Research ArticleTissue Engineering

Orchestrated biomechanical, structural, and biochemical stimuli for engineering anisotropic meniscus

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Science Translational Medicine  10 Apr 2019:
Vol. 11, Issue 487, eaao0750
DOI: 10.1126/scitranslmed.aao0750

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Engineering anisotropy

The meniscus is a fibrocartilage structure within a joint that helps reduce friction during joint movement. The outer and inner regions within the knee meniscus differ in cell types, extracellular matrix components, organization, and corresponding mechanical properties (anisotropy). Here, Zhang et al. used biomechanical stimulation and growth factor treatment during culture of mesenchymal stem cell–seeded polymer scaffolds to generate tissue constructs that mimic the native knee meniscus. The engineered meniscus constructs demonstrated long-term chondroprotection when implanted into the knees of rabbits. This study helps guide tissue engineering efforts to generate anisotropic constructs.

Abstract

Reconstruction of the anisotropic structure and proper function of the knee meniscus remains an important challenge to overcome, because the complexity of the zonal tissue organization in the meniscus has important roles in load bearing and shock absorption. Current tissue engineering solutions for meniscus reconstruction have failed to achieve and maintain the proper function in vivo because they have generated homogeneous tissues, leading to long-term joint degeneration. To address this challenge, we applied biomechanical and biochemical stimuli to mesenchymal stem cells seeded into a biomimetic scaffold to induce spatial regulation of fibrochondrocyte differentiation, resulting in physiological anisotropy in the engineered meniscus. Using a customized dynamic tension-compression loading system in conjunction with two growth factors, we induced zonal, layer-specific expression of type I and type II collagens with similar structure and function to those present in the native meniscus tissue. Engineered meniscus demonstrated long-term chondroprotection of the knee joint in a rabbit model. This study simultaneously applied biomechanical, biochemical, and structural cues to achieve anisotropic reconstruction of the meniscus, demonstrating the utility of anisotropic engineered meniscus for long-term knee chondroprotection in vivo.

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