Smart Collagen Hydrogels Based on 1-Ethyl-3-methylimidazolium Acetate and Microbial Transglutaminase for Potential Applications in Tissue Engineering and Cancer Therapy,ACS Biomaterials Science & Engineering

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Smart Collagen Hydrogels Based on 1-Ethyl-3-methylimidazolium Acetate and Microbial Transglutaminase for Potential Applications in Tissue Engineering and Cancer Therapy
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2019-06-12 00:00:00 , DOI: 10.1021/acsbiomaterials.9b00393
Xian Li _{1,

2} , Daidi Fan ₁

Affiliation

For the first time, collagen-based hydrogels were fabricated in the presence of a biocompatible ionic liquid, 1-ethyl-3-methylimidazolium acetate ([EMIM] [Ac]), by a simple biopolymer cross-linking process facilitated by the strong catalytic hydrolysis of microbial transglutaminase (MTGase). Phosphate buffer solution (PBS)-encapsulated human-like collagen (HLC) or fish bone collagen (FBC) for the composite hydrogels was simply prepared by the codissolution of biopolymers in [EMIM] [Ac] or, in the absence of the ionic liquid, by the dispersion of MTGase in the biopolymer solution, leading to the formation of MTGase-aided hydrogels (Gel1 and Gel4) and [EMIM] [Ac]/MTGase-aided hydrogels (Gel2, Gel3, and Gel5). The effects of different contents of [EMIM] [Ac] and collagens of different origins (HLC and FBC) during fabrication on a range of structural and material characteristics, including the synthesis mechanism, three-dimensional structure, swelling behavior, mechanical strength, enzymatic hydrolysis rate, cytotoxicity, fibroblast cell proliferation rate, in vitro inhibition of cancer cells and cell adhesion, and in vivo histocompatibility, were investigated. Surprisingly, fabrication with [EMIM] [Ac] had significant effects on the structure and properties of the collagen/MTGase-based hydrogels. In other words, [EMIM] [Ac] changed the underlying mechanism responsible for the advantageous properties of the hydrogels by changing the three-dimensional structure of HLC or FBC, which improved their effects on fibroblast proliferation (3T3-L1 and L929 cells) and their in vitro inhibition of cancer cells (HepG2 and MKN45 cells). The use of the ionic liquid also imbued the hydrogels with degradation resistance and anti-inflammatory properties after subcutaneous injection into mice (in vivo). The catalytic hydrolysis by MTGase and the [EMIM] [Ac] content were the major factors that influenced the properties of the collagen. This result suggests the potential application of ionic liquid-enzymatic hydrolysis in the fabrication of collagen hydrogels in circumstances where the control of the properties by an ionic liquid is desirable. Therefore, [EMIM] [Ac] could be a promising solvent for the development of collagen into smart biomaterials with controlled biodegradation rates that can meet the needs of specific potential applications, such as tissue engineering and cancer therapy.

中文翻译：

基于1-乙基-3-甲基咪唑鎓盐和微生物转谷氨酰胺酶的智能胶原蛋白水凝胶在组织工程和癌症治疗中的潜在应用

首次在生物相容性离子液体乙酸1-乙基-3-甲基咪唑鎓乙酸盐（[EMIM] [Ac]）存在下，通过简单的生物聚合物交联过程，通过强催化作用，制备了基于胶原蛋白的水凝胶。微生物转谷氨酰胺酶（MTGase）的水解。通过将生物聚合物共溶解在[EMIM] [Ac]中或在不存在离子液体的情况下，简单地制备了用于复合水凝胶的磷酸盐缓冲液（PBS）包裹的类人胶原（HLC）或鱼骨胶原（FBC）。通过将MTGase分散在生物聚合物溶液中，导致形成MTGase辅助的水凝胶（Gel1和Gel4）和[EMIM] [Ac] / MTGase辅助的水凝胶（Gel2，Gel3和Gel5）。研究了体外抑制癌细胞和细胞粘附以及体内组织相容性。令人惊讶地，用[EMIM] [Ac]制造对基于胶原/ MTGase的水凝胶的结构和性质具有显着影响。换句话说，[EMIM] [Ac]通过改变HLC或FBC的三维结构，从而改变了水凝胶有利特性的潜在机制，从而改善了它们对成纤维细胞（3T3-L1和L929细胞）增殖的影响，并且它们体外抑制癌细胞（HepG2和MKN45细胞）。皮下注射入小鼠体内后，使用离子液体还使水凝胶具有抗降解性和抗炎特性。）。MTGase的催化水解和[EMIM] [Ac]含量是影响胶原蛋白特性的主要因素。该结果表明在期望通过离子液体控制性质的情况下，离子液体酶水解在胶原水凝胶的制造中的潜在应用。因此，[EMIM] [Ac]可能是有前途的溶剂，可用于将胶原蛋白发展为具有可控制的生物降解速率的智能生物材料，以满足特定潜在应用的需求，例如组织工程和癌症治疗。

更新日期：2019-06-12

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