Kabuto Yukichi, Morihara Toru, Sukenari Tsuyoshi, Kida Yoshikazu, Oda Ryo, Arai Yuji, Sawada Koshiro, Matsuda Ken-Ichi, Kawata Mitsuhiro, Tabata Yasuhiko, Fujiwara Hiroyoshi, Kubo Toshikazu
1 Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto, Japan .
2 Department of Anatomy and Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto, Japan .
Tissue Eng Part A. 2015 Jul;21(13-14):2025-33. doi: 10.1089/ten.TEA.2014.0541. Epub 2015 May 12.
Bone morphogenetic protein-7 (BMP-7) promotes not only osteogenesis but also matrix production in chondrocytes and tenocytes. However, because of its short half-life, maintaining local concentrations of BMP-7 is difficult. We examined the use of a gelatin hydrogel sheet (GHS) for the sustained release of BMP-7 in stimulating rotator cuff repair at the tendon-to-bone insertion. Twelve-week-old male Sprague-Dawley rats were used. Radiolabeled BMP-7 ((125)I-BMP-7) was injected into the subacromial bursa in the (125)I-BMP-7 group, whereas a GHS impregnated with (125)I-BMP-7 was implanted on the tendon attached to the tendon-to-bone insertion in the (125)I-BMP-7+GHS group. Levels of (125)I-BMP-7 in the tendon-to-bone insertion were assessed at 1, 3, 7, 14, and 21 postoperative days. The BMP-7 concentrations were significantly higher in the (125)I-BMP-7+GHS group than in the (125)I-BMP-7 group. Next, the bilateral supraspinatus tendons were resected and sutured to the greater tuberosity of the humerus using the Mason-Allen technique. Treatment groups were created as follows: either phosphate-buffered saline (PBS) or BMP-7 was injected into the subacromial bursa in the PBS and BMP-7 groups, whereas a GHS impregnated with either PBS or BMP-7 was implanted on the repaired tendon attached to the tendon-to-bone insertion in the PBS+GHS and BMP-7+GHS groups. The resected specimens were stained at 2, 4, and 8 postoperative weeks with hematoxylin and eosin as well as Safranin O, and tissue repair was evaluated histologically by using the tendon-to-bone maturing score. Tissue repair was assessed biomechanically at 4 and 8 postoperative weeks. The BMP-7+GHS group at 8 postoperative weeks demonstrated a favorable cartilage matrix production and tendon orientation; moreover, the tendon-to-bone maturing score and the ultimate force-to-failure were the highest in this group. The ability of GHS to provide controlled release of various growth factors has been previously reported. We confirmed that the GHS releases BMP-7 in a sustained manner in the rat shoulder joint. At 8 postoperative weeks, the repaired tissue was mostly restored, both histologically and biomechanically, in the BMP-7+GHS group. We therefore conclude that the sustained release of BMP-7 from a GHS can stimulate rotator cuff repair.
骨形态发生蛋白-7(BMP-7)不仅能促进成骨,还能促进软骨细胞和肌腱细胞的基质生成。然而,由于其半衰期短,维持BMP-7的局部浓度很困难。我们研究了使用明胶水凝胶片(GHS)来持续释放BMP-7,以刺激肌腱-骨连接处的肩袖修复。使用12周龄的雄性Sprague-Dawley大鼠。在125I-BMP-7组中,将放射性标记的BMP-7(125I-BMP-7)注入肩峰下囊,而在125I-BMP-7+GHS组中,将浸渍有125I-BMP-7的GHS植入附着于肌腱-骨连接处的肌腱上。在术后1、3、7、14和21天评估肌腱-骨连接处的125I-BMP-7水平。125I-BMP-7+GHS组中的BMP-7浓度显著高于125I-BMP-7组。接下来,切除双侧冈上肌腱,并使用梅森-艾伦技术将其缝合至肱骨大结节。治疗组如下创建:在PBS组和BMP-7组中,将磷酸盐缓冲盐水(PBS)或BMP-7注入肩峰下囊,而在PBS+GHS组和BMP-7+GHS组中,将浸渍有PBS或BMP-7的GHS植入附着于肌腱-骨连接处的修复肌腱上。在术后2、4和8周,将切除的标本用苏木精和伊红以及番红O染色,并使用肌腱-骨成熟评分进行组织学评估组织修复情况。在术后4和8周进行生物力学评估组织修复情况。术后8周时,BMP-7+GHS组显示出良好的软骨基质生成和肌腱排列;此外,该组的肌腱-骨成熟评分和极限破坏力最高。先前已有报道GHS具有控制释放各种生长因子的能力。我们证实GHS在大鼠肩关节中以持续方式释放BMP-7。术后8周时,BMP-7+GHS组的修复组织在组织学和生物力学方面大多已恢复。因此,我们得出结论,GHS持续释放BMP-7可刺激肩袖修复。