Biology, Biomechanics and Scaffolds

Associated with the publications: Pereira, H., et al. "Biomechanical and cellular segmental characterization of human meniscus: building the basis for Tissue Engineering therapies." Osteoarthritis and cartilage22.9 (2014): 1271-1281, and Pereira, Hélder, et al. "Human meniscus: from biology to tissue engineering strategies." Sports Injuries. Springer Berlin Heidelberg, 2015. 1089-1102.

To overcome current limitations of Tissue Engineering (TE) strategies, deeper comprehension on meniscus biology is required. This study aims to combine biomechanical segmental analysis of fresh human meniscus tissues and its correlation with architectural and cellular characterization. Method: Morphologically intact menisci, from 44 live donors were studied after division into three radial segments. Dynamic mechanical analysis (DMA) was performed at physiological-like conditions. Micro-computed tomography (CT) analysis of freeze-dried samples assessed micro-structure. Flow cytometry, histology and histomorphometry were used for cellular study and quantification. Results: Anterior segments present significantly higher damping properties. Mid body fresh medial meniscus presents higher values of E' compared to lateral. Cyclic loads influence the viscoelastic behavior of menisci. By increasing the frequency leads to an increase in stiffness. Conversely, with increasing frequencies, the capacity to dissipate energy and damping properties initially decrease and then rise again. Age and gender directly correlate with higher E' and tan δ. Micro-CT analysis revealed that mean porosity was 55.5 (21.2-89.8)% and 64.7 (47.7-81.8)% for freeze-dried lateral and medial meniscus, respectively. Predominant cells are positive for CD44, CD73, CD90 and CD105, and lack CD31, CD34 and CD45 (present in smaller populations). Histomorphometry revealed that cellularity decreases from vascular zone 1 to zone 3. Anterior segments of lateral and medial meniscus have inferior cellularity as compared to mid body and posterior ones. Conclusion: Menisci are not uniform structures. Anterior segments have lower cellularity and higher damping. Cyclic loads influence viscoelastic characteristics. Future TE therapies should consider segmental architecture, cellularity and biomechanics of fresh tissue

Once meniscus is damaged, a cascade of events occurs leading to degenerative joint changes of the knee. The morbidity of patients can significantly increase overtime and degeneration of the cartilage can progress, resulting in arthritis. Possibilities for treatment of meniscus lesions are primordially focused in repair and replacement (e.g., acellular scaffolds and meniscus allograft transplantation). Tissue Engineering and Regenerative Medicine have been providing new options in medical practice. However, these disciplines require deep understanding of the target tissue and physiopathology of the implicated disorder. In order to overcome the current limitations, fundamental studies have been made for developing reliable strategies aiming to obtain superior tissue healing. Herein, it is presented the most relevant insights and research directions on the fundamental biology and biomechanics of meniscus. The principles of tissue engineering (triad) and the significant in vitro and in vivo reports addressing meniscus regeneration are included, once these will provide the basements for future clinical directions.