Lung Biopsy Tract Sealant and Fiducial Marker Based on a Hydrogel/Shape Memory Polymer Foam Composite With Multimodal...

Lung tissue biopsies can result in a collapsed lung in the patient via leakage of air (pneumothorax) from an open biopsy tract. To reduce the risk of pneumothorax, clinicians will implant a sealant to prevent leakage of air from the tract. However, current technologies used in the clinic have been proven to be ineffective in preventing pneumothorax and do not have any imaging contrast for visualization of the device and tissue of interest in post-op imaging. We have previously developed a biopsy tract plug based on a shape memory polymer foam and poly(ethylene glycol) hydrogel composite. Here, we are building on our previous work by developing a composite with magnetic resonance imaging (MRI) and computed tomography (CT) contrast so that it may function as a lung biopsy tract sealant as well as a fiducial marker. A peptide-based, norbornene-functionalized gadolinium chelate was synthesized via solid-phase peptide synthesis. This norbornene-functionalized gadolinium chelate will covalently bond into our thiol-ene crosslinked PEG hydrogel. Swelling kinetics and rheology showed that the incorporation of this chelate into the hydrogel network reduced swelling and increased equilibrium storage modulus of the hydrogel, respectively. Composites were fabricated with the gadolinium chelate (MR contrast agent) within the hydrogel network and two platinum marker bands (CT contrast agent) adhered at each end. Characterization revealed that the addition of the multimodal contrast did not affect the cytocompatibility of the composites but delayed their shape recovery. However, this delay proved beneficial for the effective deployment of the devices after exposure to water within the device housing for 2 min. Furthermore, this delay did not affect their ability to seal lung biopsy tracts in vitro. Composites were distinguishable from their surrounding tissue under MRI in vitro in a lung phantom and ex vivo in bovine liver. Finally, in vivo implantation showed that the composites maintained their MRI and CT contrast up to 4 weeks after subcutaneous implantation in mice without inducing a severe immune response to the local tissue or renal injury. Collectively, these results show that the composites with multimodal contrast have potential to serve as both lung biopsy sealants as well as fiducial markers.