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血小板源性生长因子-BB延缓兔临床前模型中椎间盘退变

PDGF-BB Delays Degeneration of the Intervertebral Discs in a Rabbit Preclinical Model.

作者信息

Paglia David N, Singh Hardeep, Karukonda Teja, Drissi Hicham, Moss Isaac L

机构信息

From the UConn Health Center, Department of Orthopaedic Surgery, Farmington, CT.

出版信息

Spine (Phila Pa 1976). 2016 Apr;41(8):E449-58. doi: 10.1097/BRS.0000000000001336.

Abstract

STUDY DESIGN

Preclinical animal study.

OBJECTIVE

Determine the in vivo effects of platelet-derived growth factor BB (PDGF-BB) delivered in a thiol-modified hyaluronic acid (TMHA) hydrogel on intervertebral disk (IVD) degeneration.

SUMMARY OF BACKGROUND DATA

IVD degeneration is a worldwide health concern and remains without an effective treatment. Several in vitro studies have demonstrated the potential of PDGF-BB, a primary component of platelet-rich plasma, as a therapy for IVD degeneration. Our hypotheses were that treatment of injured IVDs with PDGF would inhibit degeneration and that administration of PDGF in a TMHA hydrogel would improve its efficacy.

METHODS

IVD degeneration was induced using the rabbit annular puncture model. Four weeks after injury, IVDs were treated with either PDGF-BB or PDGF-BB delivered within a TMHA hydrogel. The efficacy of treatment was determined using x-ray, MRI, histology, and biomechanical testing.

RESULTS

At 4 weeks after treatment, cell apoptosis and deposition of matrix containing type III collagen a1 (Col3a1) was demonstrated in both the nucleus pulposus and annulus fibrosus, while this was inhibited by PDGF. At 8 weeks after treatment, disc area and MRI indices of injured IVDs treated with PDGF were significantly higher (P < 0.05) than those treated with the TMHA alone. Similarly, degenerative scores for saline- and TMHA-treated IVDs demonstrated significantly more degeneration (P < 0.05) than PDGF-treated IVDs at 8 weeks. Biomechanical assessments found fewer indicators of degeneration in PDGF-TMHA-treated IVDs at both 4 and 8 weeks post-treatment, compared to saline-, TMHA-, and PDGF-only-treated IVDs. Both PDGF- and PDGF-TMHA-treated IVDs also demonstrated a significant increase (P < 0.05) in compressive strength to failure, compared with controls at 8 weeks post-treatment.

CONCLUSION

The results of this study suggest that PDGF-BB significantly decreases disc degeneration and when delivered in a TMHA gel scaffold, helps prevent both apoptosis and Col3 matrix production, while maintaining disc structure and biomechanical function.

LEVEL OF EVIDENCE

NA.

摘要

研究设计

临床前动物研究。

目的

确定在硫醇修饰的透明质酸(TMHA)水凝胶中递送的血小板衍生生长因子BB(PDGF-BB)对椎间盘(IVD)退变的体内影响。

背景数据总结

IVD退变是一个全球性的健康问题,目前仍缺乏有效的治疗方法。多项体外研究表明,富含血小板血浆的主要成分PDGF-BB具有治疗IVD退变的潜力。我们的假设是,用PDGF治疗受损的IVD将抑制退变,并且在TMHA水凝胶中施用PDGF将提高其疗效。

方法

使用兔椎间盘穿刺模型诱导IVD退变。损伤4周后,用PDGF-BB或在TMHA水凝胶中递送的PDGF-BB治疗IVD。使用X射线、MRI、组织学和生物力学测试来确定治疗效果。

结果

治疗4周后,在髓核和纤维环中均显示出细胞凋亡以及含III型胶原α1(Col3a1)的基质沉积,而PDGF可抑制这种情况。治疗8周后,用PDGF治疗的受损IVD的椎间盘面积和MRI指标显著高于单独用TMHA治疗的IVD(P<0.05)。同样,在8周时,用盐水和TMHA治疗的IVD的退变评分显示出比用PDGF治疗的IVD明显更多的退变(P<0.05)。生物力学评估发现,与用盐水、TMHA和仅用PDGF治疗的IVD相比,在治疗后4周和8周时,用PDGF-TMHA治疗的IVD的退变指标更少。与治疗后8周的对照组相比,用PDGF和PDGF-TMHA治疗的IVD在抗压强度至破坏方面也均有显著增加(P<0.05)。

结论

本研究结果表明,PDGF-BB可显著降低椎间盘退变,并且当在TMHA凝胶支架中递送时,有助于防止细胞凋亡和Col3基质产生,同时维持椎间盘结构和生物力学功能。

证据水平

无。

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