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原位光交联富血小板血浆-复合水凝胶胶具有生长因子控释能力,可促进软骨缺损修复。

An in situ photocrosslinkable platelet rich plasma - Complexed hydrogel glue with growth factor controlled release ability to promote cartilage defect repair.

机构信息

Institute of Microsurgery on Extremities, Institute of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People' Hospital, 600 # Yishan Road, Shanghai 200233, China.

Key Laboratory for Advanced Materials, Institute of Fine Chemicals, East China University of Science and Technology, 130# Meilong Road, Shanghai 200237, China.

出版信息

Acta Biomater. 2017 Oct 15;62:179-187. doi: 10.1016/j.actbio.2017.05.023. Epub 2017 May 10.

DOI:10.1016/j.actbio.2017.05.023
PMID:28501713
Abstract

UNLABELLED

The repair of articular cartilage injury is a great clinical challenge. Platelet-rich plasma (PRP) has attracted much attention for the repair of articular cartilage injury, because it contains various growth factors that are beneficial for wound repair. However, current administration methods of PRP have many shortcomings, such as unstable biological fixation and burst release of growth factors, all of which complicate its application in the repair of articular cartilage and compromise its therapeutic efficacy. In this study, based on our previously reported photoinduced imine crosslinking (PIC) reaction, we developed an in situ photocrosslinkable PRP hydrogel glue (HNPRP) through adding a photoresponsive hyaluronic acid (HA-NB) which could generate aldehyde groups upon light irradiation and subsequently react with amino groups, into autologous PRP. Our study showed that HNPRP hydrogel glue was cytocompatible and could be conveniently and rapidly prepared in situ, forming a robust hydrogel scaffold. In addition, our results demonstrated that HNPRP hydrogel not only achieved controlled release of growth factors, but also showed strong tissue adhesive ability. Therefore, HNPRP hydrogel was quite suitable for cartilage defect regeneration. Our further in vitro experiment showed that HNPRP hydrogel could promote the proliferation and migration of chondrocytes and bone marrow stem cells (BMSCs). In vivo testing using a rabbit full-thickness cartilage defect model demonstrated that HNPRP hydrogel could achieve integrative hyaline cartilage regeneration and its therapeutic efficacy was better than thrombin activated PRP gel.

STATEMENT OF SIGNIFICANCE

In this study, we have developed a photocrosslinkable platelet rich plasma (PRP) - complexed hydrogel glue (HNPRP) for cartilage regeneration. The in situ formed HNPRP hydrogel glue showed not only the controlled release ability of growth factors, but also strong tissue adhesiveness, which could resolve the current problems in clinical application of PRP. Furthermore, HNPRP hydrogel glue could promote integrative hyaline cartilage regeneration, and its reparative efficacy for cartilage defect was better than thrombin activated PRP gel. This study provided not only an effective repair material for cartilage regeneration, but also developed an advanced method for PRP application.

摘要

未加标签

关节软骨损伤的修复是一个巨大的临床挑战。富血小板血浆(PRP)因其含有多种有利于伤口修复的生长因子而引起了人们对关节软骨损伤修复的关注。然而,目前 PRP 的给药方式存在许多缺点,例如生物固定不稳定和生长因子的爆发释放,所有这些都使 PRP 在关节软骨修复中的应用复杂化,并降低了其治疗效果。在这项研究中,基于我们之前报道的光诱导亚胺交联(PIC)反应,我们通过添加一种光响应透明质酸(HA-NB),该透明质酸在光照下会产生醛基,然后与氨基反应,将其加入到自体 PRP 中,开发了一种原位光交联 PRP 水凝胶胶(HNPRP)。我们的研究表明,HNPRP 水凝胶胶具有细胞相容性,并且可以方便、快速地原位制备,形成坚固的水凝胶支架。此外,我们的结果表明,HNPRP 水凝胶不仅实现了生长因子的控制释放,而且表现出很强的组织黏附能力。因此,HNPRP 水凝胶非常适合软骨缺损的再生。我们进一步的体外实验表明,HNPRP 水凝胶能促进软骨细胞和骨髓基质干细胞(BMSCs)的增殖和迁移。在使用兔全层软骨缺损模型的体内试验中,证明 HNPRP 水凝胶能实现整合性透明软骨再生,其治疗效果优于凝血酶激活的 PRP 凝胶。

意义声明

在这项研究中,我们开发了一种用于软骨再生的光交联富血小板血浆(PRP)复合水凝胶胶(HNPRP)。原位形成的 HNPRP 水凝胶胶不仅表现出生长因子的控制释放能力,而且具有很强的组织黏附性,这可以解决 PRP 在临床应用中存在的问题。此外,HNPRP 水凝胶胶能促进整合性透明软骨再生,对软骨缺损的修复效果优于凝血酶激活的 PRP 凝胶。本研究不仅为软骨再生提供了有效的修复材料,而且为 PRP 的应用开发了一种先进的方法。

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