Imaging the In Vivo Degradation of Tissue Engineering Implants by Use of Supramolecular Radiopaque Biomaterials

Abstract

For in situ tissue engineering (TE) applications it is important that implant degradation proceeds in concord with neo‐tissue formation to avoid graft failure. It will therefore be valuable to have an imaging contrast agent (CA) available that can report on the degrading implant. For this purpose, a biodegradable radiopaque biomaterial is presented, modularly composed of a bisurea chain‐extended polycaprolactone (PCL2000‐U4U) elastomer and a novel iodinated bisurea‐modified CA additive (I‐U4U). Supramolecular hydrogen bonding interactions between the components ensure their intimate mixing. Porous implant TE‐grafts are prepared by simply electrospinning a solution containing PCL2000‐U4U and I‐U4U. Rats receive an aortic interposition graft, either composed of only PCL2000‐U4U (control) or of PCL2000‐U4U and I‐U4U (test). The grafts are explanted for analysis at three time points over a 1‐month period. Computed tomography imaging of the test group implants prior to explantation shows a decrease in iodide volume and density over time. Explant analysis also indicates scaffold degradation. (Immuno)histochemistry shows comparable cellular contents and a similar neo‐tissue formation process for test and control group, demonstrating that the CA does not have apparent adverse effects. A supramolecular approach to create solid radiopaque biomaterials can therefore be used to noninvasively monitor the biodegradation of synthetic implants.

Methacrylate‐Modified Gold Nanoparticles Enable Noninvasive Monitoring of Photocrosslinked Hydrogel Scaffolds

“…Previous studies investigating in vitro and in vivo micro‐CT imaging and monitoring degradation of hydrogel or polymeric scaffolds have generally used greater contrast agent concentrations, including 100 m m Gd 2 O 3 NPs, [ 28 ] 80 m m (≈13.6 wt%) Au NPs, [ 29 ] 20 wt% Au NPs, [ 62 ] 100 mg mL −1 iohexol (≈365 m m iodine), [ 30 ] and 11.4 wt% (≈500 m m ) iodine. [ 63 ] Of particular note, 50 m m TaO x NPs were reported to provide sufficient signal/noise within tissue phantoms for clinical CT imaging. [ 64 ] On the other hand, another study reported in vivo micro‐CT imaging of 3D‐printed gelMA + Au scaffolds comprising 0.16 m m Au NPs, [ 38 ] but did not report X‐ray attenuation in Hounsfield units (HU) making interpretation difficult.…”

Bioactive Scaffold With Spatially Embedded Growth Factors Promotes Bone-to-Tendon Interface Healing of Chronic Rotator Cuff Tear in Rabbit Model

“…For application of biodegradable scaffolds in large preclinical animal models and human patients, in vivo biodegradation has to be adjusted to balance with a tissue-healing rate. 46 The scaffolds’ in vivo degradation rate was preoptimized by controlling the surface porosity, as demonstrated in previous studies, 47,50 resulting in full degradation in the rabbit model by 12 weeks. However, the in vivo degradation rate of polyester scaffolds can be affected by local biological, chemical, and physical environments, 28,50 necessitating further adjustments for large animal models or human clinical trials.…”

Advocating Electrically Conductive Scaffolds with Low Immunogenicity for Biomedical Applications: A Review

“…Electron paramagnetic resonance (EPR) is an efficient and accurate technique to investigate radical and oxidative stresses [ 83 ]. Ultrasound elasticity imaging (UEI) can be used to characterise the structural, functional, and compositional changes of biodegradable scaffolds via phase-sensitive speckle tracking [ 84 , 85 ]. Several non-invasive and non-destructive techniques to investigate parameters such as a scaffold’s pH value, distribution, and cell viability are: (i) confocal laser scanning microscopy (CLSM); (ii) nuclear magnetic resonance (NMR); (iii) optical coherence microscopy (OCM); (iv) optical coherence tomography (OCT).…”