Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Jiayi Wu, Feifei Li, Peng Yu, Changhao Yu, Chuyi Han, Yitian Wang, Fanyuan Yu, Ling Ye
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Abstract

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration. Despite extensive studies on mineralized parenchymal tissue rebuilding, regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet. Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage. But to date, the absence of promising therapeutic biomaterials/scaffolds remains. The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds. To address these issues, in this study, we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds. Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses. A feasible scaffold, polylactic acid electrospinning membrane (PLA), was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center, meanwhile supporting proper osteointegration with defect bony edges. Especially, transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered. This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing, offering clinicians potential choices for regenerating such complicated injuries.

Abstract Image

支架诱导缝合间充质再生的转录组和细胞解码
精确协调细胞命运决定是基于支架的骨骼再生成功的基础。尽管对矿化实质组织重建进行了广泛研究,但再生和维持钙骨内未分化间充质仍极具挑战性,进展有限。现有知识证明,重建缝间充质干细胞龛对避免严重的脑损伤甚至系统性损伤是不可或缺的。但迄今为止,仍缺乏有前景的治疗生物材料/支架。究其原因,在于缺乏了解支架细胞命运调控的基础知识和方法证据。为了解决这些问题,在本研究中,我们系统地研究了不同类型的常用腓骨支架对细胞命运的决定作用和转录组机制。我们的数据阐明了无支架移植的自然过程,并展示了不同支架如何改变体内细胞反应。接下来,我们确定了一种可行的支架--聚乳酸电纺丝膜(PLA),它能精确控制间充质的生长和自我更新,在缺损中心重建非骨质生成的缝合线样组织,同时支持与缺损骨边缘的适当骨整合。特别是,该研究通过转录组分析,破译了 PLA 精心策划的细胞命运决定的细胞机制。这项研究首次从细胞角度解读了缝合骨复合体缺损愈合过程中支架的命运调控,为临床医生再生此类复杂损伤提供了可能的选择。
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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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