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Point-of-Care Procedure for Enhancement of Meniscal Healing in a Goat Model Utilizing Infrapatellar Fat Pad-Derived Stromal Vascular Fraction Cells Seeded in Photocrosslinkable Hydrogel.
The American Journal of Sports Medicine ( IF 4.8 ) Pub Date : 2019-10-23 , DOI: 10.1177/0363546519880468
Benjamin B Rothrauff 1 , Hiroshi Sasaki 1 , Shinsuke Kihara 1 , Kalon J Overholt 1 , Riccardo Gottardi 1 , Hang Lin 1 , Freddie H Fu 1 , Rocky S Tuan 1 , Peter G Alexander 1
Affiliation  

Background:

Large radial tears of the meniscus involving the avascular region can compromise meniscal function and result in poor healing and subsequent osteochondral degeneration. Augmentation of surgical repairs with adipose-derived stromal vascular fraction (SVF), which contains mesenchymal stromal cells, may improve meniscal healing and preserve function (ie, chondroprotection).

Purposes:

(1) To develop a goat model of a radial meniscal tear with resulting osteoarthritis and (2) to explore the efficacy of a 1-step procedure utilizing infrapatellar fat pad–derived SVF cells seeded in a photocrosslinkable hydrogel to enhance meniscal healing and mitigate osteochondral degeneration.

Study Design:

Controlled laboratory study.

Methods:

A full-thickness radial tear spanning 90% of the medial meniscal width was made at the junction of the anterior and middle bodies of the goat stifle joint. Tears received 1 of 3 interventions (n = 4 per group): untreated, repair, or repair augmented with photocrosslinkable methacrylated gelatin hydrogel containing 2.0 × 106 SVF cells/mL and 2.0 µg/mL of transforming growth factor β3. The contralateral (left) joint served as a healthy control. At 6 months, meniscal healing and joint health were evaluated by magnetic resonance imaging (MRI) and assessed by histological and macroscopic scoring. The Whole-Organ Magnetic Resonance Imaging Score and the presence of a residual tear, as evaluated with T2 MRI sequences, were determined by a single blinded orthopaedic surgeon.

Results:

When compared with tears left untreated or repaired with suture alone, augmented repairs demonstrated increased tissue formation in the meniscal tear site, as seen on MRI and macroscopically. Likewise, the neotissue of augmented repairs possessed a histological appearance more similar, although still inferior, to healthy meniscus. Osteochondral degeneration in the medial compartment, as evaluated by the Whole-Organ Magnetic Resonance Imaging Score and Inoue (macroscopic) scale, revealed increased degeneration in the untreated and repair groups, which was mitigated in the augmented repair group. Histological evaluation with a modified Mankin score showed a similar trend. In all measures of osteochondral degeneration, the augmented repair group did not differ significantly from the uninjured control.

Conclusion:

A radial tear spanning 90% of the medial meniscal width in a goat stifle joint showed poor healing potential and resulted in osteochondral degeneration by 6 months, even if suture repair was performed. Augmentation of the repair with a photocrosslinkable hydrogel containing transforming growth factor β3 and SVF cells, isolated intraoperatively by rapid enzymatic digestion, improved meniscal healing and mitigated osteoarthritic changes.

Clinical Relevance:

Repair augmentation with an SVF cell–seeded hydrogel may support successful repair of meniscal tears previously considered irreparable.



中文翻译:

利用接种在可光交联水凝胶中的In下脂肪垫衍生基质血管分数细胞,在山羊模型中增强半月板愈合的护理点程序。

背景:

涉及无血管区域的半月板大的径向撕裂会损害半月板功能并导致愈合不良和随后的骨软骨变性。包含间质基质细胞的脂肪来源的基质血管部分(SVF)可以增强外科手术的修复,可改善半月板愈合并保持功能(即软骨保护)。

用途:

(1)建立伴有骨关节炎的radial骨半月板撕裂的山羊模型,(2)探索使用植入在可光交联水凝胶中的pad下脂肪垫衍生的SVF细胞来增强半月板愈合和减轻骨软骨炎的1步法的功效退化。

学习规划:

对照实验室研究。

方法:

在山羊窒息关节的前体和中体交界处制作了一个全厚度的径向撕裂,其撕裂度为半月板内侧宽度的90%。眼泪接受了3种干预措施中的1种(每组n = 4):未经治疗,修复或通过含有2.0×10 6 SVF细胞/ mL和2.0 µg / mL转化生长因子β3的可光交联的甲基丙烯酸明胶水凝胶进行增强。对侧(左)关节作为健康对照。在6个月时,通过磁共振成像(MRI)评估半月板愈合和关节健康,并通过组织学和宏观评分评估。T2 MRI序列评估的全器官磁共振成像评分和残余泪液的存在是由一个单盲的骨科医生确定的。

结果:

与未经治疗或仅用缝合线修复的眼泪相比,增强的修复表现出在半月板眼泪部位的组织形成增加,如在MRI和宏观上所见。同样,增强修复的新组织的组织学外观与健康的半月板相比,尽管仍然不如其更差。通过全器官磁共振成像评分和井上(宏观)量表评估,内侧腔内的软骨软骨变性显示未治疗组和修复组的变性增加,而增强修复组则得到缓解。修改后的Mankin评分的组织学评估显示出相似的趋势。在所有骨软骨变性的测量中,增强修复组与未受伤对照组无显着差异。

结论:

即使进行缝合修复,山羊a骨关节中半月板内侧宽度的90%的tear骨撕裂显示出较弱的愈合潜力,并在6个月后导致骨软骨变性。使用含有转化生长因子β3和SVF细胞的可光交联水凝胶增强修复作用,可在术中通过快速酶消化将其分离出来,改善半月板愈合并减轻骨关节炎的改变。

临床相关性:

用SVF细胞接种的水凝胶进行的修复增强可能支持成功修复以前认为无法修复的半月板撕裂。

更新日期:2019-10-23
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