Noninvasive In Vivo Imaging and Monitoring of 3D-Printed Polycaprolactone Scaffolds Labeled with an NIR Region II Fluorescent Dye

Abstract

Significant progress has been made in fabricating porous scaffolds with ultrafine fibers for tissue regeneration. However, the lack of noninvasive tracking methods in vivo makes it impossible to track the fate of such scaffolds in situ. The development of near-infrared region II (NIR-II, 1000–1700 nm) dyes provides the possibility of performing noninvasive visualization with deep-tissue penetration and high spatial resolution in vivo. Herein, we developed a polycaprolactone (PCL) ink containing the small organic NIR-II dye SY-1030 and the fluorescently labeled macromolecular dye SY-COO-PCL and fabricated high-resolution NIR-II active scaffolds via electrohydrodynamic jet (EHDJ) printing. All printed scaffolds subcutaneously implanted in mice were clearly imaged one week after the operation. Compared with scaffolds containing SY-1030, the fluorescence intensity emitted from scaffolds containing SY-COO-PCL can be tracked for up to three weeks. Moreover, the image quality can be optimized by adjusting the dye concentration, laser power, and exposure time. The advantage of such NIR-II active scaffolds is evidenced by the lower dye concentration, longer tracking period, and better in vivo stability. We also demonstrated the biocompatibility and biodegradability of the scaffolds containing SY-COO-PCL over a 3-month period. The developed NIR-II active scaffolds have potential applications in biopolymer implant tracking, tissue reconstruction monitoring, and target-position-based drug delivery.

Three-Dimensional RAW264.7 Cell Model on Electrohydrodynamic Printed Poly(ε-Caprolactone) Scaffolds for In Vitro Study of Anti-Inflammatory Compounds

“…2 This differs from their natural growth manner where spherical macrophages are supported by neighboring cells and ECM 27 and thus lead to false positive anti-inflammatory compound screening results. 7,8 EHDJ is a highly precisely controlled 3D printing technology, and the EHDJ-printed scaffolds have been applied to culture various cell lines, for example, NIH/3T3 and A549 cells on PCL and PCL/zein scaffolds, 11,26 murine macrophages on NIR-II-dye-containing PCL scaffolds, 28 and human macrophages and PC12 cells on PCL scaffolds. 22,29 In all these studies, cells showed behaviors different from traditional in vitro cells and demonstrated their potential of biomimetic structural organization and application in tissue engineering.…”

Synthesis of New AIEE-Active Chalcones for Imaging of Mitochondria in Living Cells and Zebrafish In Vivo

“…In order to evaluate the application of compounds 1-6 in the biomedical field, we used an MTT assay to test the cytotoxicity of compounds 1-6 with different concentrations (1,3,6, and 12 µM) on A549 cells, respectively. As shown in Figure 7 below, after 24 h co-incubation of A549 cells with compounds 1-6, cell viability at various experimental concentrations was more than 80%, which indicates that compounds 1-6 have low cytotoxicity on and good cytocompatibility with A549 cells at the experimental concentrations.…”

“…Organic fluorescent dyes have been generally applied to biological imaging, fluorescent probes, pathological detection, and other fields on account of their strong fluorescence emission [1][2][3][4]. However, traditional organic fluorescent dyes often show an aggregation-caused quenching (ACQ) phenomenon, which severely limits their practical application.…”

Quantum dots-labeled polymeric scaffolds for in vivo tracking of degradation and tissue formation

“…Thus, there is an inevitable gap in scaffold degradation rates between in vitro and in vivo [ 15 , 16 ]. To track in vivo degradation of scaffolds, fluorescence labeling of scaffold materials has been applied [ [17] , [18] , [19] ]. For example, an organic fluorophore, di(thiophene-2-yl)-diketopyrrolopyrrole (DPP), was covalently linked in PCL that resulted in yellow fluorescence [ 17 ].…”

“…NIR signal at 800 nm emitted from the scaffold showed promising efficiency of tracing in vivo scaffold degradation [ 19 ]. Despite the promising outcome of the existing fluorescent polymers for in vivo tracking of degradation, the synthesis of fluorophore-conjugated materials requires complicated processes and unique facilities for quality control of the chemical reactions [ [17] , [18] , [19] ]. Moreover, a specific chemical modification needs to be implemented for optimal labeling for each biomaterial, consequently serving as a barrier for expanded applications.…”