Cellular and Chemical Gradients to Engineer the Meniscus‐to‐Bone Insertion

Abstract

Tissue‐engineered menisci hold promise as an alternative to allograft procedures but require a means of robust fixation to the native bone. The insertion of the meniscus into bone is critical for meniscal function and inclusion of a soft tissue‐to‐bone interface in a tissue engineered implant can aid in the fixation process. The native insertion is characterized by gradients in composition, tissue architecture, and cellular phenotype, which are all difficult to replicate. In this study, a soft tissue‐to‐bone interface is tissue engineered with a cellular gradient of fibrochondrocytes and mesenchymal stem cells and subjected to a biochemical gradient through a custom media diffusion bioreactor. These constructs, consisting of interpenetrating collagen and boney regions, display improved mechanical performance and collagen organization compared to controls without a cellular or chemical gradient. Media gradient exposure produces morphological features in the constructs that appear similar to the native tissue. Collectively, these data show that cellular and biochemical gradients improve integration between collagen and bone in a tissue engineered soft tissue‐to‐bone construct.

Driving Native-like Zonal Enthesis Formation in Engineered Ligaments Using Mechanical Boundary Conditions and β-Tricalcium Phosphate

“…Biochemical and mechanical stimulation are well established to further improve engineered tissue development [21,[43][44][45]61,62,75,76]. The addition of conditioned media or tissue specific growth factors has been shown to enhance zonal soft tissue-to-bone development [62,75,76]. Further, mechanical cues are well established to be essential to enthesis development [29,38,39], and thus addition of mechanical load could also further drive maturation of these tissues.…”

Top-Down Fabrication of Spatially Controlled Mineral-Gradient Scaffolds for Interfacial Tissue Engineering

“…[10][11][12] For example, these scaffolds could be applied to systems that use similar tissues to generate seamless interfacial structures. 32 These scaffolds would also be useful for analyzing cellular behavior in developmental systems. For example, seeding chondrocytes or other musculoskeletal cells onto interfacial scaffolds would allow for the in vitro study of cellular behavior during endochondral ossification or long bone growth directed from the growth plate.…”

“…Bone scaffolds were seeded as previously described. 32 Briefly, bone scaffolds were skewered and suspended in a spinner flask. The flask was supplied filled with 150 mL of osteogenic media containing 500,000 cells/bone scaffold and stored in an incubator for 48 hours.…”

Building Scaffolds for Tubular Tissue Engineering

“…In the case of some hydrogels, particularly biomolecular gels, e.g., collagen, fibrin, etc., cells can be cast with the gel ( Seliktar et al, 2003 ; Swartz et al, 2005 ; Liu et al, 2007 ; Naito et al, 2011 ; Atchison et al, 2017 , 2020 ). This method is convenient and widely applicable, as it can be used to produce a variety of geometries and shapes with homogenous cell populations and is compatible with other manufacturing methods ( Atchison et al, 2017 ; Iannucci et al, 2019 ). However, a secondary seeding step is often still necessary to create the stratified cellular structure of native tubular tissues, even when using homogeneously seeded hydrogels.…”