Releasing Behavior of Lipopolysaccharide from Gelatin Modulates Inflammation, Cellular Senescence, and Bone Formation in Critical-Sized Bone Defects in Rat Calvaria
Releasing Behavior of Lipopolysaccharide from Gelatin Modulates Inflammation, Cellular Senescence, and Bone Formation in Critical-Sized Bone Defects in Rat Calvaria
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DOI：
10.3390/ma13010095
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发表时间：
2019-12
期刊：
影响因子：
3.4
通讯作者：
Jianxin Zhao;Y. Honda;Tomonari Tanaka;Y. Hashimoto;N. Matsumoto
中科院分区：
文献类型：
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作者：
Jianxin Zhao;Y. Honda;Tomonari Tanaka;Y. Hashimoto;N. Matsumoto
脂多糖（LPS）是众所周知的强炎症诱导剂。然而，关于脂多糖释放行为如何影响受影响区域的细胞衰老的信息很少。在本文中，我们证明可以利用真空加热技术（脱水热处理）来制备LPS缓释明胶海绵（LS-G）。明胶中脂多糖的持续释放导致大鼠颅骨临界大小的骨缺损中衰老细胞长期存在。本研究制备了三种类型的明胶海绵：LPS 含量极低的医用级明胶海绵 (MG)、LS-G 和 LPS 快速释放明胶海绵 (LR-G)。组织学 (H-E) 和免疫组织化学 (COX-2、p16 和 p21) 染色用于评估术后一到三周的炎症反应和细胞衰老。利用软 X 射线成像来估计缺损处新骨的形成。与 MG 和 LS-G 相比，1 周时 LR-G 导致缺损处出现更强的肿胀和 COX-2 表达。尽管炎症反应较小，但与 MG 和 LR-G 相比，LS-G 植入导致衰老细胞长期存在并阻碍骨形成。这些结果表明真空加热是制备不同类型材料以释放细菌成分的可行技术，这有助于开发阐明细胞衰老和骨再生的疾病模型。
Lipopolysaccharide (LPS) is a well-known strong inducer of inflammation. However, there is little information regarding how LPS-release behavior affects cellular senescence at the affected area. In this paper, we demonstrate that a vacuum-heating technique (dehydrothermal treatment) can be utilized to prepare an LPS sustained-release gelatin sponge (LS-G). LPS sustained release from gelatin leads to the long-term existence of senescent cells in critical-sized bone defects in rat calvaria. Three types of gelatin sponges were prepared in this study: a medical-grade gelatin sponge with extremely low LPS levels (MG), LS-G, and a LPS rapid-release gelatin sponge (LR-G). Histological (H-E) and immunohistochemical (COX-2, p16, and p21) staining were utilized to evaluate inflammatory reactions and cellular senescence one to three weeks after surgery. Soft X-ray imaging was utilized to estimate new bone formation in the defects. The LR-G led to stronger swelling and COX-2 expression in defects compared to the MG and LS-G at 1 week. Despite a small inflammatory reaction, LS-G implantation led to the long-term existence of senescent cells and hampered bone formation compared to the MG and LR-G. These results suggest that vacuum heating is a viable technique for preparing different types of materials for releasing bacterial components, which is helpful for developing disease models for elucidating cellular senescence and bone regeneration.