Skeletal muscle injury treatment using the Silk Elastin® injection in a rat model

IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Regenerative Therapy Pub Date : 2024-06-01 DOI:10.1016/j.reth.2024.05.012
Kyohei Nakata , Masakazu Ishikawa , Naosuke Kamei , Shigeru Miyaki , Nobuo Adachi , Keiichiro Inoue , Shingo Kawabata
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Abstract

Background

Skeletal muscle injury (SMI) is often treated conservatively, although it can lead to scar tissue formation, which impedes muscle function and increases muscle re-injury risk. However, effective interventions for SMIs are yet to be established.

Hypothesis

The administration of Silk Elastin® (SE), a novel artificial protein, to the SMI site can suppress scar formation and promote tissue repair.

Study design

A controlled laboratory study.

Methods

In vitro: Fibroblast migration ability was assessed using a scratch assay. SE solution was added to the culture medium, and the fibroblast migration ability was compared across different concentrations. In vivo: An SMI model was established with Sprague–Dawley rats, which were assigned to three groups based on the material injected to the SMI site: SE gel (SE group; n = 8), atelocollagen gel (Atelo group; n = 8), and phosphate buffer saline (PBS group; n = 8). Histological evaluations were performed at weeks 1 and 4 following the SMI induction. In the 1-week model, we detected the expression of transforming growth factor (TGF)-β1 in the stroma using immunohistological evaluation and real-time polymerase chain reaction analysis. In the 4-week model, we measured tibialis anterior muscle strength upon peroneal nerve stimulation as a functional assessment.

Results

In vitro: The fibroblast migration ability was suppressed by SE added at a concentration of 10⁴ μg/mL in the culture medium. In vivo: In the 1-week model, the SE group exhibited significantly lower TGFβ −1 expression than the PBS group. In the 4-week model, the SE group had a significantly larger regenerated muscle fiber diameter and smaller scar formation area ratio than the other two groups. Moreover, the SE group was superior to the other two groups in terms of regenerative muscle strength.

Conclusion

Injection of SE gel to the SMI site may inhibit tissue scarring by reducing excessive fibroblast migration, thereby enhancing tissue repair.

Clinical relevance

The findings of this study may contribute to the development of an early intervention method for SMIs.

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在大鼠模型中使用 Silk Elastin® 注射液治疗骨骼肌损伤
背景骨骼肌损伤(SMI)通常采用保守疗法,但会导致瘢痕组织形成,从而阻碍肌肉功能并增加肌肉再次损伤的风险。研究设计 实验室对照研究方法体外试验:采用划痕试验评估成纤维细胞的迁移能力。在培养基中加入 SE 溶液,比较不同浓度的成纤维细胞迁移能力。体内:用 Sprague-Dawley 大鼠建立 SMI 模型,根据注射到 SMI 位点的材料将其分为三组:SE凝胶(SE组;n = 8)、elocollagen凝胶(Atelo组;n = 8)和磷酸盐缓冲盐水(PBS组;n = 8)。在诱导 SMI 后的第 1 周和第 4 周进行组织学评估。在 1 周模型中,我们使用免疫组织学评估和实时聚合酶链反应分析检测基质中转化生长因子(TGF)-β1 的表达。在为期 4 周的模型中,我们测量了腓肠神经刺激时的胫骨前肌力,作为功能评估:在培养基中添加浓度为 10⁴ μg/mL 的 SE 可抑制成纤维细胞的迁移能力。体内:在 1 周模型中,SE 组的 TGFβ -1 表达明显低于 PBS 组。在 4 周模型中,SE 组的再生肌纤维直径明显大于其他两组,瘢痕形成面积比明显小于其他两组。此外,SE 组在再生肌力方面优于其他两组。结论在 SMI 位点注射 SE 凝胶可通过减少成纤维细胞的过度迁移来抑制组织瘢痕的形成,从而增强组织修复。
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来源期刊
Regenerative Therapy
Regenerative Therapy Engineering-Biomedical Engineering
CiteScore
6.00
自引率
2.30%
发文量
106
审稿时长
49 days
期刊介绍: Regenerative Therapy is the official peer-reviewed online journal of the Japanese Society for Regenerative Medicine. Regenerative Therapy is a multidisciplinary journal that publishes original articles and reviews of basic research, clinical translation, industrial development, and regulatory issues focusing on stem cell biology, tissue engineering, and regenerative medicine.
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