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三维打印的重组人甲状旁腺激素浸泡的纳米纤维片在慢性肩袖撕裂兔模型中加速腱骨愈合。

Three-dimensionally printed recombinant human parathyroid hormone-soaked nanofiber sheet accelerates tendon-to-bone healing in a rabbit model of chronic rotator cuff tear.

作者信息

Han Jian, Rhee Sung Min, Kim Young Won, Park Suk Hee, Oh Joo Han

机构信息

Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Republic of Korea.

Department of Orthopaedic Surgery, KyungHee University Medical Center, Seoul, Republic of Korea.

出版信息

J Shoulder Elbow Surg. 2022 Aug;31(8):1628-1639. doi: 10.1016/j.jse.2022.02.013. Epub 2022 Mar 23.

Abstract

BACKGROUND

Recombinant human parathyroid hormone (rhPTH) promotes tendon-to-bone healing in humans and animals with rotator cuff tear (RCT). However, problems regarding repeated systemic rhPTH injections in humans exist. This study was conducted to evaluate the effect of topical rhPTH administration using 3-dimensionally (3D) printed nanofiber sheets on tendon-to-bone healing in a rabbit RCT model compared to that of direct topical rhPTH administration.

METHODS

Eighty rabbits were randomly assigned to 5 groups (n = 16 each). To create the chronic RCT model, we induced complete supraspinatus tendon tears in both shoulders and left them untreated for 6 weeks. All transected tendons were repaired in a transosseous manner with saline injection in group A, hyaluronic acid (HA) injection in group B, 3D-printed nanofiber sheet fixation in group C, rhPTH and HA injection in group D, and 3D-printed rhPTH- and HA-soaked nanofiber sheet fixation in group E. Genetic (messenger RNA expression evaluation) and histologic evaluations (hematoxylin and eosin and Masson trichrome staining) were performed in half of the rabbits at 4 weeks postrepair. Genetic, histologic, and biomechanical evaluations (mode of tear and load to failure) were performed in the remaining rabbits at 12 weeks.

RESULTS

For genetic evaluation, group E showed a higher collagen type I alpha 1 expression level than did the other groups (P = .008) at 4 weeks. However, its expression level was downregulated, and there was no difference at 12 weeks. For histologic evaluation, group E showed greater collagen fiber continuity, denser collagen fibers, and more mature tendon-to-bone junction than did the other groups (P = .001, P = .001, and P = .003, respectively) at 12 weeks. For biomechanical evaluation, group E showed a higher load-to-failure rate than did the other groups (P < .001) at 12 weeks.

CONCLUSION

Three-dimensionally printed rhPTH-soaked nanofiber sheet fixation can promote tendon-to-bone healing of chronic RCT.

摘要

背景

重组人甲状旁腺激素(rhPTH)可促进患有肩袖撕裂(RCT)的人类和动物的肌腱-骨愈合。然而,在人类中重复进行全身性rhPTH注射存在问题。本研究旨在评估使用三维(3D)打印纳米纤维片局部给予rhPTH与直接局部给予rhPTH相比,对兔RCT模型中肌腱-骨愈合的影响。

方法

80只兔子被随机分为5组(每组n = 16)。为建立慢性RCT模型,我们在双侧肩部诱导冈上肌腱完全撕裂,并使其未经治疗6周。A组经皮注射生理盐水、B组注射透明质酸(HA)、C组采用3D打印纳米纤维片固定、D组注射rhPTH和HA、E组采用3D打印的rhPTH和HA浸泡的纳米纤维片固定,所有横断肌腱均采用经骨缝合法修复。修复后4周,对一半兔子进行基因(信使核糖核酸表达评估)和组织学评估(苏木精-伊红染色和Masson三色染色)。在其余兔子修复后12周进行基因、组织学和生物力学评估(撕裂模式和破坏载荷)。

结果

基因评估方面,4周时E组I型胶原α1表达水平高于其他组(P = 0.008)。然而,其表达水平在12周时下调,且无差异。组织学评估方面,12周时E组胶原纤维连续性更好、胶原纤维更致密、肌腱-骨结合更成熟,均优于其他组(分别为P = 0.001、P = 0.001和P = 0.003)。生物力学评估方面,12周时E组破坏载荷率高于其他组(P < 0.001)。

结论

3D打印的rhPTH浸泡纳米纤维片固定可促进慢性RCT的肌腱-骨愈合。

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