Versatile effects of magnesium hydroxide nanoparticles in PLGA scaffold–mediated chondrogenesis

Publication date: Available online 16 April 2018
Source:Acta Biomaterialia
Author(s): Kwang-Sook Park, Byoung-Ju Kim, Eugene Lih, Wooram Park, Soo-Hong Lee, Yoon Ki Joung, Dong Keun Han
Artificial scaffolds made up of various synthetic biodegradable polymers have been reported to have many advantages including cheap manufacturing, easy scale up, high mechanical strength, convenient manipulation, and molding into an unlimited variety of shapes. However, the synthetic biodegradable polymers still have the insufficiency for cartilage regeneration owing to their acidic degradation products. To reduce acidification by degradation of synthetic polymers, we incorporated magnesium hydroxide (MH) nanoparticles into porous polymer scaffold not only to effectively neutralize the acidic hydrolysate but also to minimize the structural disturbance of scaffolds. The neutralization effect of poly(D,L-lactic-co-glycolic acid; PLGA)/MH scaffold was confirmed with the maintenance of neutral pH, contrary to a PLGA scaffold with low pH. Further, the scaffolds were applied to evaluate the chondrogenic differentiation of the human bone marrow mesenchymal stem cells. In in vitro study, the PLGA/MH scaffold enhanced the chondrogenesis markers and reduced the calcification, compared to the PLGA scaffold. Additionally, the PLGA/MH scaffold reduced the release of inflammatory cytokines, compared to the PLGA scaffold, as the cell death decreased. Moreover, the addition of MH reduced necrotic cell death at the early stage of chondrogenic differentiation. Further, the necrotic cell death by the PLGA scaffold was mediated by cleavage of caspase-1, the so-called interleukin 1-converting enzyme, and MH alleviated it as well as nuclear factor kappa B expression. Furthermore, the PLGA/MH scaffold highly supported chondrogenic healing of rat osteochondral defect sites in in vivo study. Therefore, it was suggested that a synthetic polymer scaffold containing MH could be a novel healing tool to support cartilage regeneration and further treatment of orthopedic patients.Statement of SignificanceSynthetic polymer scaffolds have been widely utilized for tissue regeneration. However, they have limitations of acidic products by degradation. This paper demonstrated a novel type of synthetic polymer scaffold with pH-neutralizing ceramic nanoparticles, magnesium hydroxide, for cartilage regeneration. It showed pH-neutralization during polymer degradation and significant enhancement of chondrogenic differentiation of mesenchymal stem cells. It reduced not only chondrogenic calcification but also release of proinflammatory cytokines. Moreover, it has an inhibitive effect on necrotic cell death, particularly caspase-1-mediated necrotic cell death (pyroptosis). In in vivo study, it showed higher healing of damaged cartilage in rat osteochondral defect model. We expected that this novel type of scaffold can be effectively applied to support cartilage regeneration and further treatment of orthopedic patients.

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