Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea.
Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi 13488, Republic of Korea.
Acta Biomater. 2018 Jun;73:204-216. doi: 10.1016/j.actbio.2018.04.022. Epub 2018 Apr 16.
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 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.
各种合成可生物降解聚合物制成的人工支架具有许多优点，包括制造便宜、易于规模化、机械强度高、操作方便以及可模制成各种形状。然而，由于其酸性降解产物，合成可生物降解聚合物在软骨再生方面仍存在不足。为了减少合成聚合物降解引起的酸化，我们将纳米级氢氧化镁（MH）掺入多孔聚合物支架中，不仅可以有效中和酸性水解产物，还可以最大限度地减少支架的结构干扰。聚（D，L-乳酸-共-乙醇酸；PLGA）/MH 支架的中和效果通过维持中性 pH 得到证实，而 PLGA 支架的 pH 值较低。此外，该支架还用于评估人骨髓间充质干细胞的软骨分化。在体外研究中，与 PLGA 支架相比，PLGA/MH 支架增强了软骨形成标志物并减少了钙化。此外，与 PLGA 支架相比，PLGA/MH 支架减少了炎症细胞因子的释放，细胞死亡减少。此外，MH 的添加减少了软骨形成分化早期的坏死细胞死亡。此外，PLGA 支架介导的坏死细胞死亡是通过半胱天冬酶-1（即白细胞介素 1 转化酶）的切割，MH 减轻了这种情况以及核因子 kappa B 的表达。此外，在体内研究中，PLGA/MH 支架高度支持大鼠骨软骨缺损部位的软骨愈合。因此，我们认为含有 MH 的合成聚合物支架可能是一种新型的愈合工具，可以支持软骨再生和进一步治疗骨科患者。
合成聚合物支架已广泛用于组织再生。然而，它们有一个缺点，即通过降解释放酸性产物。本文介绍了一种新型的合成聚合物支架，该支架由氢氧化镁组成，具有 pH 中和陶瓷纳米粒子，用于软骨再生。这种聚合物在聚合物降解过程中表现出 pH 中和特性，并显著增强间充质干细胞的软骨分化。它不仅减少了软骨形成的钙化，而且减少了促炎细胞因子的释放。此外，它对坏死细胞死亡具有抑制作用，特别是半胱天冬酶-1 介导的坏死细胞死亡（细胞焦亡）。在体内研究中，它在大鼠骨软骨缺损模型中显示出更高的受损软骨愈合率。我们期望这种新型支架能够有效地应用于支持软骨再生和进一步治疗骨科患者。
