Hydrophilic Particles Exit While Hydrophobic Particles Persist Following In Vivo Biodegradation of Nanoparticle-Laden Polymeric Devices

Description

Longitudinally monitoring biomedical devices post-implantation can improve patient outcomes by allowing targeted intervention during healing. Most polymeric devices are not visible via biomedical imaging technologies. Incorporation of nanoparticle contrast agents into polymer matrices creates imageable devices, but understanding and controlling nanoparticle clearance from the implant site after polymer degradation is needed for clinical translation. To achieve homogeneous distribution throughout biomedical devices, nanoparticle surface chemistry, particularly hydrophobicity, is often manipulated to generate stable suspensions during manufacture. As nanoparticle surface chemistry is a key parameter determining blood circulation, the effects of nanoparticle hydrophilicity on tissue clearance of nanoparticles from implant sites following polymeric device degradation are investigated. Hydrophilic and hydrophobic radiopaque tantalum oxide (TaOx) nanoparticles are incorporated at 10 wt% tantalum into gelatin phantoms. In vitro, the diffusion coefficient of released hydrophilic nanoparticles after phantom degradation is significantly greater than hydrophobic nanoparticles. After subcutaneous implantation in mouse and subsequent phantom degradation, hydrophilic nanoparticles clear skin and muscle tissue within 24 h, whereas hydrophobic nanoparticles remained at the implant site >14 days without change in radiopacity. This clearly demonstrates that nanoparticle surface chemistry must be balanced for initial device manufacturing and final excretion. The files provided are micro-computed tomography scans in DICOM format from the in vivo study, including 7 timepoints in each individual; the study setup and implantation key are also provided to aide interpretation. The study is published as: Pawelec, K.M., Hix, J.M.L., Kiupel, M., Bonitatibus, P.J., Jr. and Shapiro, E.M. (2025), Hydrophilic Particles Exit While Hydrophobic Particles Persist Following In Vivo Biodegradation of Nanoparticle-Laden Polymeric Devices. Adv. NanoBiomed Res., 5: 2500005. https://doi.org/10.1002/anbr.202500005.

Steps to reproduce

Hydrophobic tantalum oxide (TaOx) nanoparticles were coated with an aliphatic organosilane (3-aminopropyl) trimethoxy silane (APTMS, Sigma). Hydrophilic nanoparticles were formulated with a zwitterionic coating. Phantoms were constructed from gelatin (Type A from porcine skin, Sigma G2625), to contain 10wt% gelatin and 10wt% tantalum. Solutions of 10wt% gelatin were first heated at 70°C until the gelatin was completely dissolved and clear. Just before casting in silicon molds, solutions were vortexed briefly. Each mold was filled with 40 μL of gelatin solution and allowed to gel. A Revvity Quantum GX was used for all micro computed tomography (µCT) imaging, operated at 90 keV, 88 µA. In vivo µCT on mice, post implantation scans were taken using a 72 mm field of view at 90 μm resolution. Scanning time points post-implantation were at 30 minutes and 180 minutes on day 0, then on days 1, 3, 7 and 14. To quantify the radiopacity and volume of phantoms post-implantation, ITK SNAP was utilized. Tissue containing nanoparticles was segmented from the background tissue using built in segmentation tools. Regions with nanoparticles were identified by increased X-ray attenuation. The volume of the tissue segmented and its average intensity was calculated for each time point. All procedures were performed in accordance with IACUC approved protocols and Veterinary guidelines at Michigan State University (PROTO202100337). FVB mice (n=6 adult male and female, > 9 months old; Charles River Laboratories) were used for this surgical implantation and µCT imaging study. Each mouse was surgically implanted with two gelatin phantoms containing either 0wt% or 10wt% TaOx nanoparticles (hydrophilic or hydrophobic) installed on opposite sides of the animal. Sterile phantoms, 4.7 mm diameter and 1.5 mm thick, were prepared on the day of implantation. The gelatin phantoms were implanted subcutaneously after creating a subcutaneous pocket, and placing a phantom inside before closing the site using Vetbond™ tissue glue (N-butyl cyanoacrylate). Post-operative clinical observation, body weight assessment, and health score assessments were performed for 7-14 days post-operatively.

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Funders

• National Institute of Biomedical Imaging and Bioengineering

  National Institutes of Health

  Bethesda

  Grant ID: R01EB029418

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