State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China.
Acta Biomater. 2017 Jun;55:396-409. doi: 10.1016/j.actbio.2017.03.042. Epub 2017 Mar 29.
In vivo behavior of hydrogel-based biomaterials is very important for rational design of hydrogels for various biomedical applications. Herein, we developed a facile method for in situ fabrication of radiopaque hydrogel. An iodinated functional diblock copolymer of poly(ethylene glycol) and aliphatic polyester was first synthesized by coupling the hydroxyl end of the diblock copolymer with 2,3,5-triiodobenzoic acid (TIB) and then a radiopaque thermoreversible hydrogel was obtained by mixing it with the virgin diblock copolymer. A concentrated aqueous solution of the copolymer blend was injectable at room temperature and spontaneously turned into an in situ hydrogel at body temperature after injection. The introduction of TIB moieties affords the capacity of X-ray opacity, enabling in vivo visualization of the hydrogel using Micro-CT. A rat model with cecum and abdominal defects was utilized to evaluate the efficacy of the radiopaque hydrogel in the prevention of post-operative adhesions, and a significant reduction of the post-operative adhesion formation was confirmed. Meanwhile, the maintenance of the radiopaque hydrogel in the abdomen after administration was non-destructively detected via Micro-CT scanning. The reconstructed three-dimensional images showed that the radiopaque hydrogel with an irregular morphology was located on the injured abdominal wall. The time-dependent profile of the volume of the radiopaque hydrogel determined by Micro-CT imaging was well consistent with the trend obtained from the dissection observation. Therefore, the radiopaque thermoreversible hydrogel can serve as a potential visualized biomedical implant and this practical mixing approach is also useful for further extension into the in vivo monitoring of other biomaterials.
While a variety of biomaterials have been extensively studied, it is rare to monitor in vivo degradation and medical efficacy of a material after being implanted deeply into the body. Herein, the radiopaque thermoreversible hydrogel developed by us not only holds desirable performance on the prevention of post-operative abdominal adhesions, but also allows non-invasive monitoring of its in vivo degradation with CT imaging in a real-time, quantitative and three-dimensional manner. The methodology based on CT imaging provides important insights into the in vivo fate of the hydrogel after being deeply implanted into mammals for different biomedical applications and significantly reduces the amount of animals sacrificed.
水凝胶基生物材料的体内行为对于各种生物医学应用中水凝胶的合理设计非常重要。在此,我们开发了一种简便的方法来原位制备放射线可透的水凝胶。首先,通过将二嵌段共聚物的羟基端与 2,3,5-三碘苯甲酸(TIB)偶联,合成了一种碘代功能二嵌段共聚物的聚(乙二醇)和脂肪族聚酯,然后将其与原始二嵌段共聚物混合,得到一种放射线可透的温敏可逆水凝胶。共聚物混合物的浓水溶液在室温下可注射,注射后在体温下自发转变为原位水凝胶。TIB 部分的引入赋予了 X 射线不透明度,使水凝胶能够使用 Micro-CT 进行体内可视化。利用盲肠和腹部缺损的大鼠模型评估放射线可透水凝胶在预防术后粘连中的功效,证实了术后粘连形成的显著减少。同时,通过 Micro-CT 扫描对给药后腹部放射线可透水凝胶的保留情况进行了非破坏性检测。重建的三维图像显示,形态不规则的放射线可透水凝胶位于受伤的腹壁上。通过 Micro-CT 成像确定的放射线可透水凝胶体积的时变曲线与从解剖观察获得的趋势非常吻合。因此,放射线可透温敏可逆水凝胶可用作潜在的可视化生物医学植入物,这种实用的混合方法也可用于进一步扩展对其他生物材料的体内监测。
虽然已经广泛研究了各种生物材料,但很少有研究监测材料被植入体内深处后的体内降解和医疗效果。在此,我们开发的放射线可透温敏可逆水凝胶不仅在预防术后腹部粘连方面表现出良好的性能,而且还可以通过 CT 成像以实时、定量和三维的方式对其体内降解进行非侵入性监测。基于 CT 成像的方法为深入了解水凝胶在不同生物医学应用中被深度植入哺乳动物体内后的体内命运提供了重要的见解,并显著减少了实验动物的数量。