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

• Published in: Acta biomaterialia 2018-06, Vol.73, p.204-216
• Main Authors: Park, Kwang-Sook, Kim, Byoung-Ju, Lih, Eugene, Park, Wooram, Lee, Soo-Hong, Joung, Yoon Ki, Han, Dong Keun
• Format: Article
• Language: English
• Subjects: Acidification; Apoptosis; Biocompatibility; Biodegradability; Biodegradation; Biomedical materials; Bone marrow; Calcification; Cartilage; Caspase; Caspase-1; Cell death; Chondrogenesis; Chondrogenesis - drug effects; Cytokines; Degradation; Degradation products; Differentiation; Glycolic acid; Healing; Humans; In vivo methods and tests; Inflammation; Interleukin 1; Magnesium; Magnesium hydroxide; Magnesium Hydroxide - chemistry; Magnesium Hydroxide - pharmacology; Mechanical properties; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchyme; Mortality; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Neutralization; Patients; pH effects; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Polylactic Acid-Polyglycolic Acid Copolymer - pharmacology; Polylactide-co-glycolide; Polymers; Pyroptosis; Regeneration; Scaffolds; Stem cell transplantation; Stem cells; Tissue engineering; Tissue Scaffolds - chemistry
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2018.04.022

[Display omitted] 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. Synthetic polymer scaffolds have been widely utilized for tissue regeneration. However, they have a disadvantage of releasing acidic products through degradation. This paper demonstrated a novel type of synthetic polymer scaffold with pH-neutralizing ceramic nanoparticles composed of magnesium hydroxide for cartilage regeneration. This polymer showed pH-neutralization property 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