Development of a novel rat long-bone nonunion model and efficacy evaluation of a prostaglandin EP4 selective agonist (AKDS001) combined with iliac bone grafting.

IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING
Daisuke Tateiwa, Masahiro Nishida, Joe Kodama, Hiromasa Hirai, Shinichi Nakagawa, Yuichiro Ukon, Kazuhiro Takeyama, Natsumi Yamamori, Kyoko Hirano, Masato Ikuta, Takayuki Kitahara, Takuya Furuichi, Masayuki Bun, Seiji Okada, Takashi Kaito
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引用次数: 0

Abstract

Aims: Nonunion occurs when a fracture fails to heal permanently, often necessitating surgical intervention to stimulate the bone healing response. Current animal models of long-bone nonunion do not adequately replicate human pathological conditions. This study was intended as a preliminary investigation of a novel rat nonunion model using a two-stage surgical intervention, and to evaluate the efficacy of a selective prostaglandin E2 receptor 4 agonist (AKDS001) as a novel nonunion therapeutic agent compared with existing treatments.

Methods: Initially, Sprague-Dawley rats underwent intramedullary Kirschner wire (K-wire) fixation of a femoral fracture with the interposition of a 2 mm-thick silicon disc. After three weeks, the silicon disc was removed, and the intramedullary K-wire was replaced with plate fixation while maintaining the 2 mm defect. Contrary to the control group (1) that received no treatment, the following therapeutic interventions were performed at injury sites after freshening: (2) freshening group: no grafting; (3) iliac bone (IB) group: IB grafting; (4) AKDS group: AKDS001-loaded microspheres (MS) combined with IB (0.75 mg/ml); and (5) bone morphogenetic protein (BMP) group: grafting of a BMP-2-loaded collagen sponge (10 μg; 0.10 mg/ml). After six weeks, micro-CT (μCT) and histological analysis was performed.

Results: In the control group, the radiological union rate was 0%, and histological findings showed that fracture sites comprised fibrous scar tissue, resembling the histology of human nonunion. The union rates in the freshening, IB, AKDS, and BMP groups were 16.7%, 0%, 62.5%, and 50.0%, respectively. The AKDS group demonstrated a significantly higher union rate than the IB group (p = 0.026). μCT and histological analysis indicated that the quality of newly formed bone was superior in the AKDS group than in the BMP group.

Conclusion: We developed a novel long-bone nonunion model. The co-therapy of AKDS001-MS and IB grafting presents a promising new treatment for nonunion.

新型大鼠长骨不连模型的建立及前列腺素EP4选择性激动剂(AKDS001)联合髂骨移植的疗效评价。
目的:骨折不能永久愈合时发生骨不连,通常需要手术干预来刺激骨愈合反应。目前长骨不连的动物模型不能充分地复制人类的病理情况。本研究旨在对一种采用两阶段手术干预的新型大鼠骨不连模型进行初步研究,并评估选择性前列腺素E2受体4激动剂(AKDS001)作为一种新型骨不连治疗剂与现有治疗方法的疗效。方法:首先,Sprague-Dawley大鼠髓内克氏针(k -丝)内固定股骨骨折,中间置入2mm厚的硅盘。三周后,取出硅椎间盘,在保持2mm缺损的同时,用钢板固定代替髓内k线。与对照组(1)不进行治疗相反,在损伤部位进行以下治疗干预:(2)新鲜组:不移植;(3)髂骨(IB)组:IB移植;(4) AKDS组:载akds001微球(MS)联合IB (0.75 mg/ml);(5)骨形态发生蛋白(BMP)组:载BMP-2胶原海绵(10 μg;0.10毫克/毫升)。6周后进行显微ct (μCT)和组织学分析。结果:对照组放射学愈合率为0%,组织学结果显示骨折部位由纤维瘢痕组织组成,类似于人类骨不愈合的组织学。新生组、IB组、AKDS组和BMP组的愈合率分别为16.7%、0%、62.5%和50.0%。AKDS组愈合率显著高于IB组(p = 0.026)。μCT和组织学分析表明,AKDS组新生骨质量优于BMP组。结论:我们建立了一种新的长骨不连模型。AKDS001-MS联合IB移植是治疗骨不连的新方法。
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来源期刊
Bone & Joint Research
Bone & Joint Research CELL & TISSUE ENGINEERING-ORTHOPEDICS
CiteScore
7.40
自引率
23.90%
发文量
156
审稿时长
12 weeks
期刊介绍: The gold open access journal for the musculoskeletal sciences. Included in PubMed and available in PubMed Central.
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