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纤维蛋白注射入猪椎间盘的生物学和生物力学效应。

Biological and biomechanical effects of fibrin injection into porcine intervertebral discs.

机构信息

Department of Orthopaedic Surgery, University of California, San Francisco, CA, USA.

出版信息

Spine (Phila Pa 1976). 2011 Aug 15;36(18):E1201-9. doi: 10.1097/BRS.0b013e31820566b2.

DOI:10.1097/BRS.0b013e31820566b2
PMID:21325992
Abstract

STUDY DESIGN

Surgically denucleated porcine intervertebral discs (IVD) were injected with BIOSTAT BIOLOGX Fibrin Sealant (FS), and the in vivo effects were assessed over time by histological, biochemical, and mechanical criteria.

OBJECTIVE

The objectives were to test whether the intradiscal injection of FS stimulates disc healing.

SUMMARY OF BACKGROUND DATA

Disc avascularity prevents the deposition of a provisional fibrin scaffold that typically facilitates soft tissue repair. Poor disc wound healing leads to disc damage accumulation and chronic inflammation characterized by overproduction of proinflammatory cytokines and proteolytic enzymes.

METHODS

Four lumbar IVDs from each of 31 Yucatan minipigs were randomized to untreated controls; degenerative injury (nucleotomy); and nucleotomy plus FS injection. Animals were killed at 1, 2, 3, 6, and 12 weeks postsurgery. IVDs were harvested to quantify (1) architecture using morphological and histological grading; (2) proteoglycan composition using DMMB assay; (3) cytokine content using ELISA; and (4) mechanical properties using quantitative pressure/volume testing.

RESULTS

There was progressive invasion of annular tissue into the nucleus of nucleotomy discs and concomitant reduction in proteoglycan content. By contrast, FS supplementation inhibited nuclear fibrosis and facilitated proteoglycan content recovery over time. FS discs synthesized significantly less TNF-α than degenerate discs (66% vs. 226%, P < 0.05) and had upregulation of IL-4 (310% vs. 166%) and TGF-β (400% vs. 117%) at 2 to 3 weeks posttreatment. At the third week postsurgery, the denucleated discs were less stiff than controls (pressure modulus 779.9 psi vs. 2754.8 psi; P < 0.05) and failed at lower pressures (250.5 psi vs. 492.5 psi; P < 0.05). The stiffness and leakage pressure of the FS-treated discs recovered to control values after 6 and 12 weeks, respectively.

CONCLUSION

FS facilitated structural, compositional, and mechanical repair of the surgically damaged IVD. These FS-derived benefits are likely due to its conductive scaffold properties and metabolically active constituents such as thrombin, factor XIII, and aprotinin acetate.

摘要

研究设计

对手术去核的猪椎间盘中枢进行 BIOSTAT BIOLOGX 纤维蛋白密封剂(FS)注射,并通过组织学、生物化学和力学标准评估其体内的随时间推移的效果。

目的

本研究旨在测试 FS 椎间盘内注射是否能刺激椎间盘愈合。

背景资料概要

椎间盘无血管性会阻止临时纤维支架的沉积,而该支架通常有助于软组织修复。椎间盘愈合不良会导致椎间盘损伤积累和慢性炎症,表现为促炎细胞因子和蛋白水解酶过度产生。

方法

从 31 只 Yucatan 小型猪的每只猪的 4 个腰椎间盘中随机选择未处理的对照组;退行性损伤(核切除术);以及核切除术加 FS 注射。动物在手术后 1、2、3、6 和 12 周时被处死。收获椎间盘中枢,以定量评估:(1)形态学和组织学分级的结构;(2)使用 DMMB 测定法的糖胺聚糖组成;(3)使用 ELISA 的细胞因子含量;(4)使用定量压力/容积测试的机械性能。

结果

核切除术椎间盘的环状组织逐渐侵入核,并伴随糖胺聚糖含量减少。相比之下,FS 补充剂抑制了核纤维化并随时间推移促进了糖胺聚糖含量的恢复。FS 椎间盘合成的 TNF-α 明显少于退变椎间盘(66%比 226%,P < 0.05),并在治疗后 2 至 3 周时上调了 IL-4(310%比 166%)和 TGF-β(400%比 117%)。在手术后的第三周,去核椎间盘比对照组的刚度更小(压力模量 779.9 psi 比 2754.8 psi;P < 0.05),且在较低的压力下失效(250.5 psi 比 492.5 psi;P < 0.05)。FS 治疗的椎间盘的刚度和泄漏压力分别在 6 周和 12 周后恢复到对照组的值。

结论

FS 促进了手术损伤的椎间盘的结构、组成和机械修复。这些 FS 衍生的益处可能归因于其传导支架特性以及代谢活跃的成分,如凝血酶、因子 XIII 和抑肽酶乙酸盐。

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