Three-Dimensional Bioprinted MR-Trackable Regenerative Scaffold for Postimplantation Monitoring on T1-Weighted MRI.

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.