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ε-聚赖氨酸(EPL)涂层纳米级聚己内酯/羟基磷灰石支架在兔颅骨骨缺损中的免疫反应和骨缺损修复功能。

The immunogenic reaction and bone defect repair function of ε-poly-L-lysine (EPL)-coated nanoscale PCL/HA scaffold in rabbit calvarial bone defect.

机构信息

Department of Prosthodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.

Liangxiang Hospital of Beijing Fangshan District, Beijing, China.

出版信息

J Mater Sci Mater Med. 2021 Jun 7;32(6):63. doi: 10.1007/s10856-021-06533-7.

Abstract

Tissue engineering is a promising strategy for bone tissue defect reconstruction. Immunogenic reaction, which was induced by scaffolds degradation or contaminating microorganism, influence cellular activity, compromise the efficiency of tissue engineering, or eventually lead to the failure of regeneration. Inhibiting excessive immune response through modulating scaffold is critical important to promote tissue regeneration. Our previous study showed that ε-poly-L-lysine (EPL)-coated nanoscale polycaprolactone/hydroxyapatite (EPL/PCL/HA) composite scaffold has enhanced antibacterial and osteogenic properties in vitro. However, the bone defect repair function and immunogenic reaction of EPL/PCL/HA scaffolds in vivo remains unclear. In the present study, three nanoscale scaffolds (EPL/PCL/HA, PCL and PCL/HA) were transplanted into rabbit paraspinal muscle pouches, and T helper type 1 (Th1), T helper type 2 (Th2), T helper type 17 (Th17), and macrophage infiltration were analyzed after 1 week and 2 weeks to detect their immunogenic reaction. Then, the different scaffolds were transplanted into rabbit calvarial bone defect to compare the bone defect repair capacities. The results showed that EPL/PCL/HA composite scaffolds decreased pro-inflammatory Th1, Th17, and type I macrophage infiltration from 1 to 2 weeks, and increased anti-inflammatory Th2 infiltration into the regenerated area at 2 weeks in vivo, when compared to PCL and PCL/HA. In addition, EPL/PCL/HA showed an enhanced bone repair capacity compared to PCL and PCL/HA when transplanted into rabbit calvarial bone defects at both 4 and 8 weeks. Hence, our results suggest that EPL could regulate the immunogenic reaction and promote bone defect repair function of PCL/HA, which is a promising agent for tissue engineering scaffold modulation.

摘要

组织工程是一种有前途的骨组织缺损重建策略。免疫原性反应,由支架降解或污染的微生物引起,影响细胞活性,降低组织工程的效率,或最终导致再生失败。通过调节支架抑制过度的免疫反应对于促进组织再生至关重要。我们之前的研究表明,ε-聚-L-赖氨酸(EPL)涂层纳米聚己内酯/羟基磷灰石(EPL/PCL/HA)复合支架在体外具有增强的抗菌和成骨性能。然而,EPL/PCL/HA 支架在体内的骨缺损修复功能和免疫原性反应尚不清楚。在本研究中,三种纳米支架(EPL/PCL/HA、PCL 和 PCL/HA)被移植到兔椎旁肌肉囊中,在 1 周和 2 周后分析 T 辅助细胞 1(Th1)、T 辅助细胞 2(Th2)、T 辅助细胞 17(Th17)和巨噬细胞浸润,以检测其免疫原性反应。然后,将不同的支架移植到兔颅骨骨缺损中,以比较骨缺损修复能力。结果表明,与 PCL 和 PCL/HA 相比,EPL/PCL/HA 复合支架在体内第 1 周到第 2 周降低了促炎 Th1、Th17 和 I 型巨噬细胞浸润,第 2 周增加了抗炎 Th2 向再生区的浸润。此外,与 PCL 和 PCL/HA 相比,EPL/PCL/HA 移植到兔颅骨骨缺损中在第 4 周和第 8 周均表现出增强的骨修复能力。因此,我们的结果表明,EPL 可以调节免疫原性反应并促进 PCL/HA 的骨缺损修复功能,这是一种有前途的组织工程支架调节剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e175/8184523/ec89412af785/10856_2021_6533_Fig1_HTML.jpg

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