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Background: A noninvasive method to track implanted biomaterials is desirable for real‐time monitoring of material interactions with host tissues and assessment of efficacy and safety. Purpose: To explore quantitative in vivo tracking of polyurethane implants using a manganese porphyrin (MnP) contrast agent containing a covalent binding site for pairing to polymers. Study Type: Prospective, longitudinal. Animal Model: Rodent model of dorsal subcutaneous implants (10 female Sprague Dawley rats). Field Strength/Sequence: A 3‐T; two‐dimensional (2D) T1‐weighted spin‐echo (SE), T2‐weighted turbo SE, three‐dimensional (3D) spoiled gradient‐echo T1 mapping with variable flip angles. Assessment: A new MnP‐vinyl contrast agent to covalently label polyurethane hydrogels was synthesized and chemically characterized. Stability of binding was assessed in vitro. MRI was performed in vitro on unlabeled hydrogels and hydrogels labeled at different concentrations, and in vivo on rats with unlabeled and labeled hydrogels implanted dorsally. In vivo MRI was performed at 1, 3, 5, and 7 weeks postimplantation. Implants were easily identified on T1‐weighted SE, and fluid accumulation from inflammation was distinguished on T2‐weighted turbo SE. Implants were segmented on contiguous T1‐weighted SPGR slices using a threshold of 1.8 times the background muscle signal intensity; implant volume and mean T1 values were then calculated at each timepoint. Histopathology was performed on implants in the same plane as MRI and compared to imaging results. Statistical Tests: Unpaired t‐tests and one‐way analysis of variance (ANOVA) were used for comparisons. A P value <0.05 was considered to be statistically significant. Results: Hydrogel labeling with MnP resulted in a significant T1 reduction in vitro (T1 = 517 ± 36 msec vs. 879 ± 147 msec unlabeled). Mean T1 values of labeled implants in rats increased significantly by 23% over time, from 1 to 7 weeks postimplantation (651 ± 49 msec to 801 ± 72 msec), indicating decreasing implant density. Data Conclusion: Polymer‐binding MnP enables in vivo tracking of vinyl‐group coupling polymers. Evidence Level: 1. Technical Efficacy: Stage 1. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) contrast agents, in contrast to the plethora of fluorescent agents available to target disease biomarkers or exogenous implants, have remained predominantly non-specific. That is, they do not preferentially accumulate in specific locations in vivo because doing so necessitates longer contrast retention, which is contraindicated for current gadolinium (Gd) agents. This double-edge sword implies that Gd agents can offer either rapid elimination (but lack specificity) or targeted accumulation (but with toxicity risks). For this reason, MRI contrast agent innovation has been severely constrained. Gd-free alternatives based on manganese (Mn) chelates have been largely ineffective, as they are inherently unstable. In this study, we present a Mn(III) porphyrin (MnP) platform for bioconjugation, offering the highest stability and chemical versatility compared to any other T1 contrast agent. We exploit the inherent metal stability conferred by porphyrins and the absence of pendant bases (found in Gd or Mn chelates) that limit versatile functionalization. As proof-of-principle, we demonstrate labeling of human serum albumin, a model protein, and collagen hydrogels for applications in in-vivo targeted imaging and material tracking, respectively. In-vitro and in-vivo results confirm unprecedented metal stability, ease of functionalization, and high T1 relaxivity. This new platform opens the door to ex-vivo validation by fluorescent imaging and multipurpose molecular imaging in vivo. [ABSTRACT FROM AUTHOR]

Background: A three‐dimensional (3D) bioprinted tissue scaffold is a promising therapeutic that goes beyond providing physical support for tissue regeneration by enabling precise spatial control over scaffold geometry and integration of different materials/cells. Critically important is in vivo confirmation of correct scaffold placement and retention during the initial 24 hours postimplantation, to detect unwanted implant migration. Purpose: To incorporate a safe, efficient MR contrast agent into a bioprinting workflow, and to achieve bright‐contrast scaffold monitoring in vivo postimplantation. Study Type: In vitro and animal in vivo longitudinal study. Animal Model: Two female Sprague Dawley rats (~200 g) for labeled and unlabeled scaffold implantation in the subcutaneous dorsal space flanking the vertebral column. Field Strength/Sequence: A 7.0 T/T1‐weighted spin echo (SE) sequence and T1 mapping using turbo SE with variable repetition times (TRs). Assessment: Cell viability and proliferation were assessed over 2 weeks after labeling bioprinted gelatin/alginate scaffolds with MnPNH2 (0.5 mM, 24 hours). In vitro MRI was performed 0, 12, and 24 hours postlabeling in nine labeled and three unlabeled (control) scaffolds to monitor T1 evolution. In vivo MRI was performed immediately and 24 hours postimplantation to assess T1. Acute inflammation near surgical site was monitored in one rat to 3 days. Statistical Tests: One‐way analysis of variance with Tukey–Kramer post hoc analysis (P < 0.01). Results: Cell viability was unaffected by bioprinting/labeling: viability exceeded 90% in all scaffolds after 1 week. In vitro T1's were significantly lower in labeled scaffolds compared to control (207 msec vs. 2257 msec) immediately postlabeling and 24 hours later (1227 msec vs. 2257 msec). In vivo T1's were significantly different (243.6 msec vs. 2414.6 msec) immediately postimplantation, and no differences emerged compared to respective in vitro control/labeled counterparts. The 24‐hours imaging and gross pathology confirmed migration of scaffolds beyond the imaging field. Data Conclusion: We report an MR‐detectable, cell‐compatible bioprinted scaffold, utilizing a T1‐weighting contrast agent for high‐resolution, postimplantation scaffold tracking. Evidence Level: 2 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]