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具有空间嵌入式生长因子的生物活性支架促进兔慢性肩袖撕裂模型的骨腱界面愈合。

Bioactive Scaffold With Spatially Embedded Growth Factors Promotes Bone-to-Tendon Interface Healing of Chronic Rotator Cuff Tear in Rabbit Model.

机构信息

Department of Orthopaedic Surgery, The First People's Hospital of Huzhou, Huzhou, Zhejiang Province, China.

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

出版信息

Am J Sports Med. 2023 Jul;51(9):2431-2442. doi: 10.1177/03635465231180289. Epub 2023 Jun 22.

DOI:10.1177/03635465231180289
PMID:37345646
Abstract

BACKGROUND

Functional restoration of the bone-to-tendon interface (BTI) after rotator cuff repair is a challenge. Therefore, numerous biocompatible biomaterials for promoting BTI healing have been investigated.

PURPOSE

To determine the efficacy of scaffolds with spatiotemporal delivery of growth factors (GFs) to accelerate BTI healing after rotator cuff repair.

STUDY DESIGN

Controlled laboratory study.

METHODS

An advanced 3-dimensional printing technique was used to fabricate bioactive scaffolds with spatiotemporal delivery of multiple GFs targeting the tendon, fibrocartilage, and bone regions. In total, 50 rabbits were used: 2 nonoperated controls and 48 rabbits with induced chronic rotator cuff tears (RCTs). The animals with RCTs were divided into 3 groups: (A) saline injection, (B) scaffold without GF, and (C) scaffold with GF. To induce chronic models, RCTs were left unrepaired for 6 weeks; then, surgical repairs with or without bioactive scaffolds were performed. For groups B and C, each scaffold was implanted between the bony footprint and the supraspinatus tendon. Four weeks after repair, quantitative real-time polymerase chain reaction and immunofluorescence analyses were performed to evaluate early signs of regenerative healing. Histological, biomechanical, and micro-computed tomography analyses were performed 12 weeks after repair.

RESULTS

Group C had the highest mRNA expression of collagen type I alpha 1, collagen type III alpha 1, and aggrecan. Immunofluorescence analysis showed the formation of an aggrecan/collagen II fibrocartilaginous matrix at the BTI when repaired with scaffold with GFs. Histologic analysis revealed greater collagen fiber continuity, denser collagen fibers, and a more mature tendon-to-bone junction in GF-embedded scaffolds than those in the other groups. Group C demonstrated the highest load-to-failure ratio, and modulus mapping showed that the distribution of the micromechanical properties of the BTI repaired with GF-embedded scaffolds was comparable with that of the native BTI. Micro-computed tomography analysis identified the highest bone mineral density and bone volume/total volume ratio in group C.

CONCLUSION

Bioactive scaffolds with spatially embedded GFs have significant potential to promote the BTI healing of chronic RCTs in a rabbit model.

CLINICAL RELEVANCE

The scaffolds with spatiotemporal delivery of GF may serve as an off-the-shelf biomaterial graft to promote the healing of RCTs.

摘要

背景

肩袖修复后骨-腱界面(BTI)的功能恢复是一个挑战。因此,已经研究了许多用于促进 BTI 愈合的生物相容性生物材料。

目的

确定时空递呈生长因子(GFs)支架加速肩袖修复后 BTI 愈合的功效。

研究设计

对照实验室研究。

方法

使用先进的 3 维打印技术制造具有时空递呈针对腱、纤维软骨和骨区域的多种 GFs 的生物活性支架。总共使用了 50 只兔子:2 只非手术对照和 48 只诱导的慢性肩袖撕裂(RCT)兔子。RCT 兔子分为 3 组:(A)生理盐水注射,(B)无 GF 支架,和(C)GF 支架。为了诱导慢性模型,RCT 未修复 6 周;然后,进行带有或不带有生物活性支架的修复手术。对于组 B 和 C,每个支架都植入在骨附着点和冈上肌腱之间。修复后 4 周,进行定量实时聚合酶链反应和免疫荧光分析以评估再生愈合的早期迹象。修复后 12 周进行组织学、生物力学和微计算机断层扫描分析。

结果

组 C 的胶原 I 型 alpha 1、胶原 III 型 alpha 1 和聚集蛋白聚糖的 mRNA 表达最高。免疫荧光分析显示,在修复带有 GFs 的支架时,在 BTI 处形成了聚集蛋白聚糖/胶原 II 纤维软骨基质。组织学分析显示,在含有 GFs 的支架中,胶原纤维连续性更好,胶原纤维更密集,腱骨交界处更成熟。组 C 表现出最高的失效负荷比,模数映射显示,含有 GFs 的支架修复的 BTI 的微力学性能分布与天然 BTI 相当。微计算机断层扫描分析显示组 C 的骨矿物质密度和骨体积/总体积比最高。

结论

具有空间嵌入 GFs 的生物活性支架具有显著的潜力,可促进兔模型中慢性 RCT 的 BTI 愈合。

临床相关性

时空递呈 GF 的支架可作为一种即用型生物材料移植物,促进 RCT 的愈合。

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