Sakiyama-Elbert Shelly E, Das Rosalina, Gelberman Richard H, Harwood Fredrick, Amiel David, Thomopoulos Stavros
Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, MO, USA.
J Hand Surg Am. 2008 Nov;33(9):1548-57. doi: 10.1016/j.jhsa.2008.05.030.
Surgically repaired intrasynovial tendons are at greatest risk of failure in the first 3 weeks after surgery. Attempts to improve the strength of repair by modifying rehabilitation parameters have not always been successful. Manipulation of the biological environment of the sutured tendon holds great promise for accelerating the repair process. The goals of this study were to examine (1) the range of conditions (eg, dosage, delivery system formulation, presence of cells) over which delivery of platelet-derived growth factor-BB (PDGF-BB) can be sustained from fibrin matrices using a heparin-binding delivery system (HBDS) and (2) the biological activity of the PDGF-BB released from this system on canine tendon fibroblasts in vitro.
We examined in vitro release kinetics from cellular and acellular fibrin matrices using enzyme-linked immunosorbent assays. We examined the biologic activity of the PDGF-BB in vitro by measuring cell proliferation (ie, total DNA) and collagen synthesis (ie, proline incorporation).
The acellular release kinetics of PDGF-BB was modulated by varying the ratio of PDGF-BB to heparin (PDGF-binding sites) or the dose of PDGF-BB in the presence of the delivery system. In the presence of canine tendon fibroblasts, the delivery system prolonged the duration of PDGF-BB release from fibrin matrices, thus demonstrating that cells are able to liberate PDGF-BB retained by the HBDS. Sustained delivery of PDGF-BB promoted increased cell proliferation at doses of 0.125 microg/mL and 1.25 microg/mL compared to fibrin without delivery system. Collagen synthesis was enhanced by PDGF-BB at doses of 0.125 microg/mL and 1.25 microg/mL; however, there was an enhancement over fibrin without the delivery system only at the lower dose.
These results demonstrate that the PDGF-BB released from fibrin matrices containing an HBDS is biologically active and can modulate both cell proliferation and extracellular matrix synthesis, both of which are key factors in the process of tendon repair.
手术修复的滑膜内肌腱在术后最初3周内发生断裂的风险最高。试图通过调整康复参数来提高修复强度的尝试并非总能成功。调控缝合肌腱的生物环境对于加速修复过程具有很大的前景。本研究的目的是考察：（1）使用肝素结合递送系统（HBDS）从纤维蛋白基质中持续递送血小板衍生生长因子-BB（PDGF-BB）的条件范围（如剂量、递送系统配方、细胞存在情况）；（2）该系统释放的PDGF-BB对犬肌腱成纤维细胞的体外生物学活性。
我们使用酶联免疫吸附测定法检测了细胞性和无细胞性纤维蛋白基质的体外释放动力学。我们通过测量细胞增殖（即总DNA）和胶原蛋白合成（即脯氨酸掺入）来检测PDGF-BB的体外生物学活性。
在递送系统存在的情况下，通过改变PDGF-BB与肝素（PDGF结合位点）的比例或PDGF-BB的剂量，可调节PDGF-BB的无细胞释放动力学。在犬肌腱成纤维细胞存在的情况下，递送系统延长了PDGF-BB从纤维蛋白基质中的释放持续时间，从而表明细胞能够释放被HBDS保留的PDGF-BB。与无递送系统的纤维蛋白相比，在0.125μg/mL和1.25μg/mL剂量下，PDGF-BB的持续递送促进了细胞增殖增加。在0.125μg/mL和1.25μg/mL剂量下，PDGF-BB增强了胶原蛋白合成；然而，仅在较低剂量下，与无递送系统的纤维蛋白相比才有增强。
这些结果表明，从含有HBDS的纤维蛋白基质中释放的PDGF-BB具有生物学活性，并且可以调节细胞增殖和细胞外基质合成，这两者都是肌腱修复过程中的关键因素。
