Galatz Leesa M, Sandell Linda J, Rothermich Stefan Y, Das Rosalina, Mastny Ava, Havlioglu Necat, Silva Matthew J, Thomopoulos Stavros
Department of Orthopaedic Research, Washington University School of Medicine, Barnes-Jewish Hospital, 660 S. Euclid Avenue, Campus Box 8233, St. Louis, Missouri 63110, USA.
J Orthop Res. 2006 Mar;24(3):541-50. doi: 10.1002/jor.20067.
Rotator cuff repair is known to have a high failure rate. Little is known about the natural healing process of the rotator cuff repair site, hence little can be done to improve the tendon's ability to heal. The purpose of this study was to investigate the collagen formation at the early repair site and to localize TGFbeta-1 and 3 during early healing and compare their levels to cell proliferation and histological changes. Bilateral supraspinatus tendons were transected and repaired in 60 rats. Specimens were harvested and evaluated at 0, 1, 3, 7, 10, 28, and 56 days. Histological sections were evaluated for cell morphology. Immunohistochemistry and in situ hybridization was performed to localize protein and mRNA for collagen types I and III and TGFbeta-1 and 3. Proliferating cell nuclear antigen (PCNA) assay was performed to measure cell proliferation, and cells were counted to determine cell density. Biomechanical properties were evaluated. Repair tissue demonstrated an initial inflammatory response with multinucleated cells present at 1 and 3 days, and lymphocytes and plasma cells presents at 7 and 10 days. Capillary proliferation began at 3 days and peaked at 10 days. Ultimate force increased significantly over the time period studied. Collagen I protein and mRNA significantly increased at 10 days, and reached a plateau by 28 and 56 days. Collagen III showed a similar trend, with an early increase, and remained high until 56 days. TGFbeta-1 was localized to the forming scar tissue and showed a distinct peak at 10 days. TGFbeta-3 was not seen at the healing insertion site. Cell proliferation and density followed the same trend as TGFbeta-1. A wound healing response does occur at the healing rotator cuff insertion site, however, the characteristics of the tendon after healing differ significantly from the uninjured tendon insertion site at the longest time-point studied. A distinctive collagen remodeling process occurred with an initial increase in the formation of collagen types I and III followed by a decrease toward baseline levels seen at time 0. Growth factor TGFbeta-1 was localized to repair tissue and coincided with a peak in cell proliferation and cellularity. Repair sites remained unorganized histologically and biomechanically inferior in comparison to previously described uninjured insertion sites.
已知肩袖修复的失败率很高。关于肩袖修复部位的自然愈合过程知之甚少，因此几乎无法采取措施提高肌腱的愈合能力。本研究的目的是调查早期修复部位的胶原蛋白形成情况，在早期愈合过程中定位转化生长因子β-1（TGFbeta-1）和转化生长因子β-3（TGFbeta-3），并将它们的水平与细胞增殖和组织学变化进行比较。在60只大鼠中切断并修复双侧冈上肌腱。在0、1、3、7、10、28和56天采集标本并进行评估。对组织学切片进行细胞形态学评估。进行免疫组织化学和原位杂交以定位I型和III型胶原蛋白以及TGFbeta-1和TGFbeta-3的蛋白质和信使核糖核酸（mRNA）。进行增殖细胞核抗原（PCNA）检测以测量细胞增殖，并对细胞进行计数以确定细胞密度。评估生物力学特性。修复组织表现出最初的炎症反应，在第1天和第3天出现多核细胞，在第7天和第10天出现淋巴细胞和浆细胞。毛细血管增殖在第3天开始并在第10天达到峰值。在所研究的时间段内，极限力显著增加。I型胶原蛋白的蛋白质和mRNA在第10天显著增加，并在第28天和第56天达到平台期。III型胶原蛋白呈现类似趋势，早期增加，并一直保持在较高水平直至第56天。TGFbeta-1定位于形成的瘢痕组织，并在第10天出现明显峰值。在愈合的附着部位未观察到TGFbeta-3。细胞增殖和密度与TGFbeta-1的趋势相同。在愈合的肩袖附着部位确实发生了伤口愈合反应，然而，在研究的最长时间点，愈合后的肌腱特征与未受伤的肌腱附着部位有显著差异。随着I型和III型胶原蛋白形成的最初增加，随后朝着第0天时所见的基线水平下降，发生了独特的胶原蛋白重塑过程。生长因子TGFbeta-1定位于修复组织，并与细胞增殖和细胞数量的峰值同时出现。与先前描述的未受伤附着部位相比，修复部位在组织学上仍然无组织，并且生物力学性能较差。
