Department of Physics and Chemistry, Alzahra University, Vanak Village Street, Tehran 19938 93973, Tehran Province, Iran.
Department of Physics and Chemistry, Alzahra University, Vanak Village Street, Tehran 19938 93973, Tehran Province, Iran.
Int J Biol Macromol. 2024 Nov;280(Pt 2):135749. doi: 10.1016/j.ijbiomac.2024.135749. Epub 2024 Sep 18.
The increasing demand for advanced biomaterials in nerve tissue engineering presents numerous challenges due to the complexity of nerve tissues and the need for materials that can accurately replicate their intricate structure and function. In response, this study introduces a novel injectable hydrogel that is thermosensitive, self-healing, and conductive, offering promising potential for heart and nerve tissue engineering applications. The hydrogel is based on collagen and hyaluronic acid functionalized with 3-aminopropyl-triethoxysilane (APTES)-grafted oxidized bacterial cellulose and gold nanoparticles (~50 nm). Rheological analysis reveals a substantial enhancement in the elastic modulus of the collagen-hyaluronic acid matrix with the incorporation of bacterial cellulose/gold nanoparticles, improving by an order of magnitude at 1 % strain. This improvement comes with a slight decrease in gelation temperature, from 36 °C to 32 °C. Besides thermo-sensitivity, the nanocomposite hydrogel exhibits a remarkable self-sealing response (about 80 % effectiveness) due to reversible physical crosslinking. Electrical spatial resistance measurements on human embryonic stem cell-derived cardiomyocytes-loaded hydrogels yield a value of ~0.1 S/m, which is suitable for electrical stimulation. In vitro extracellular field potential measurements also affirm the hydrogel's potential as an injectable scaffold for heart tissue engineering, i.e., the electrically stimulated human stem cells exhibit 47 beats per minute with a cell discharge (depletion) of 5.47 μv. A rapid gel formation in the physiological temperature (about 2 min) and high H9C2 cytotoxicity (viability of >90 % after 72 h incubation) is attainable. The developed collagen-based nanocomposite hydrogel offers an injectable, thermosensitive, and self-healing biomaterial platform for nerve or myocardium regeneration.
神经组织工程中对先进生物材料的需求不断增加，这带来了许多挑战，因为神经组织非常复杂，需要的材料能够准确复制其复杂的结构和功能。有鉴于此，本研究介绍了一种新型的可注射水凝胶，它具有温敏性、自修复性和导电性，有望在心脏和神经组织工程应用中得到应用。该水凝胶以胶原蛋白和透明质酸为基础，功能化的 3-氨基丙基三乙氧基硅烷（APTES）接枝氧化细菌纤维素和金纳米粒子（~50nm）。流变分析显示，细菌纤维素/金纳米粒子的加入使胶原蛋白-透明质酸基质的弹性模量显著提高，在 1%应变下提高了一个数量级。凝胶化温度略有下降，从 36°C 降至 32°C。除了温敏性之外，纳米复合水凝胶还表现出显著的自修复响应（约 80%的有效性），这是由于可逆的物理交联。对负载有人胚胎干细胞衍生的心肌细胞的水凝胶进行的电空间电阻测量得到的数值约为 0.1S/m，这适合电刺激。体外细胞外场电位测量也证实了水凝胶作为心脏组织工程可注射支架的潜力，即电刺激的人干细胞每分钟跳动 47 次，细胞放电（耗竭）为 5.47μv。在生理温度（约 2 分钟）下可快速形成凝胶，且对 H9C2 的细胞毒性（孵育 72 小时后存活率>90%）较高。所开发的基于胶原蛋白的纳米复合水凝胶为神经或心肌再生提供了一种可注射的、温敏性的和自修复的生物材料平台。
