胶原交联剂genipin对大鼠跟腱病模型早期愈合的影响。

IF 2.4 3区医学 Q3 BIOPHYSICS

Journal of biomechanics Pub Date : 2025-09-12 DOI:10.1016/j.jbiomech.2025.112962

Subhajit Konar , Scott M Bolam , Sophia Leung , Mark H Vickers , Jillian Cornish , Dorit Naot , David S Musson

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引用次数: 0

摘要

跟腱病的特点是组织完整性和生物力学性能的恶化。肌腱刚度降低对其功能不利。先前的研究发现，体重增加是跟腱病的一个危险因素。我们的目的是确定胶原交联剂genipin增加受损跟腱的刚度是否可以改善胶原酶诱导的肌腱病变动物模型的早期愈合结果，以及这种效果是否取决于体重。雄性和雌性Sprague-Dawley大鼠在断奶时分别饲喂正常饲粮（ND）和高脂饲粮（HFD）。17周时，每一性别和饮食组分为3个治疗组（n = 15）：胶原酶（CT）、胶原酶-胶原蛋白（CT-GT）和胶原蛋白平（GT）。跟腱内注射胶原酶和胶原蛋白；对侧肌腱作为对照。10天后，收集跟腱进行生物力学和组织学评价。在肌腱病变诱导时，喂食高脂肪饲料的动物平均体重比喂食低脂肪饲料的动物重14.5%。观察胶原酶治疗动物跟腱的生物力学和组织学变化特征。Genipin对肌腱的生物力学和组织学特性没有影响：我们发现GT组和对照组之间没有差异，CT-GT组和CT组之间也没有差异。综上所述，无论动物性别和体重，1 mM genipin均不能改善跟腱病大鼠的生物力学性能，对胶原酶诱导的跟腱病模型的早期肌腱愈合无影响。这是一个重要的临床前发现，可用于指导未来的研究，并防止可能的研究浪费。一个潜在的未来方向是探索创新的递送系统，以维持较高的局部浓度，这可能需要实现这种分子在肌腱愈合中的潜力。

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The effect of the collagen crosslinker genipin on early healing in a rat model of Achilles tendinopathy

Achilles tendinopathy is characterized by deterioration of tissue integrity and biomechanical properties. Reduced tendon stiffness is detrimental to its function. Previous studies found that increased body mass is a risk factor for Achilles tendinopathy. We aimed to determine whether increasing the stiffness of damaged Achilles tendon by the collagen crosslinker genipin can improve early healing outcomes in an animal model of collagenase-induced tendinopathy, and whether the effect depends on body mass.

Male and female Sprague-Dawley rats were allocated to normal diet (ND) or high-fat diet (HFD) at weaning. At 17 weeks, each sex and diet group was divided into three treatment groups (n = 15): collagenase (CT), collagenase-genipin (CT-GT), and genipin (GT). Collagenase and genipin were injected into the Achilles tendons; contralateral tendons served as controls. After 10 days, Achilles tendons were collected for biomechanical and histological evaluation.

At the time of tendinopathy induction, animals fed HFD weighed on average, 14.5 % more than animals on ND. Biomechanical and histological changes characteristic of tendinopathy were observed in Achilles tendons of all animals treated with collagenase. Genipin had no effect on tendon biomechanical and histological properties: we found no differences between the GT and the control group, or between the CT-GT and the CT group.

In conclusion, 1 mM genipin did not improve the biomechanical properties of tendinopathic Achilles, and had no effect on early tendon healing in this rat model of collagenase-induced Achilles tendinopathy, irrespective of animal sex and weight. This is an important pre-clinical finding and can be used to direct future research, and prevent possible research wastage. One potential future direction is exploring innovative delivery systems to maintain higher local concentrations of genipin, that may be required to realize the potential of this molecule in tendon healing.

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来源期刊

Journal of biomechanics 生物-工程：生物医学

CiteScore

5.10

自引率

4.20%

发文量

345

审稿时长

1 months

期刊介绍： The Journal of Biomechanics publishes reports of original and substantial findings using the principles of mechanics to explore biological problems. Analytical, as well as experimental papers may be submitted, and the journal accepts original articles, surveys and perspective articles (usually by Editorial invitation only), book reviews and letters to the Editor. The criteria for acceptance of manuscripts include excellence, novelty, significance, clarity, conciseness and interest to the readership. Papers published in the journal may cover a wide range of topics in biomechanics, including, but not limited to: -Fundamental Topics - Biomechanics of the musculoskeletal, cardiovascular, and respiratory systems, mechanics of hard and soft tissues, biofluid mechanics, mechanics of prostheses and implant-tissue interfaces, mechanics of cells. -Cardiovascular and Respiratory Biomechanics - Mechanics of blood-flow, air-flow, mechanics of the soft tissues, flow-tissue or flow-prosthesis interactions. -Cell Biomechanics - Biomechanic analyses of cells, membranes and sub-cellular structures; the relationship of the mechanical environment to cell and tissue response. -Dental Biomechanics - Design and analysis of dental tissues and prostheses, mechanics of chewing. -Functional Tissue Engineering - The role of biomechanical factors in engineered tissue replacements and regenerative medicine. -Injury Biomechanics - Mechanics of impact and trauma, dynamics of man-machine interaction. -Molecular Biomechanics - Mechanical analyses of biomolecules. -Orthopedic Biomechanics - Mechanics of fracture and fracture fixation, mechanics of implants and implant fixation, mechanics of bones and joints, wear of natural and artificial joints. -Rehabilitation Biomechanics - Analyses of gait, mechanics of prosthetics and orthotics. -Sports Biomechanics - Mechanical analyses of sports performance.