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首页> 外文期刊>Materials science & engineering >Dexamethasone-loaded, injectable pullulan-poly(ethylene glycol) hydrogels for bone tissue regeneration in chronic inflammatory conditions
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Dexamethasone-loaded, injectable pullulan-poly(ethylene glycol) hydrogels for bone tissue regeneration in chronic inflammatory conditions

机译：用于慢性炎症条件下的骨组织再生的地塞米松装载，可注射的胰蛋白酶（乙二醇）水凝胶

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Chronic inflammation, infection, and fixation stability disrupts bone tissue regeneration by implants. The elevated levels of inflammatory markers and reactive oxygen species (ROS) damage tissues, inhibit osteoblastic differentiation, and promote bone resorption. Activation of local and chronic inflammatory responses due to the implantable biomaterial poses a high risk of implant failure and compromised bone repair in several pathological conditions. Not much progress has been made in the development of biomaterials that can counter inflammation and ROS along with inducing osteogenic activities for managing bone defects/injuries. We have developed, for the first time, injectable polymeric hydrogels by crosslinking oxidized pullulan (OP, 1% w/v) and 8-arm PEG hydrazine (PEG-HY, 10% w/v) using pH-sensitive and dynamic hydrazone linkages at 37 degrees C in buffer. The hydrogels were loaded with dexamethasone (Dex), an anti-inflammatory corticosteroid and osteogenic inducer, by covalently linking it to PEG-HY by hydrazone linkages, and their morphological, injectability, viscoelastic, self-healing, swelling, and drug-release properties were investigated. The hydrogels provided a pH-sensitive sustained release of PEG-Dex conjugate (3.62 wt%, 9.22 x 10-5 mol of Dex/gram) for 28 days, with 74.54 and 55.15% PEG-Dex conjugate being released at pH 6.5 and 7.4. ABTS assay showed that hydrogels inhibited 68% radicals within 1 h, and treatment with hydrogel releasates inhibited the pro-inflammatory markers, IL-6 and IL-18, and elevated the anti-inflammatory marker, TGF-8, in murine osteoblast precursor cells (MC3T3E1). The hydrogels were found suitable for cell encapsulation and they exhibited 110% viability on treatment with releasates. Finally, the osteogenic activities of hydrogels were ascertained by alkaline phosphatase (ALP) activities, alizarin red S staining, and osteogenic gene expressions- RUNX2, Col-I, OPN, and IBSP. Overall, PEGDex conjugate released from hydrogels improved the cell viability and proliferation, and induced the osteoblastic differentiation. The hydrogels with their promising antioxidant and anti-inflammatory properties along with the osteogenic activities show a strong potential as an injectable, extracellular matrix (ECM)-mimicking implantable drug-depot for bone repair applications in chronic inflammatory conditions.
机译：慢性炎症，感染和固定稳定性破坏植入物的骨组织再生。炎症标志物和反应性氧物质（ROS）损伤组织的升高，抑制骨细胞分化，促进骨吸收。由于可植入的生物材料引起的局部和慢性炎症反应的激活具有高风险的植入物衰竭并且在几种病理条件下受损骨修复。在可以对抗炎症和RO的生物材料的发展中取得了不多进展，以及诱导骨缺损/伤害的成骨活性。我们通过使用pH敏感和动态的腙键交联通过交联通过交联氧化的支链（OP，1％W / V）和8臂PEG肼（PEG-HY，10％W / V）来开发可注射的聚合物水凝胶在37摄氏度中的缓冲区。通过通过腙键共价将其与PEG-Hy共价连接到抗炎皮质类固醇和成骨诱导剂的水凝胶加载到抗炎皮质类固醇和成骨诱导症上，以及它们的形态学，可注射性，粘弹性，自我愈合，肿胀和药物释放性能被调查了。水凝胶提供了PEG-DEX缀合物（3.62wt％，9.22×10-5mol的DEX /克）的pH敏感的持续释放28天，74.54和55.15％PH 6.5和7.4释放的PEG-DEX缀合物。 ABTS测定表明，水凝胶在1小时内抑制了68％的基团，并且用水凝胶的处理释放抑制促炎标记物，IL-6和IL-18，并升高了鼠骨细胞前体细胞中的抗炎标志物TGF-8 （MC3T3E1）。发现水凝胶适用于细胞包封，并且它们在释放时表现出110％的活力。最后，通过碱性磷酸酶（ALP），茜素红S染色和成骨基因表达 - RONX2，COL-I，OPN和IBSP来确定水凝胶的成骨活性。总体而言，从水凝胶中释放的PEGDEX缀合物改善了细胞活力和增殖，并诱导了骨细胞分化。水凝胶具有有前途的抗氧化剂和抗炎性能以及骨质发生的活性，表现为可注射的细胞外基质（ECM）的强势，用于慢性炎症条件下的骨修复应用的可植入药物仓库。

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