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

• Published in: Bio-design and manufacturing 2021-06, Vol.4 (2), p.203-221
• Main Authors: Xu, Hongyao, Huang, He, Zou, Xiangjie, Xia, Pengcheng, Foon, Warren A. L. S., Wang, Jinwen
• Format: Article
• Language: English
• Subjects: Alginic acid; Biomaterials; Biomedical Engineering and Bioengineering; Bone marrow; Cartilage; Cell activation; Cell adhesion & migration; Cell differentiation; Cell migration; Cell proliferation; Chemokines; Chondrocytes; Chondrogenesis; Engineering; HMGB1 protein; Hydrogels; Mechanical Engineering; Medical research; Mobility; Orthopedics; Prenatal development; Proteins; Regeneration; Research Article; Stem cells; Wound healing; Wounds
• ISSN: 2096-5524; 2522-8552
• DOI: 10.1007/s42242-020-00118-z

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 G 0 to G Alert 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 healing in vivo.