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3D 打印生物功能化支架修复软骨缺损的微骨折。

3D printed biofunctionalized scaffolds for microfracture repair of cartilage defects.

机构信息

Fischell Department of Bioengineering, University of Maryland, College Park, MD USA; Center for Engineering Complex Tissues, University of Maryland, College Park, MD USA.

Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD USA.

出版信息

Biomaterials. 2018 Dec;185:219-231. doi: 10.1016/j.biomaterials.2018.09.022. Epub 2018 Sep 14.

Abstract

While articular cartilage defects affect millions of people worldwide from adolescents to adults, the repair of articular cartilage defects still remains challenging due to the limited endogenous regeneration of the tissue and poor integration with implants. In this study, we developed a 3D-printed scaffold functionalized with aggrecan that supports the cellular fraction of bone marrow released from microfracture, a widely used clinical procedure, and demonstrated tremendous improvement of regenerated cartilage tissue quality and joint function in a lapine model. Optical coherence tomography (OCT) revealed doubled thickness of the regenerated cartilage tissue in the group treated with our aggrecan functionalized scaffold compared to standard microfracture treatment. H&E staining showed 366 ± 95 chondrocytes present in the unit area of cartilage layer with the support of bioactive scaffold, while conventional microfracture group showed only 112 ± 26 chondrocytes. The expression of type II collagen appeared almost 10 times higher with our approach compared to normal microfracture, indicating the potential to overcome the fibro-cartilage formation associated with the current microfracture approach. The therapeutic effect was also evaluated at joint function level. The mobility was evaluated using a modified Basso, Beattie and Bresnahan (BBB) scale. While the defect control group showed no movement improvement over the course of study, all experimental groups showed a trend of increasing scores over time. The present work developed an effective method to regenerate critical articular defects by combining a 3D-printed therapeutic scaffold with the microfracture surgical procedure. This biofunctionalized acellular scaffold has great potential to be applied as a supplement for traditional microfracture to improve the quality of cartilage regeneration in a cost and labor effective way.

摘要

虽然关节软骨缺损影响着全球数以百万计的青少年和成年人,但由于组织的内源性再生有限以及与植入物的整合不良,关节软骨缺损的修复仍然具有挑战性。在这项研究中,我们开发了一种 3D 打印支架,其表面功能化有聚集蛋白聚糖,可支持微骨折(一种广泛应用的临床手术)释放的骨髓细胞,在兔模型中,我们展示了这种支架在再生软骨组织质量和关节功能方面的巨大改善。光学相干断层扫描(OCT)显示,与标准微骨折治疗相比,用我们的聚集蛋白聚糖功能化支架治疗的组的再生软骨组织厚度增加了一倍。H&E 染色显示,在生物活性支架的支持下,每个软骨层单位面积有 366±95 个软骨细胞,而传统微骨折组仅显示 112±26 个软骨细胞。与正常微骨折相比,我们的方法使 II 型胶原的表达增加了近 10 倍,表明有可能克服与当前微骨折方法相关的纤维软骨形成。还在关节功能水平上评估了治疗效果。采用改良的 Basso、Beattie 和 Bresnahan(BBB)量表评估活动度。虽然缺陷对照组在研究过程中没有改善活动度,但所有实验组的评分均随着时间的推移呈上升趋势。本工作通过将 3D 打印治疗支架与微骨折手术相结合,开发了一种有效再生关键关节缺损的方法。这种无细胞生物功能化支架具有很大的潜力,可作为传统微骨折的补充,以具有成本效益和劳动效益的方式提高软骨再生的质量。

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