An in situ photocrosslinkable platelet rich plasma - Complexed hydrogel glue with growth factor controlled release ability to promote cartilage defect repair
An in situ photocrosslinkable platelet rich plasma - Complexed hydrogel glue with growth factor controlled release ability to promote cartilage defect repair
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DOI：
10.1016/j.actbio.2017.05.023
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发表时间：
2017-10-15
影响因子：
9.7
通讯作者：
Zhu, Linyong
中科院分区：
文献类型：
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作者：
Liu, Xiaolin;Yang, Yunlong;Zhu, Linyong
关节软骨损伤的修复是一项巨大的临床挑战。富血小板血浆（PRP）因其含有多种有利于创面修复的生长因子，在关节软骨损伤修复中备受关注。然而，目前PRP的给药方法存在生物固定不稳定、生长因子爆断释放等缺点，使其在关节软骨修复中的应用变得复杂，影响了其治疗效果。本研究在前人报道的光诱导亚胺交联（PIC）反应的基础上，通过添加光响应透明质酸（HA-NB），制备了一种原位光交联PRP水凝胶胶（HNPRP），该透明质酸在光照射下产生醛基，随后与氨基反应，形成自体PRP。我们的研究表明，HNPRP水凝胶胶具有细胞相容性，可以方便、快速地原位制备，形成坚固的水凝胶支架。此外，我们的研究结果表明，HNPRP水凝胶不仅实现了生长因子的控释，而且表现出较强的组织粘附能力。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水凝胶可以促进软骨细胞和骨髓干细胞（BMSCs）的增殖和迁移。兔全层软骨缺损模型的体内实验表明，HNPRP水凝胶可实现整体透明软骨再生，其治疗效果优于凝血酶活化的PRP凝胶。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水凝胶胶不仅具有生长因子的控释能力，而且具有较强的组织黏附性，可以解决目前PRP在临床应用中存在的问题。此外，HNPRP水凝胶胶能促进整体透明软骨再生，其对软骨缺损的修复效果优于凝血酶活化的PRP凝胶。本研究不仅为软骨再生提供了一种有效的修复材料，而且为PRP的应用开发了一种先进的方法。(C) 2017材料学报Elsevier Ltd.出版。版权所有。
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 SignificanceIn 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. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.