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On-line Access: 2021-01-11

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Bio-Design and Manufacturing  2021 Vol.4 No.2 P.203-221

http://doi.org/10.1007/s42242-020-00118-z


A novel bio-active microsphere for meniscus regeneration via inducing cell migration and chondrocyte differentiation


Author(s):  Hongyao Xu, He Huang, Xiangjie Zou, Pengcheng Xia, Warren A. L. S. Foon & Jinwen Wang

Affiliation(s):  Department of Sports Medicine and Joint Surgery, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing 210006, Jiangsu, China

Corresponding email(s):   riversh922@hotmail.com

Key Words:  Fully reduced HMGB1 (frHMGB1), Kartogenin, Alginate microsphere, Cell migration, Meniscus regeneration


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Hongyao Xu, He Huang, Xiangjie Zou, Pengcheng Xia, Warren A. L. S. Foon & Jinwen Wang . A novel bio-active microsphere for meniscus regeneration via inducing cell migration and chondrocyte differentiation[J]. Journal of Zhejiang University Science D, 2021, 4(2): 203-221.

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Abstract: 
Meniscus injury is a common disease in clinic. If it was not treated in time, it leads to osteoarthritis which brings unbearable pain and heavy economic burden to the patients. At present, meniscectomy and meniscus suture are widely used in the treatment for meniscus injury. Nevertheless, It is not ideal for poor self-healing ability of meniscus. The recruitment of endogenous stem cells is an attractive option for wounded meniscus healing. Fully reduced high-mobility group box 1 protein (HMGB1) can accelerate the regeneration of multiple tissues by endogenous stem cell activation, migration and differentiation. kartogenin (KGN) has shown to induce the chondrogenesis of the stem cells. However, no study has explored such effects of HMGB1 and KGN in wounded meniscus healing. Therefore, in order to improve the regeneration of meniscus, we intend to use a novel bioactive microsphere which was developed by combining fully reduced high mobility group box 1 (frHMGB1) and kartogenin (KGN) with alginate gel which slowly release high concentrations of HMGB1 and KGN to activate rat bone marrow stem cells (BMSCs) and promote cell proliferation. The results showed that this HMGB1–KGN microsphere released and kept high concentrations of HMGB1 and KGN in the wound area for more than 2 weeks. In vitro experimental results showed that the HMGB1–KGN microsphere can promote cell proliferation via recruiting rat bone marrow stem cells (BMSCs) and activating the BMSCs from G0 to GAlert stage as evidenced by cell migration testing and 5-bromo-2′-deoxyuridine (BrdU) incorporation assay. In vivo results indicated that this HMGB-KGN microsphere can recruit GFP-labeled BMSCs from tail vein to wounded meniscus and induce these GFP-labeled BMSCs to differentiate into chondrocytes. Our results demonstrated that the HMGB1–KGN-containing bioactive microsphere induced cell migration in vitro and recruited the cells to wound area to promote wounded rat meniscus

南医大附属南京医院徐鸿尧等|可诱导细胞迁移和软骨细胞分化的新型生物活性微球用于半月板再生修复

本研究论文聚焦半月板损伤修复这一临床上的常见病。目前对于半月板损伤后的修复,成形切除术和半月板缝合是临床上的常用方法。然而,由于半月板的自愈能力较差,尤其在广阔白区乏血管供应,当前治疗方案并不十分理想。随着组织工程和干细胞的研究发展,内源性干细胞的招募是损伤半月板愈合的一个新的选择。本研究设计了一种新的生物活性微球,通过协同发挥完全还原高迁移率族蛋白1(frHMGB1)和Kartogenin (KGN)的促进内源性干细胞的激活、迁移和分化能力,加速损伤半月板组织的再生。以往研究已显示KGN和frHMGB1在干细胞的激活、迁移和分化过程中发挥良好的促进作用。因此,为了促进半月板的再生,我们拟将frHMGB1和KGN与海藻酸凝胶结合开发一种新型生物活性微球,缓慢释放高浓度的frHMGB1和KGN,以激活BMSCs促进细胞的增殖、迁移、分化。体内外研究结果表明,该含生物活性微球的实验效果达到预期。该研究为半月板损伤的治疗提供了新的思路,具有一定的临床应用前景。

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