Early detection and treatment of wear particle-induced inflammation and bone loss in a mouse calvarial osteolysis model using HPMA copolymer conjugates.
Early detection and treatment of wear particle-induced inflammation and bone loss in a mouse calvarial osteolysis model using HPMA copolymer conjugates.
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DOI：
10.1021/mp2000555
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发表时间：
2011-08-01
影响因子：
4.9
通讯作者：
Wang D
中科院分区：
文献类型：
--
作者：
Ren K;Purdue PE;Burton L;Quan LD;Fehringer EV;Thiele GM;Goldring SR;Wang D
磨损颗粒引起的炎症被认为是全关节置换术后无菌假体松动和临床失败的主要原因。由于经常没有症状，在种植体失败之前的早期检测和干预提出了重大挑战。为了解决这一问题，我们开发了一种基于N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物的光学成像造影剂（P-IRDye），并在小鼠颅骨骨溶解模型中用于检测磨损颗粒引起的炎症。尸检后采用H&E、抗酒石酸酸性磷酸酶（TRAP）染色及μ-CT评价颗粒性颅骨骨溶解情况。粒子植入后1天，P-IRDye通过尾静脉注射给药。植入后6天动物的实时成像显示大分子造影剂在颗粒植入部位的优先分布和持续保留。胼胝体相关软组织的免疫组织化学染色和FACS分析显示F4/80、Ly-6G （Gr1）和CD11c阳性细胞广泛摄取HPMA共聚物，这是大分子探针保留在炎症部位的原因。为了测试该系统在治疗干预方面的潜力，制备了一种酸不稳定的HPMA共聚物-地塞米松缀合物（P-Dex），并在颅骨骨溶解模型中证明了它可以预防颗粒诱导的炎症和骨损伤。
Wear particle-induced inflammation is considered to be the major cause of aseptic implant loosening and clinical failure after total joint replacement. Due to the frequent absence of symptoms, early detection and intervention prior to implant failure presents a significant challenge. To address this issue, a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based optical imaging contrast agent (P-IRDye) was developed and used for the detection of wear particle-induced inflammation employing a murine calvaria osteolysis model. The particle-induced osteolysis of calvaria was evaluated by H&E, tartrate-resistant acid phosphatase (TRAP) staining and μ-CT after necropsy. One-day post particles implantation, P-IRDye was administrated to the mice via tail vein injection. Live imaging of the animals 6 days after implantation revealed the preferential distribution and sustained retention of the macromolecular contrast agent at the site of particle implantation. Immunohistochemical staining and FACS analyses of the calvaria-associated soft tissue revealed extensive uptake of the HPMA copolymer by F4/80, Ly-6G (Gr1) and CD11c positive cells, which accounts for the retention of the macromolecular probes at the inflammatory sites. To test the potential of the system for therapeutic intervention, an acid-labile HPMA copolymer-dexamethasone conjugate (P-Dex) was prepared and shown to prevent the particle-induced inflammation and bone damage in the calvaria osteolysis model.
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影响因子：
8.2
作者：
Chao Zhang;Ting-ting Tang;Ke-rong Dai
通讯作者：
Ke-rong Dai
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通讯作者：
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作者：
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通讯作者：
Wang D