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In situ foamable, degradable polyurethane as biomaterial for soft tissue repair

机译:原位可发泡可降解聚氨酯作为生物材料修复软组织

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Degradable foams which can be inserted endoscopically as liquid or pasty mixtures into soft tissue defects possess a promising potential for the surgical treatment of such defects. The defects can be sealed under in situ foaming and simultaneous material expansion. We developed an in situ foamable (L-lactide-co-ε-caprolactone)-based, star-shaped prepolymer by ring opening polymerization of L-lactide and ε-caprolactone in the presence of meso-erythritol as starter. By conversion of the terminal hydroxyl groups of the formed oligoester with lysine diisocyanate ethyl ester (LDI) an isocyanate-endcapped, reactive prepolymer has been received. Foaming can be initiated by addition of l,4-diazabicyclo[2,2,2]octane (DABCO), water, LDI and DMSO. By varying the composition of these additives, the foaming and curing time could be varied within a clinically acceptable range. A porosity of approximately 90%, and an average tensile strength of 0.3 MPa with elongations of 90% were determined for the foams. In vitro cytotoxicity on cured foams was assayed on 3T3 fibroblasts and demonstrated an excellent cytocompatibility. This was also confirmed in an in vivo study using an established rat model, where prefabricated foams and in situ hardening material were inserted into subdermal skin incisions in parallel. The feature of chronic inflammation was only weakly developed in both groups and slightly more pronounced and persisted for longer time in the group of in situ foamed material. In both groups the foreign materials were vascularized, degraded and substituted by connective tissue. The results encourage to proceed with trials where the materials are used to fill more heavily loaded defects.
机译:可以内窥镜形式以液体或糊状混合物形式插入软组织缺损中的可降解泡沫在外科治疗此类缺损方面具有广阔的前景。可以在原位发泡和同时进行材料膨胀的情况下密封缺陷。我们在中-赤藓糖醇作为起始剂的情况下,通过L-丙交酯和ε-己内酯的开环聚合反应,开发了一种基于原位发泡(L-丙交酯-ε-己内酯)的星形预聚物。通过将形成的低聚酯的末端羟基与赖氨酸二异氰酸酯乙酯(LDI)转化,可以得到异氰酸酯封端的反应性预聚物。可以通过添加1,4-二氮杂双环[2,2,2]辛烷(DABCO),水,LDI和DMSO引发发泡。通过改变这些添加剂的组成,发泡和固化时间可以在临床上可接受的范围内变化。测得泡沫的孔隙率约为90%,平均拉伸强度为0.3 MPa,伸长率为90%。在3T3成纤维细胞上测定了对固化泡沫的体外细胞毒性,并证明了优异的细胞相容性。使用已建立的大鼠模型进行的一项体内研究也证实了这一点,其中将预制泡沫和原位硬化材料平行插入皮下皮肤切口。慢性炎症的特征仅在两组中较弱地发展,并且在原位发泡材料组中稍显着并且持续更长的时间。在两组中,异物均被血管化,降解并被结缔组织替代。结果鼓励继续进行试验,在试验中使用材料填充更重的缺陷。

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