探索脊柱融合的创新增强策略：一种新的选择性前列腺素EP4受体激动剂作为潜在的骨促进因子来增强腰椎后外侧融合

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-03-19 DOI:10.1016/j.biomaterials.2025.123278

Lisa Findeisen , Xinggui Tian , Corina Vater , Deepak Bushan Raina , Hannes Kern , Julia Bolte , Luisa Straßburger , Lucas-Maximilian Matuszewski , Niels Modler , Robert Gottwald , Anja Winkler , Klaus-Dieter Schaser , Alexander C. Disch , Stefan Zwingenberger

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引用次数: 0

摘要

生物活性药物的现场递送有助于提高脊柱融合术的有效性。然而，目前在临床实践中使用的fda批准的药物受到副作用和成本问题的限制，迫切需要探索新的替代品。目的研究具有骨促进作用的新型前列腺素EP4受体激动剂KMN-159在脊柱后侧融合（PLF）手术中的疗效。方法采用矿化胶原基质（MCM）支架局部给药不同剂量的KMN-159，比较其与fda批准的重组人骨形态发生蛋白2 （rhBMP-2）在大鼠腰椎PLF模型中的疗效。选取10周龄雄性Wistar大鼠192只，随机分为8组：1)SHAM, 2) MCM, 3) MCM +10 μg rhBMP-2（每个支架），4-8)MCM + 0.1、1、10、100或1000 μg KMN-159（每个支架）。在L4-5节段进行PLF手术，动物在3周和6周后安乐死以评估脊柱融合。结果skmn -159对MCM携带者的成骨细胞、破骨细胞和血管长入具有剂量依赖性的促骨作用，并以剂量依赖性的方式导致新骨形成。中、高剂量KMN-159（10、100、1000 μg）组显著增强PLF，生物力学改善，而低剂量（0.1、1 μg）组不足以实现腰椎融合。结论kmn -159作为一种新型的骨促进因子，与其功能化的MCM支架结合，是一种潜在的提高PLF手术效果的生物活性材料。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Exploring an innovative augmentation strategy in spinal fusion: A novel selective prostaglandin EP4 receptor agonist as a potential osteopromotive factor to enhance lumbar posterolateral fusion

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Exploring an innovative augmentation strategy in spinal fusion: A novel selective prostaglandin EP4 receptor agonist as a potential osteopromotive factor to enhance lumbar posterolateral fusion

Background

On-site delivery of bioactive agents facilitates enhancing the effectiveness of spinal fusion. However, the FDA-approved agents currently used in clinical practice are limited by side effects and cost issues, urging exploration of new alternatives.

Aim

This study aimed to investigate the effectiveness of KMN-159, a novel selective prostaglandin EP4 receptor agonist with osteopromotive properties, in spinal posterolateral fusion (PLF) surgery.

Methods

Various doses of KMN-159 were delivered locally using a mineralized collagen matrix (MCM) scaffold, and its efficacy results were compared with FDA-approved recombinant human bone morphogenetic protein-2 (rhBMP-2) in a rat lumbar PLF model. 192 male Wistar rats, aged 10 weeks, were randomized into 8 groups: 1) SHAM, 2) MCM, 3) MCM +10 μg rhBMP-2 (per scaffold), 4–8) MCM + 0.1, 1, 10, 100 or 1000 μg KMN-159 (per scaffold). PLF surgery was performed at the L4-5 level, and animals were euthanized after 3 and 6 weeks for spinal fusion evaluation.

Results

KMN-159 exhibited dose-dependent osteopromotive effects on osteoblasts, osteoclasts, and vascular ingrowth within MCM carriers, resulting in new bone formation in a dose-dependent manner. The mid- and high-dose KMN-159 (10, 100, and 1000 μg) groups significantly enhanced PLF with biomechanical improvement, while low-dose (0.1 and 1 μg) groups were insufficient to achieve lumbar fusion.

Conclusion

KMN-159 emerges as a novel osteopromotive factor, coupled with its functionalized MCM scaffold presents a potential bioactive material for enhancing PLF surgery outcomes.

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.