This
study aimed to evaluate, for the first time, implantable,
biodegradable fiducial markers (FMs), which were designed for bimodal,
near-infrared fluorescence-based (NIRF) and X-ray-based imaging. The
developed FMs had poly(l-lactide-co-caprolactone)-based
core–shell structures made of radiopaque (core) and fluorescent
(shell) composites with a poly(l-lactide-co-caprolactone) matrix. The approved for human use contrast agents
were utilized as fillers. Indocyanine green was applied to the shell
material, whereas in the core materials, iohexol and barium sulfate
were compared. Moreover, the possibility of tailoring the stability
of the properties of the core materials by the addition of hydroxyapatite
(HAp) was examined. The performed in situ (porcine
tissue) and in vivo experiment (rat model) confirmed
that the developed FMs possessed pronounced contrasting properties
in NIRF and X-ray imaging. The presence of HAp improved the radiopacity
of FMs at the initial state. It was also proved that, in iohexol-containing
FMs, the presence of HAp slightly decreased the stability of contrasting
properties, while in BaSO4-containing ones, changes were
less pronounced. A comprehensive material analysis explaining the
differences in the stability of the contrasting properties was also
presented. The tissue response around the FMs with composite cores
was comparable to that of the FMs with a pristine polymeric core.
The developed composite FMs did not cause serious adverse effects
on the surrounding tissues even when irradiated in vivo. The developed FMs ensured good visibility for NIRF image-supported
tumor surgery and the following X-ray image-guided radiotherapy. Moreover,
this study replenishes a scanty report regarding similar biodegradable
composite materials with a high potential for application.