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Biocompatible Porous Polyester-Ether Hydrogel Scaffolds with Cross-Linker Mediated Biodegradation and Mechanical Properties for Tissue Augmentation

机译:具有交联剂介导的生物降解性和多孔性的生物相容性多孔聚酯-醚水凝胶支架。

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摘要

Porous polyester-ether hydrogel scaffolds (PEHs) were fabricated using acid chloride/alcohol chemistry and a salt templating approach. The PEHs were produced from readily available and cheap commercial reagents via the reaction of hydroxyl terminated poly(ethylene glycol) (PEG) derivatives with sebacoyl, succinyl, or trimesoyl chloride to afford ester cross-links between the PEG chains. Through variation of the acid chloride cross-linkers used in the synthesis and the incorporation of a hydrophobic modifier (poly(caprolactone) (PCL)), it was possible to tune the degradation rates and mechanical properties of the resulting hydrogels. Several of the hydrogel formulations displayed exceptional mechanical properties, remaining elastic without fracture at compressive strains of up to 80%, whilst still displaying degradation over a period of weeks to months. A subcutaneous rat model was used to study the scaffolds in vivo and revealed that the PEHs were infiltrated with well vascularised tissue within two weeks and had undergone significant degradation in 16 weeks without any signs of toxicity. Histological evaluation for immune responses revealed that the PEHs incite only a minor inflammatory response that is reduced over 16 weeks with no evidence of adverse effects.
机译:使用酰基氯/醇化学和盐模板方法制备了多孔聚酯-醚水凝胶支架(PEH)。通过羟基封端的聚(乙二醇)(PEG)衍生物与癸二酰,琥珀酰或均苯三甲酰氯的反应,由易得且便宜的商业试剂生产PEH,以在PEG链之间提供酯交联。通过改变合成中使用的酰氯交联剂和疏水改性剂(聚己内酯(PCL))的掺入,可以调节所得水凝胶的降解速率和机械性能。几种水凝胶制剂显示出优异的机械性能,在高达80%的压缩应变下保持弹性而不会断裂,同时在数周至数月的时间内仍显示出降解。使用皮下大鼠模型在体内研究支架,发现PEHs在两周内被血管化良好的组织浸润,并且在16周内发生了明显的降解,没有任何毒性迹象。免疫反应的组织学评估显示,PEHs仅引起轻微的炎症反应,在16周内减少,没有任何不良反应的迹象。

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