Collagen scaffold-seeded iTenocytes accelerate the healing and functional recovery of Achilles tendon defects in a rat model.

IF 4.3 3区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Frontiers in Bioengineering and Biotechnology Pub Date : 2024-12-06 eCollection Date: 2024-01-01 DOI:10.3389/fbioe.2024.1407729
Thomas Später, Patricia Del Rio, Oksana Shelest, Jacob T Wechsler, Giselle Kaneda, Melissa Chavez, Julia Sheyn, Victoria Yu, Wolfgang Metzger, Dave Huang, Melodie Metzger, Wafa Tawackoli, Dmitriy Sheyn
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Abstract

Introduction: Tendon injuries represent an ongoing challenge in clinical practice due to poor regenerative capacity, structure, and biomechanical function recovery of ruptured tendons. This study is focused on the assessment of a novel strategy to repair ruptured Achilles tendons in a Nude rat model using stem cell-seeded biomaterial.

Methods: Specifically, we have used induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) overexpressing the early tendon marker Scleraxis (SCX, iMSCSCX+, iTenocytes) in combination with an elastic collagen scaffold. Achilles tendon defects in Nude rat models were created by isolating the tendon and excising 3 mm of the midsection. The Achilles tendon defects were then repaired with iTenocyte-seeded scaffolds, unseeded scaffolds, or suture only and compared to native Nude rat tendon tissue using gait analyses, biomechanical testing, histology, and immunohistochemistry.

Results: The results show faster functional recovery of gait in iTenocyte-seeded scaffold group comparing to scaffold only and suture only groups. Both iTenocyte-seeded scaffold and scaffold only treatment groups had improved biomechanical properties when compared to suture only treatment group, however no statistically significant difference was found in comparing the cell seeding scaffold an scaffold only group in terms of biomechanical properties. Immunohistochemistry staining further demonstrated that iTenocytes successfully populated the collagen scaffolds and survived 9 weeks after implantation in vivo. Additionally, the repaired tissue of iTenocyte-treated injuries exhibited a more organized structure when compared to tendon defects that were repaired only with suturing or unseeded scaffolds.

Conclusion: We suggest that iTenocyte-seeded DuRepair™ collagen scaffold can be used as potential treatment to regenerate the tendon tissue biomechanically and functionally.

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胶原支架细胞加速大鼠跟腱缺损的愈合和功能恢复。
简介:由于肌腱断裂的再生能力、结构和生物力学功能恢复较差,肌腱损伤在临床实践中一直是一个挑战。本研究的重点是评估一种在裸鼠模型中使用干细胞种子生物材料修复断裂跟腱的新策略。方法:具体来说,我们将诱导多能干细胞(iPSC)衍生的间充质干细胞(iMSCs)过度表达早期肌腱标记物Scleraxis (SCX, iMSCSCX+, iTenocytes)与弹性胶原支架结合使用。裸鼠跟腱缺损模型采用分离跟腱并切除中段3mm的方法。然后用itenocyte -种子支架、非种子支架或仅缝合修复跟腱缺损,并通过步态分析、生物力学测试、组织学和免疫组织化学与天然裸鼠肌腱组织进行比较。结果:与单纯支架组和单纯缝线组相比,itenocyte -种子支架组步态功能恢复更快。itenocyte -seed - scaffold处理组和支架单独处理组的生物力学性能均优于缝线单独处理组,但细胞播种支架和支架单独处理组的生物力学性能差异无统计学意义。免疫组织化学染色进一步表明,iTenocytes成功填充胶原支架,并在植入后存活9周。此外,与仅使用缝合或未植入支架修复的肌腱缺损相比,itenocyte修复的损伤组织显示出更有组织的结构。结论:itenocyte -seed DuRepair™胶原支架可作为肌腱组织生物力学和功能再生的潜在治疗方法。
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来源期刊
Frontiers in Bioengineering and Biotechnology
Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering
CiteScore
8.30
自引率
5.30%
发文量
2270
审稿时长
12 weeks
期刊介绍: The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.
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