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

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.

Single-cell RNA-seq analysis identifies meniscus progenitors and reveals the progression of meniscus degeneration

“…TGFβ is widely used in meniscus tissue engineering, owing to its promotion of meniscus injury repair and regeneration through the promotion of fibrochondrocyte proliferation and recruitment of meniscus progenitor cells 30 46 47. TGFβ also regulates the meniscus degeneration process, while the postnatal deletion of TGFβ signalling reporter ALK5 accelerates meniscus degeneration 31.…”

Advances in Tissue Engineering and Innovative Fabrication Techniques for 3-D-Structures: Translational Applications in Neurodegenerative Diseases

“…Indeed, the benefit of scaffold anisotropy was evident with human-induced pluripotent stem cell-derived cardiomyocytes, where parallel-aligned polymer scaffolds can provide contact guidance to cells to reorganize cellular orientation and differentiation [ 115 ]. Moreover, Zhang and colleagues applied biomechanical and biochemical stimuli to mesenchymal stem cells seeded into a biomimetic scaffold to induce the differentiation of fibrochondrocytes, resulting in physiological anisotropy in the engineered meniscus [ 116 ].…”

Three-dimensional bioprinting of multicell-laden scaffolds containing bone morphogenic protein-4 for promoting M2 macrophage polarization and accelerating bone defect repair in diabetes mellitus

“…However, for patients with DM, the local microenvironment at the region of the bone defect becomes inflamed, which can lead to vascular occlusion and reduced neovascularization, and because traditional 3D-printed scaffolds usually induce cell homing, local tissue responses, and functional stimulation, these scaffolds may use the host as a bioreactor to recruit host endogenous cells for tissue regeneration; therefore, the growth and viability of loaded cells is decreased in traditional 3D-printed scaffolds [ 5 , 6 , 8 , 9 ]. In addition, before in vivo transplantation, 3D-printed scaffolds require cell seeding and long-term cultivation in vitro, which increases the risk of infection and lengthens the time needed for surgery [ 10 , 11 ]. Recently, 3D bioprinting technology was developed to facilitate rapid bone defect repair.…”