Orthopedic Regenerative Engineering: Future Treatments of Human Meniscus Lesions with a Patient-Specific Concept

Meniscus lesions are the most frequent lesions in the knee [1]. The current strategies for the transplantation of meniscus should be strengthened to tackle the faced limitations of current methods in the clinics. The main outstanding challenges in meniscus regeneration include the biological and biomechanical requirements that are linked with implant’s patient-specificity regarding the cells [2], and implant geometry [3]. Six fresh human lateral meniscus tissues were cut prepared into histological slices stained with Giemsa [2] and cells were counted with an in-depth fashion to obtain the 3D cellular density. High-quality MRI volumetric images were acquired from five healthy male human subjects. The advanced segmentation software was used for semi-automatic MRI image segmentation of the meniscus tissues. The obtained 3D models were used for the fabrication of tissue engineering scaffolds with different internal architectures. The 3D cellular density in the vascular region (27199 cells/mm³) was significantly higher as compared to the avascular region (12820 cells/mm³). MRI image dataset was processed into the 3D models by the segmentation of the MRI datasets were used to produce scaffolds [4]. The architecture A was composed of 90° and 0° strand structures, and the architecture B was composed of 90°, 45°, 0°, and 135° strand structures with 1 mm distance from each other for both architectures. The present study has addressed important aspects related to (i) the 3D cellular density of the human meniscus, and (ii) a methodology for the fabrication of 3D printed patient-specific scaffolds using patient’s knee MRI. The human lateral meniscus was quantitatively investigated for the cell morphology-specific 3D cellular density in a segmental and regional manner with respect to the laterality. The results provided useful information for meniscus tissue engineering by indicating the minimum cellular density with respect to the ratio of cell populations with distinct cell morphologies. These valuable insights on the 3D cellularity of the meniscus can open up the development of cell-based strategies in order to emulate the native tissue and manage meniscus regeneration adequately. Patient-specificity of an implant is of critical importance in the clinics, and herein a methodology of segmenting meniscus tissues from volumetric MRI datasets was demonstrated. This work brings us a step closer to the development of patient-specific meniscal implants and translation of personalized tissue engineering into daily clinical approaches when treatment of meniscus lesions is envisioned.

Acknowledgments

This work is a result of the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The authors also thank the financial support of the MultiScaleHuman project (Contract number: MRTN-CT-2011-289897) in the Marie Curie Actions-Initial Training Networks. I.F. Cengiz thanks the Portuguese Foundation for Science and Technology (FCT) for the Ph.D. scholarship (SFRH/BD/99555/2014). J.M. Oliveira also thanks the FCT for the funds provided under the program Investigador FCT 2012 and 2015 (IF/00423/2012 and IF/01285/2015).

References

1.Cengiz, I.F., et al. "Treatments of Meniscus Lesions of the Knee: Current Concepts and Future Perspectives." Regenerative Engineering and Translational Medicine 3.1 (2017): 32-50.

2.Cengiz I.F., et al., “Segmental and Regional Quantification of 3D Cellular Density of Human Meniscus from Osteoarthritic Knee”, Journal of tissue engineering and regenerative medicine 11.6 (2017): 1844-1852.

3.Cengiz, I.F., et al. "Building the basis for patient-specific meniscal scaffolds: from human knee MRI to fabrication of 3D printed scaffolds." Bioprinting 1 (2016): 1-10.

4.Cengiz, I.F., et al. "Building the Basis for Patient-Specific Meniscal Scaffolds." Bio-orthopaedics. Springer, Berlin, Heidelberg, 2017. 411-418.