Sustained inhibition of CC-chemokine receptor-2 via intraarticular deposition of polymeric microplates in post-traumatic osteoarthritis.
Sustained inhibition of CC-chemokine receptor-2 via intraarticular deposition of polymeric microplates in post-traumatic osteoarthritis.
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DOI：
10.1007/s13346-022-01235-1
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发表时间：
2023-02
影响因子：
5.4
通讯作者：
Longobardi, Lara
中科院分区：
文献类型：
--
作者：
Ozkan, Huseyin;Di Francesco, Martina;Willcockson, Helen;Valdes-Fernandez, Jose;Di Francesco, Valentina;Granero-Molto, Froilan;Prosper, Felipe;Decuzzi, Paolo;Longobardi, Lara
创伤后骨关节炎（PTOA）主要通过皮质类固醇治疗，在严重的情况下，全关节置换术仍然是唯一有效的干预措施。为了评估CCR2靶向治疗pta的治疗潜力，我们使用可生物降解微孔板（µPLs）实现CCR2抑制剂RS504393在损伤膝关节内缓慢持续的关节内释放，并跟踪疾病进展期间的关节损伤。负载rs504393的µPLs （RS-µPLs）通过模板复制成型技术制备。在聚乙烯醇（PVA）方形模板中，将聚乳酸-羟基乙酸（PLGA）和RS504393的混合物沉积在20 × 10 μm（长×高）的孔中。经过理化和毒理学表征后，在PBS缓冲液中评估µPL中RS504393的释放谱。C57BL/6 J雄性小鼠进行内侧半月板失稳(DMM)/假手术，术后1周关节内给予RS-µPLs （1 mg/kg）。dmm后4周和7周重复给药。无药µPLs （DF-µPLs）和生理盐水注射作为对照。小鼠分别在dmm后4周和10周实施安乐死，分别对应于早期和严重的PTOA阶段。评估膝关节软骨结构评分（ACS、H&E）、基质损失（红花素O评分）、软骨到骨的骨赘形成和成熟（软骨量化）、软骨下板厚度。RS-µPL结构确保了CCR2抑制剂在数周内的持续释放，在21天内仍有20%的RS504393抑制剂可用。这种延长的释放改善了软骨结构，减少了两个阶段的骨损伤和滑膜增生。细胞外基质损失也有所减轻，但效果较差。结果表明，优化ccr2靶向治疗需要局部持续递送。在线版本包含补充材料，可在10.1007/s13346-022-01235-1获得。
Posttraumatic osteoarthritis (PTOA) is mostly treated via corticosteroid administration, and total joint arthroplasty continues to be the sole effective intervention in severe conditions. To assess the therapeutic potential of CCR2 targeting in PTOA, we used biodegradable microplates (µPLs) to achieve a slow and sustained intraarticular release of the CCR2 inhibitor RS504393 into injured knees and followed joint damage during disease progression. RS504393-loaded µPLs (RS-µPLs) were fabricated via a template-replica molding technique. A mixture of poly(lactic-co-glycolic acid) (PLGA) and RS504393 was deposited into 20 × 10 μm (length × height) wells in a polyvinyl alcohol (PVA) square-patterned template. After physicochemical and toxicological characterizations, the RS504393 release profile from µPL was assessed in PBS buffer. C57BL/6 J male mice were subjected to destabilization of the medial meniscus (DMM)/sham surgery, and RS-µPLs (1 mg/kg) were administered intraarticularly 1 week postsurgery. Administrations were repeated at 4 and 7 weeks post-DMM. Drug free-µPLs (DF-µPLs) and saline injections were performed as controls. Mice were euthanized at 4 and 10 weeks post-DMM, corresponding to the early and severe PTOA stages, respectively. Knees were evaluated for cartilage structure score (ACS, H&E), matrix loss (safranin O score), osteophyte formation and maturation from cartilage to bone (cartilage quantification), and subchondral plate thickness. The RS-µPL architecture ensured the sustained release of CCR2 inhibitors over several weeks, with ~ 20% of RS504393 still available at 21 days. This prolonged release improved cartilage structure and reduced bone damage and synovial hyperplasia at both PTOA stages. Extracellular matrix loss was also attenuated, although with less efficacy. The results indicate that local sustained delivery is needed to optimize CCR2-targeted therapies. The online version contains supplementary material available at 10.1007/s13346-022-01235-1.
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用于关节内持续释放地塞米松治疗超负荷引起的骨关节炎的形状限定微板。
影响因子：
9.5
作者：
Di Francesco M;Bedingfield SK;Di Francesco V;Colazo JM;Yu F;Ceseracciu L;Bellotti E;Di Mascolo D;Ferreira M;Himmel LE;Duvall C;Decuzzi P
通讯作者：
Decuzzi P
影响因子：
13.3
作者：
Jackson, Miriam T.;Moradi, Babak;Little, Christopher B.
通讯作者：
Little, Christopher B.
DOI：
10.1016/s2665-9913(21)00116-8
发表时间：
2021-09
期刊：
The Lancet. Rheumatology
影响因子：
--
作者：
Garriga C;Goff M;Paterson E;Hrusecka R;Hamid B;Alderson J;Leyland K;Honeyfield L;Greenshields L;Satchithananda K;Lim A;Arden NK;Judge A;Williams A;Vincent TL;Watt FE
通讯作者：
Watt FE
影响因子：
13.3
作者：
Appleton, C. Thomas G.;Usmani, Shirine E.;Beier, Frank
通讯作者：
Beier, Frank
影响因子：
5.4
作者：
Moore, Thomas L.;Cook, Alexander B.;Belotti, Elena;Palomba, Roberto;Manghnani, Purnima;Spano, Raffaele;Brahmachari, Sayanti;Di Francesco, Martina;Palange, Anna Lisa;Di Mascolo, Daniele;Decuzzi, Paolo
通讯作者：
Decuzzi, Paolo