Repairing a critical cranial defect using WISP1-pretreated chondrocyte scaffolds.

IF 6.7 1区 工程技术 Q1 CELL & TISSUE ENGINEERING
Idan Carmon, Shira Kalmus, Anna Zobrab, Michael Alterman, Raphaelle Emram, May Gussarsky, Leonid Kandel, Eli Reich, Nardi Casap, Mona Dvir-Ginzberg
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引用次数: 1

Abstract

In cranial flat bone fractures, spontaneous bone repair will occur only when the fracture ends are in close contact. However, in cases wherein bone discontinuity is extensive, surgical interventions are often required. To this end, autologous bone is harvested and surgically integrated into the site of fracture. Here we propose to use cartilage, as an alternative autologous source, to promote cranial fracture repair. The advantage of this approach is the potential reduction in donor site morbidity, likely due to the avascular and aneural nature of cartilage. As a first step we attempted to induce cartilage mineralization in vitro, using micromass primary chondrocyte cultures, incubated with BMP2 and/or WISP1, which were examined histologically following a 3-week culture period. Next, chondrocyte seeded collagen scaffolds were evaluated in vitro for expression profiles and ALP activity. Finally, chondrocyte-seeded collagen scaffolds were implanted in a Lewis rats 8 mm critical calvaria defect model, which was imaged via live CT for 12 weeks until sacrifice. End points were analyzed for microCT, histology, and serum levels of bone related markers. Micromass cultures exhibited an osseous inducing trend following WISP1 administration, which was maintained in chondrocyte seeded scaffolds. Accordingly, in vivo analysis was carried out to assess the impact of WISP1-pretreated chondrocytes (WCS) versus untreated chondrocytes (UCS) in calvaria defect model and compared to untreated control comprised of a defect-associated blood clot (BC) or empty collagen scaffold (CS) implant. Live CT and microCT exhibited higher mineralization volumes in critical defect implanted with UCS, with some structural improvements in WCS. Histological analysis exhibited higher anabolic bone formation in WCS and trabecular bone was detected in WCS and UCS groups. Chondrocytes implanted into critical cranial defect expedite the formation of native-like osseous tissue, especially after WISP1 priming in culture. Ultimately, these data support the use of autologous chondrocytes to repair critical maxillofacial defects.

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Abstract Image

Abstract Image

使用wisp1预处理的软骨细胞支架修复严重的颅骨缺损。
在颅扁平骨骨折中,只有当骨折端紧密接触时才会发生自发骨修复。然而,在骨不连续性广泛的情况下,通常需要手术干预。为此,自体骨被采集并通过手术整合到骨折部位。在这里,我们建议使用软骨作为替代的自体来源,以促进颅骨骨折的修复。这种方法的优点是潜在的减少供体部位的发病率,可能是由于软骨的无血管和神经性质。作为第一步,我们尝试在体外诱导软骨矿化,使用微团原代软骨细胞培养物,与BMP2和/或WISP1孵育,在3周的培养期后进行组织学检查。接下来,评估软骨细胞种子胶原支架的体外表达谱和ALP活性。最后,将软骨细胞种子胶原蛋白支架植入Lewis大鼠8 mm严重颅骨缺损模型,通过活体CT成像12周,直至牺牲。终点分析显微ct、组织学和骨相关标志物的血清水平。WISP1给药后,微块培养表现出骨诱导的趋势,这种趋势在软骨细胞植入支架中得以维持。因此,进行了体内分析,以评估wisp1预处理的软骨细胞(WCS)与未经处理的软骨细胞(UCS)在颅骨缺损模型中的影响,并与未经处理的由缺陷相关血凝块(BC)或空胶原支架(CS)植入物组成的对照组进行比较。活体CT和微CT显示,UCS植入的关键缺陷矿化量较高,WCS的结构有所改善。组织学分析显示,WCS组合成代谢骨形成较高,WCS组和UCS组可见骨小梁。植入严重颅骨缺损的软骨细胞加速了原生样骨组织的形成,尤其是在培养中启动WISP1后。最终,这些数据支持使用自体软骨细胞修复颌面部严重缺陷。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Tissue Engineering
Journal of Tissue Engineering Engineering-Biomedical Engineering
CiteScore
11.60
自引率
4.90%
发文量
52
审稿时长
12 weeks
期刊介绍: The Journal of Tissue Engineering (JTE) is a peer-reviewed, open-access journal dedicated to scientific research in the field of tissue engineering and its clinical applications. Our journal encompasses a wide range of interests, from the fundamental aspects of stem cells and progenitor cells, including their expansion to viable numbers, to an in-depth understanding of their differentiation processes. Join us in exploring the latest advancements in tissue engineering and its clinical translation.
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