Dual-modal non-invasive imaging in vitro and in vivo monitoring degradation of PLGA scaffold based gold nanoclusters

Abstract

Biodegradable scaffolds play an important role in tissue engineering, and appropriate degradation and resorption rates of these scaffolds are necessary to accommodate tissue growth. Synthetic polymers are frequently used because of their ease of production, good biocompatibility and controllable degradation rates. However, monitoring the degradation of these polymers in vivo by a noninvasive approach remains limited. In this study, we designed a composite scaffold by labeling poly(lactic-co-glycolic acid) (PLGA) with gold nanoclusters (Au NCs), which were used for tracking in vivo degradation through dual-modal fluorescence/computed tomography (CT) imaging. The diameter of the Au NCs was approximately 2.5 nm, and the emission peak was at a wavelength of 700 nm. After labeling PLGA with the Au NCs, the fluorescence intensity of the Au NC/PLGA composite scaffold reached 9.0 × 10⁹ (p/s/cm²/sr)/(μW/cm²), and the CT density of the scaffold increased to 200 HU. After the composite scaffold was implanted subcutaneously into nude mice, a continuous decrease in the fluorescence signal and CT value was observed. The mean fluorescence intensity was 8.3 × 10⁹, 3.17 × 10⁹, 2.26 × 10⁹, 2.11 × 10⁹, and 1.82 × 10⁹ (p/s/cm²/sr)/(μW/cm²) from the first week to the fifth week, respectively. The mean CT value changed from 222.6 to 185.9, 149.1, 112.5, and 55.2 (Hounsfield unit, HU) at the different timepoints. Compared with the change in the fluorescence intensity, the change in the CT value was similar to the change in the weight, and the Pearson correlation coefficient between the change in the CT value and weight was 0.8626. Furthermore, the structure and morphology of the scaffolds at different timepoints were analyzed by three-dimensional (3-D) reconstruction. This novel method of noninvasive dynamic monitoring of biodegradable polymers in vivo provides insight into choosing suitable biomaterials for tissue engineering and regenerative medicine.

Keywords: Biodegradable polymer; CT imaging; Fluorescence imaging; Gold nanoclusters; Non-invasive imaging.