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三维生物打印支架袖带联合间充质干细胞促进前交叉韧带重建中使用软组织肌腱移植物的腱骨愈合

Three-Dimensional Bio-Printed Scaffold Sleeves With Mesenchymal Stem Cells for Enhancement of Tendon-to-Bone Healing in Anterior Cruciate Ligament Reconstruction Using Soft-Tissue Tendon Graft.

机构信息

Department of Orthopaedic Surgery, Soonchunhyang University School of Medicine, Bucheon Hospital, Bucheon, Republic of Korea.

Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.

出版信息

Arthroscopy. 2018 Jan;34(1):166-179. doi: 10.1016/j.arthro.2017.04.016. Epub 2017 Jul 6.

Abstract

PURPOSE

To investigate the efficacy of the insertion of 3-dimensional (3D) bio-printed scaffold sleeves seeded with mesenchymal stem cells (MSCs) to enhance osteointegration between the tendon and tunnel bone in anterior cruciate ligament (ACL) reconstruction in a rabbit model.

METHODS

Scaffold sleeves were fabricated by 3D bio-printing. Before ACL reconstruction, MSCs were seeded into the scaffold sleeves. ACL reconstruction with hamstring tendon was performed on both legs of 15 adult rabbits (aged 12 weeks). We implanted 15 bone tunnels with scaffold sleeves with MSCs and implanted another 15 bone tunnels with scaffold sleeves without MSCs before passing the graft. The specimens were harvested at 4, 8, and 12 weeks. H&E staining, immunohistochemical staining of type II collagen, and micro-computed tomography of the tunnel cross-sectional area were evaluated. Histologic assessment was conducted with a histologic scoring system.

RESULTS

In the histologic assessment, a smooth bone-to-tendon transition through broad fibrocartilage formation was identified in the treatment group, and the interface zone showed abundant type II collagen production on immunohistochemical staining. Bone-tendon healing histologic scores were significantly higher in the treatment group than in the control group at all time points. Micro-computed tomography at 12 weeks showed smaller tibial (control, 9.4 ± 0.9 mm; treatment, 5.8 ± 2.9 mm; P = .044) and femoral (control, 9.6 ± 2.9 mm; treatment, 6.0 ± 1.0 mm; P = .03) bone-tunnel areas in the treated group than in the control group.

CONCLUSIONS

The 3D bio-printed scaffold sleeve with MSCs exhibited excellent results in osteointegration enhancement between the tendon and tunnel bone in ACL reconstruction in a rabbit model.

CLINICAL RELEVANCE

If secure biological healing between the tendon graft and tunnel bone can be induced in the early postoperative period, earlier, more successful rehabilitation may be facilitated. Three-dimensional bio-printed scaffold sleeves with MSCs have the potential to accelerate bone-tendon healing in ACL reconstruction.

摘要

目的

研究在兔前交叉韧带(ACL)重建模型中,植入三维(3D)生物打印支架套并接种间充质干细胞(MSCs)以增强肌腱与隧道骨之间骨整合的效果。

方法

通过 3D 生物打印制造支架套。在 ACL 重建之前,将 MSCs 接种到支架套中。在 15 只成年兔(12 周龄)的双侧膝关节进行跟腱 ACL 重建。我们在植入移植物前在 15 个骨隧道中植入了带有 MSC 的支架套,在另外 15 个骨隧道中植入了没有 MSC 的支架套。在 4、8 和 12 周时采集标本。评估 H&E 染色、II 型胶原免疫组织化学染色和隧道横截面积的微计算机断层扫描。采用组织学评分系统进行组织学评估。

结果

在组织学评估中,在治疗组中观察到通过广泛纤维软骨形成的平滑的骨-腱过渡,并且在免疫组织化学染色中界面区显示出丰富的 II 型胶原产生。在所有时间点,治疗组的骨-腱愈合组织学评分均明显高于对照组。12 周时的微计算机断层扫描显示,治疗组胫骨(对照组 9.4 ± 0.9mm;治疗组 5.8 ± 2.9mm;P =.044)和股骨(对照组 9.6 ± 2.9mm;治疗组 6.0 ± 1.0mm;P =.03)骨隧道面积均小于对照组。

结论

在兔 ACL 重建模型中,MSCs 增强的 3D 生物打印支架套在增强肌腱与隧道骨之间的骨整合方面表现出优异的效果。

临床相关性

如果能在术后早期诱导肌腱移植物和隧道骨之间的安全生物学愈合,可能会促进更早、更成功的康复。MSCs 增强的 3D 生物打印支架套有可能加速 ACL 重建中的骨-腱愈合。

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