Ewald Timothy J, Walker Justin A, Lewallen Eric A, Trousdale William H, Yaszemski Michael J, Hanssen Arlen D, Morrey Bernard F, van Wijnen Andre J, Sanchez-Sotelo Joaquin, Morrey Mark E, Abdel Matthew P
1 United States Air Force , Luke Air Force Base, Arizona.
2 Reno Orthopaedic Clinic , Reno, Nevada.
Tissue Eng Part C Methods. 2016 Oct;22(10):991-998. doi: 10.1089/ten.TEC.2016.0209.
Implantable biomaterials supporting extended release of pharmacologic agents may permit localized intra-articular delivery of drugs that modulate the fibrotic response to injuries and surgery. Oligo[poly (ethylene glycol)] fumarate (OPF) is an attractive organic carrier, but its safety profile within synovial joints remains unclear. Here, we assessed the safety of OPF sponges using a validated in vivo model of knee arthrofibrosis. A cohort of 102 rabbits was divided into five groups: arthrotomy only (24), arthrotomy with OPF scaffold placement (24), surgically induced contracture (24), surgically induced contracture with OPF scaffold placement (24), and control without any surgical intervention (6). Six rabbits per surgical group were sacrificed at 72 h, 2, 8, and 24 weeks. Outcomes included biomechanical testing of range of motion, histologic analysis of synovial and cartilage tissues, and scaffold degradation. Cartilage histology and biomechanical measurements were comparable between groups with and without OPF. Synovial inflammation scores were similar among most groups with a minimally elevated score in the rabbits with arthrotomy and OPF versus those with arthrotomy alone. Scores for synovial tissues in rabbits with contracture and OPF were clinically equivalent to those with contractures alone. Most animals (92%) retained scaffold fragments at 24 weeks. Thus, OPF scaffolds implanted into native or arthrofibrotic rabbit knees neither induce nor aggravate cartilage damage, synovial inflammation, or contractures. The apparent safety of OPF scaffolds suggests that they are suitable carriers for the controlled delivery of reagents into the intra-articular joint space to treat arthrofibrosis.
支持药物缓释的可植入生物材料或许能够实现药物的局部关节内递送，这些药物可调节对损伤和手术的纤维化反应。聚乙二醇富马酸酯寡聚物（OPF）是一种有吸引力的有机载体，但其在滑膜关节内的安全性尚不明确。在此，我们使用经过验证的膝关节纤维化体内模型评估了OPF海绵的安全性。将102只兔子分为五组：仅进行关节切开术（24只）、关节切开术并放置OPF支架（24只）、手术诱导挛缩（24只）、手术诱导挛缩并放置OPF支架（24只）以及无任何手术干预的对照组（6只）。每个手术组在72小时、2周、8周和24周时处死6只兔子。观察指标包括活动范围的生物力学测试、滑膜和软骨组织的组织学分析以及支架降解情况。有无OPF的组间软骨组织学和生物力学测量结果具有可比性。大多数组的滑膜炎症评分相似，关节切开术联合OPF的兔子的评分略高于仅进行关节切开术的兔子。挛缩联合OPF的兔子的滑膜组织评分在临床上与单纯挛缩的兔子相当。大多数动物（92%）在24周时保留有支架碎片。因此，植入正常或纤维化兔膝关节的OPF支架既不会诱导也不会加重软骨损伤、滑膜炎症或挛缩。OPF支架明显的安全性表明，它们是将试剂可控递送至关节内间隙以治疗关节纤维化的合适载体。
