Abstract:
: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 SIGNIFICANCE: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 has an inhibitory effect on necrotic cell death, particularly caspase-1-mediated necrotic cell death (pyroptosis). In in vivo study, it showed higher healing rate of the damaged cartilage in a 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.
journal_name
Acta Biomaterjournal_title
Acta biomaterialiaauthors
Park KS,Kim BJ,Lih E,Park W,Lee SH,Joung YK,Han DKdoi
10.1016/j.actbio.2018.04.022subject
Has Abstractpub_date
2018-06-01 00:00:00pages
204-216eissn
1742-7061issn
1878-7568pii
S1742-7061(18)30225-3journal_volume
73pub_type
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journal_title:Acta biomaterialia
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journal_title:Acta biomaterialia
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journal_title:Acta biomaterialia
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pub_type: 杂志文章
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更新日期:2017-09-15 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
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journal_title:Acta biomaterialia
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更新日期:2018-07-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
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更新日期:2008-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:2016-09-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2012.07.035
更新日期:2012-12-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
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journal_title:Acta biomaterialia
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journal_title:Acta biomaterialia
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journal_title:Acta biomaterialia
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更新日期:2012-09-01 00:00:00
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