-derived stem cells (ADSCs) showed that the GH/IGF-1 nanoparticle-loaded scaffolds (PCL/PDA/M-PLGA) significantly promoted cell proliferation, chondrogenic differentiation, and osteogenic differentiation compared to control PCL/PDA scaffolds. In vivo experiments using a rabbit osteochondral defect model revealed that the PCL/PDA/M-PLGA scaffolds facilitated superior osteochondral regeneration, evidenced by increased subchondral bone formation and cartilage matrix deposition. Overall, this study demonstrates the potential of GH/IGF-1 nanoparticle-loaded PCL scaffolds for synchronized osteochondral regeneration and provides a promising strategy for treating osteochondral defects.

摘要

由于骨软骨单元的复杂结构,骨软骨缺损的再生具有挑战性。本研究旨在通过将生长激素(GH)和胰岛素样生长因子-1(IGF-1)负载到聚乳酸-羟基乙酸共聚物(PLGA)纳米颗粒中,并将其掺入聚己内酯(PCL)支架中,以促进同步骨软骨再生,从而开发一种仿生支架。纳米颗粒成功固定在经聚多巴胺(PDA)预修饰的PCL支架上,以增强细胞粘附和增殖。支架在30天内持续释放GH和IGF-1。使用兔脂肪来源干细胞(ADSCs)的体外研究表明,与对照PCL/PDA支架相比,负载GH/IGF-1纳米颗粒的支架(PCL/PDA/M-PLGA)显著促进细胞增殖、软骨生成分化和成骨分化。使用兔骨软骨缺损模型的体内实验表明,PCL/PDA/M-PLGA支架促进了更好的骨软骨再生,这通过软骨下骨形成增加和软骨基质沉积得到证明。总体而言,本研究证明了负载GH/IGF-1纳米颗粒的PCL支架在同步骨软骨再生方面的潜力,并为治疗骨软骨缺损提供了一种有前景的策略。

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