Franz Schilling

Scaffolds with multiple advantageous biological and structural properties are still a challenge in the field of tissue engineering. The convergence of advanced fabrication techniques and functional materials is key to fulfill this need. Melt electrowriting (MEW) is an additive manufacturing technique that enables the fabrication of microfibrous scaffolds with precisely defined microarchitectures. Here, it is proposed to exploit metal–organic frameworks (MOFs) to efficiently introduce multifunctionalities by combining polycaprolactone (PCL), the gold standard material in MEW, with a silver‐/silver‐chloride‐decorated iron‐based MOF (NH 2 ‐MIL‐88B(Fe)). This results in highly ordered constructs with antibacterial properties and magnetic resonance imaging (MRI) visibility. Scaffolds with up to 20 wt% MOF are successfully melt‐electrowritten with a fiber diameter of 50 µm. Among these, 5 wt% MOF proves to be the optimal concentration as it exhibits silver‐induced sustained antibacterial efficacy while maintaining PCL cytocompatibility and in vitro immune response. The iron component of the MOF (Fe(III) nodes) renders the composite visible with MRI, thereby enabling scaffold monitoring upon implantation with a clinically accepted method. The combination of MEW and MOFs as tunable additives and cargo carriers opens the way for designing advanced multifunctional scaffolds with a wide range of applications in, e.g., tissue engineering, biosensing and drug delivery.

Metabolic magnetic resonance imaging (MRI) using hyperpolarized (HP) pyruvate is becoming a non‐invasive technique for diagnosing, staging, and monitoring response to treatment in cancer and other diseases. The clinically established method for producing HP pyruvate, dissolution dynamic nuclear polarization, however, is rather complex and slow. Signal Amplification By Reversible Exchange (SABRE) is an ultra‐fast and low‐cost method based on fast chemical exchange. Here, for the first time, we demonstrate not only in vivo utility, but also metabolic MRI with SABRE. We present a novel routine to produce aqueous HP [1‐ 13 C]pyruvate‐d 3 for injection in 6 minutes. The injected solution was sterile, non‐toxic, pH neutral and contained ≈30 mM [1‐ 13 C]pyruvate‐d 3 polarized to ≈11 % (residual 250 mM methanol and 20 μM catalyst). It was obtained by rapid solvent evaporation and metal filtering, which we detail in this manuscript. This achievement makes HP pyruvate MRI available to a wide biomedical community for fast metabolic imaging of living organisms.

Purpose To develop a high spatiotemporal resolution 3D dynamic pulse sequence for preclinical imaging of hyperpolarized [1‐ 13 C]pyruvate‐to‐[1‐ 13 C]lactate metabolism at 7T. Methods A standard 3D balanced SSFP (bSSFP) sequence was modified to enable alternating‐frequency excitations. RF pulses with 2.33 ms duration and 900 Hz FWHM were placed off‐resonance of the target metabolites, [1‐ 13 C]pyruvate (by approximately −245 Hz) and [1‐ 13 C]lactate (by approximately 735 Hz), to selectively excite those resonances. Relatively broad bandwidth (compared to those metabolites' chemical shift offset) permits a short TR of 6.29 ms, enabling higher spatiotemporal resolution. Bloch equation simulations of the bSSFP response profile guided the sequence parameter selection to minimize spectral contamination between metabolites and preserve magnetization over time. Results Bloch equation simulations, phantom studies, and in vivo studies demonstrated that the two target resonances could be cleanly imaged without substantial bSSFP banding artifacts and with little spectral contamination between lactate and pyruvate and from pyruvate hydrate. High spatiotemporal resolution 3D images were acquired of in vivo pyruvate‐lactate metabolism in healthy wild‐type and endogenous pancreatic tumor‐bearing mice, with 1.212 s acquisition time per single‐metabolite image and (1.75 mm) 3 isotropic voxels with full mouse abdomen 56 × 28 × 21 mm 3 FOV and fully‐sampled k‐space. Kidney and tumor lactate/pyruvate ratios of two consecutive measurements in one animal, 1 h apart, were consistent. Conclusion Spectrally selective bSSFP using off‐resonant RF excitations can provide high spatio‐temporal resolution 3D dynamic images of pyruvate‐lactate metabolic conversion.