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Engineering highly swellable dual-responsive protein-based injectable hydrogels: the effects of molecular structure and composition in vivo
Biomaterials Science ( IF 6.6 ) Pub Date : 2017-09-21 00:00:00 , DOI: 10.1039/c7bm00707h
V. H. Giang Phan 1, 2, 3, 4, 5 , Thavasyappan Thambi 1, 2, 3, 4, 5 , Bong Sup Kim 1, 2, 3, 4, 5 , Dai Phu Huynh 6, 7, 8, 9, 10 , Doo Sung Lee 1, 2, 3, 4, 5
Affiliation  

Stimuli-responsive hydrogels, known as smart hydrogels, are three-dimensional amphiphilic or hydrophilic polymer networks that are able to change their volume or phase, and other properties, including viscosity, structure, and dimension, in response to changes in pH, temperature, and magnetic or electric field. Highly swellable, dual-responsive bovine serum albumin (BSA)-based injectable hydrogels are prepared here by the chemical conjugation of pH- and temperature-responsive oligo(sulfamethazine acrylate-co-N-isopropylacrylamide) (oligo(SMA-co-NIPAM)) copolymers on the surface of BSA through carbodiimide-mediated chemistry. The pH- and temperature-responsive oligomer-bearing BSA conjugates show rapid sol-to-gel phase transition properties. Specifically, the free-flowing conjugates at high pH (pH 8.4, 23 °C) are transformed to a viscoelastic gel under physiological conditions (pH 7.4, 37 °C). The swelling ratio, gel strength, and pore size of the BSA hydrogel were tuned by altering the conjugation ratio of the oligo(SMA-co-NIPAM) copolymers of various lengths and compositions to BSA. Subcutaneously administered BSA conjugate sols into the dorsal region of Sprague-Dawley rats formed an in situ gel. When the oligo(NIPAM) content in the hydrogel was high, the degradation rate of BSA hydrogels was remarkably slow, and two weeks after in vivo administration, the hydrogels with high oligo(NIPAM) had swollen more than 4-fold. An in vivo biodegradation study demonstrated that no necrosis or hemorrhage was observed in the tissues with the hydrogels. The concurrent stimuli-responsivity under physiological conditions and high elasticity suggest that these smart hydrogels may open a new avenue for hydrogel applications.

中文翻译:

工程性高度膨胀的基于双反应蛋白的可注射水凝胶:体内分子结构和组成的影响

刺激响应水凝胶,称为智能水凝胶,是三维两亲或亲水聚合物网络,能够根据pH,温度,和磁场或电场。通过化学缀合pH和温度响应性低聚物(丙烯酸磺胺甲嗪丙烯酸酯-co-N-异丙基丙烯酰胺)(oligo(SMA- co-NIPAM))通过碳二亚胺介导的化学反应在BSA表面上形成共聚物。带有pH和温度响应的低聚物的BSA共轭物显示出快速的溶胶-凝胶相变特性。具体而言,在生理条件(pH 7.4、37°C​​)下,高pH(pH 8.4,23°C)下自由流动的结合物转化为粘弹性凝胶。BSA水凝胶的溶胀率,凝胶强度和孔径可通过改变各种长度和组成的低聚物(SMA- co- NIPAM)与BSA的共轭比来调整。在Sprague-Dawley大鼠的背部区域中皮下注射BSA共轭溶胶形成了原位凝胶。当水凝胶中的低聚(NIPAM)含量高时,BSA水凝胶的降解速度显着缓慢,并且在体内给药两周后,高低聚(NIPAM)的水凝胶溶胀了4倍以上。的体内生物降解的研究表明,与水凝胶的组织中没有观察到坏死或出血。在生理条件和高弹性的同时刺激响应表明,这些智能水凝胶可能为水凝胶应用开辟一条新途径。
更新日期:2017-10-24
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