Fiber development and matrix production in tissue-engineered menisci using bovine mesenchymal stem cells and fibrochondrocytes

Abstract

Mesenchymal stem cells (MSCs) have been investigated with promising results for meniscus healing and tissue engineering. While MSCs are known to contribute to ECM production, less is known about how MSCs produce and align large organized fibers for application to tissue engineering the meniscus. The goal of this study was to investigate the capability of MSCs to produce and organize extracellular matrix molecules compared to meniscal fibrochondrocytes (FCCs). Bovine FCCs and MSCs were encapsulated in an anatomically accurate collagen meniscus using mono-culture and co-culture of each cell type. Each meniscus was mechanically anchored at the horns to mimic the physiological fixation by the meniscal entheses. Mechanical fixation generates a static mechanical boundary condition previously shown to induce formation of oriented fiber by FCCs. Samples were cultured for 4 weeks and then evaluated for biochemical composition and fiber development. MSCs increased the GAG and collagen production in both co-culture and mono-culture groups compared to FCC mono-culture. Collagen organization was greatest in the FCC mono-culture group. While MSCs had increased matrix production they lacked the fiber organization capabilities of FCCs. This study suggests that GAG production and fiber formation are linked. Co-culture can be used as a means of balancing the synthetic properties of MSCs and the matrix remodeling capabilities of FCCs for tissue engineering applications.

Meniscus beyond mechanics: Using biology to advance our understanding of meniscus injury and treatment

“…McCorry and Bonassar reveal that anatomically shaped meniscus collagen constructs composed of MSCs showed more collagen and glycosaminoglycan production, while constructs composed of meniscus fibrochondrocytes showed greater collagen organization (11). These findings suggest that co-culture of MSCs and fibrochondrocytes in tissue-engineered constructs may strike a balance between the synthetic phenotype of the MSCs and matrix remodeling phenotype of the fibrochondrocytes.…”

Next generation tissue engineering of orthopedic soft tissue-to-bone interfaces

“…[87–89,171] Mimicking this static mechanical boundary condition has shown organized fiber remodeling from several cell types including fibroblasts, [172–175] MSCs, [176–178] cardiomyocytes, [175] annulus fibrosis chondrocytes, [179] and meniscal fibrochondrocytes. [59,71,83] Mechanical anchoring at the bony ends of a soft tissue-to-bone model system directed longitudinal fiber formation as well as formed interdigitated fibers at the collagen-bone interface (Fig. 7C).…”

“…[180] MSCs in a tissue engineered meniscus also showed decreased fiber alignment and diameter compared to fibrochondrocytes. [83] These studies indicate that the response to mechanical stimuli is highly dependent on cell type.…”

Driving Hierarchical Collagen Fiber Formation for Functional Tendon, Ligament, and Meniscus Replacement

“…Recently, native sized 30-40 µm diameter collagen fibers were developed in a whole meniscus system using mechanical boundary constraints and high density collagen gels (10 -20 mg/ml) [20][21][22]. These are some of the largest fibers developed to date in engineered tissues, however the mechanical properties were lacking in comparison to native tissue, suggesting a need for further maturation.…”