Arsoy Diren, Salib Christopher G, Trousdale William H, Tibbo Meagan E, Limberg Afton K, Viste Anthony, Lewallen Eric A, Reina Nicolas, Yaszemski Michael J, Berry Daniel J, van Wijnen Andre J, Morrey Mark E, Sanchez-Sotelo Joaquin, Abdel Matthew P
Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905.
J Orthop Res. 2018 Nov;36(11):2949-2955. doi: 10.1002/jor.24068. Epub 2018 Jul 13.
Trauma, surgery, and other inflammatory conditions can lead to debilitating joint contractures. Adjunct pharmacologic modalities may permit clinical prevention and treatment of recalcitrant joint contractures. We investigated the therapeutic potential of rosiglitazone by intra-articular delivery via oligo[poly(ethylene glycol)fumarate] (OPF) hydrogels in an established rabbit model of arthrofibrosis. OPF hydrogels loaded with rosiglitazone were characterized for drug elution properties upon soaking in minimum essential media (MEM) with 10% fetal bovine serum and measurements of drug concentrations via High Performance Liquid Chromatography (HPLC). Drug-loaded scaffolds were surgically implanted into 24 skeletally mature female New Zealand White rabbits that were divided into equal groups receiving OPF hydrogels loaded with rosiglitazone (1.67 mg), or vehicle control (10 µl DMSO). After 8 weeks of joint immobilization, rabbits were allowed unrestricted cage activity for 16 weeks. Contracture angles of rabbit limbs treated with rosiglitazone showed statistically significant improvements in flexion compared to control animals (mean angles, respectively, 64.4° vs. 53.3°, p < 0.03). At time of sacrifice (week 24), animals in the rosiglitazone group continued to exhibit less joint contracture than controls (119.0° vs. 99.5°, p = 0.014). The intra-articular delivery of rosiglitazone using implanted OPF hydrogels decreases flexion contractures in a rabbit model of arthrofibrosis without causing adverse effects (e.g., gross inflammation or arthritis). Statement of Clinical Significance: Post-traumatic joint contractures are common and debilitating, with limited available treatment options. Pharmacologic interventions can potentially prevent and treat such contractures. This study is translational in that a commercially approved medication has been repurposed through a novel delivery device. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2949-2955, 2018.
创伤、手术及其他炎症性疾病可导致使人虚弱的关节挛缩。辅助药物治疗方法或许能实现对顽固性关节挛缩的临床预防和治疗。我们通过在已建立的兔关节纤维化模型中经聚（乙二醇）富马酸酯（OPF）水凝胶进行关节内给药，研究了罗格列酮的治疗潜力。将负载罗格列酮的OPF水凝胶浸泡于含10%胎牛血清的最低限度基本培养基（MEM）中，通过高效液相色谱法（HPLC）测定药物浓度，以此表征其药物洗脱特性。将载药支架手术植入24只骨骼成熟的雌性新西兰白兔体内，这些兔子被平均分为两组，分别接受负载罗格列酮（1.67毫克）的OPF水凝胶或赋形剂对照（10微升二甲亚砜）。关节固定8周后，让兔子在笼中自由活动16周。与对照动物相比，用罗格列酮治疗的兔肢体挛缩角度在屈曲方面有统计学上的显著改善（平均角度分别为64.4°对53.3°，p < 0.03）。在处死时（第24周），罗格列酮组动物的关节挛缩仍比对照组少（119.0°对99.5°，p = 0.014）。在兔关节纤维化模型中，使用植入的OPF水凝胶进行关节内递送罗格列酮可减少屈曲挛缩，且不会引起不良反应（如严重炎症或关节炎）。临床意义声明：创伤后关节挛缩常见且使人虚弱，可用的治疗选择有限。药物干预有可能预防和治疗此类挛缩。本研究具有转化意义，因为一种商业上已获批准的药物已通过一种新型给药装置实现了新用途。© 2018骨科研究协会。由威利期刊公司出版。《矫形外科研究杂志》36:2949 - 2955，2018年。
