Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150001, PR China.
Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150001, PR China.
Biomaterials. 2017 Nov;145:192-206. doi: 10.1016/j.biomaterials.2017.08.039. Epub 2017 Aug 26.
Visual in vivo degradation of hydrogel by fluorescence-related tracking and monitoring is crucial for quantitatively depicting the degradation profile of hydrogel in a real-time and non-invasive manner. However, the commonly used fluorescent imaging usually encounters limitations, such as intrinsic photobleaching of organic fluorophores and uncertain perturbation of degradation induced by the change in molecular structure of hydrogel. To address these problems, we employed photoluminescent carbon nanodots (CNDs) with low photobleaching, red emission and good biocompatibility as fluorescent indicator for real-time and non-invasive visual in vitro/in vivo degradation of injectable hydrogels that are mixed with CNDs. The in vitro/in vivo toxicity results suggested that CNDs were nontoxic. The embedded CNDs in hydrogels did not diffuse outside in the absence of hydrogel degradation. We had acquired similar degradation kinetics (PBS-Enzyme) between gravimetric and visual determination, and established mathematical equation to quantitatively depict in vitro degradation profile of hydrogels for the predication of in vivo hydrogel degradation. Based on the in vitro data, we developed a visual platform that could quantitatively depict in vivo degradation behavior of new injectable biomaterials by real-time and non-invasive fluorescence tracking. This fluorescence-related visual imaging methodology could be applied to subcutaneous degradation of injectable hydrogel with down to 7 mm depth in small animal trials so far. This fluorescence-related visual imaging methodology holds great potentials for rational design and convenient in vivo screening of biocompatible and biodegradable injectable hydrogels in tissue engineering.
通过荧光相关跟踪和监测来直观地观察水凝胶的体内降解对于实时、非侵入性地定量描绘水凝胶的降解情况至关重要。然而，常用的荧光成像通常会遇到一些限制，如有机荧光团的固有荧光猝灭以及水凝胶分子结构变化引起的降解不确定性的影响。为了解决这些问题，我们采用了具有低荧光猝灭、红色发射和良好生物相容性的光致发光碳纳米点（CNDs）作为荧光指示剂，用于实时、非侵入性地直观观察与体外/体内降解可注射水凝胶，这些水凝胶是与 CNDs 混合而成的。体外/体内毒性结果表明 CNDs 无毒。在没有水凝胶降解的情况下，嵌入水凝胶中的 CNDs 不会扩散到外部。我们已经获得了相似的降解动力学（PBS-Enzyme），通过重量法和直观测定法，并建立了数学方程来定量描述水凝胶的体外降解情况，从而预测体内水凝胶的降解情况。基于体外数据，我们开发了一个可视化平台，可以通过实时、非侵入性的荧光跟踪来定量描述新的可注射生物材料的体内降解行为。这种荧光相关的可视化成像方法可应用于小动物试验中可注射水凝胶的皮下降解，深度低至 7mm。这种荧光相关的可视化成像方法在组织工程中对于合理设计和方便体内筛选生物相容性和可生物降解的可注射水凝胶具有巨大的潜力。
