Biomedical-grade, high mannuronic acid content (BioMVM) alginate enhances the proteoglycan production of primary human meniscal fibrochondrocytes in a 3-D microenvironment

Abstract

Alginates are important hydrogels for meniscus tissue engineering as they support the meniscal fibrochondrocyte phenotype and proteoglycan production, the extracellular matrix (ECM) component chiefly responsible for its viscoelastic properties. Here, we systematically evaluated four biomedical- and two nonbiomedical-grade alginates for their capacity to provide the best three-dimensional (3-D) microenvironment and to support proteoglycan synthesis of encapsulated human meniscal fibrochondrocytes in vitro. Biomedical-grade, high mannuronic acid alginate spheres (BioLVM, BioMVM) were the most uniform in size, indicating an effect of the purity of alginate on the shape of the spheres. Interestingly, the purity of alginates did not affect cell viability. Of note, only fibrochondrocytes encapsulated in BioMVM alginate produced and retained significant amounts of proteoglycans. Following transplantation in an explant culture model, the alginate spheres containing fibrochondrocytes remained in close proximity with the meniscal tissue adjacent to the defect. The results reveal a promising role of BioMVM alginate to enhance the proteoglycan production of primary human meniscal fibrochondrocytes in a 3-D hydrogel microenvironment. These findings have significant implications for cell-based translational studies aiming at restoring lost meniscal tissue in regions containing high amounts of proteoglycans.

Selection of Effective Therapies Using Three-Dimensional in vitro Modeling of Chondrosarcoma

“…Following expansion in a monolayer, cell lines were suspended in 1.2% (w/v) medium viscosity alginic acid (Sigma-Aldrich, Darmstadt, Germany) in 0.15 M NaCl at 1 × 10 6 cell/mL density to generate spheroids (∼14,140 cells/bead). Concentrations of around 1% w/v alginate were deemed optimal for cartilageorientated in vitro and in vivo applications by several groups (Heiligenstein et al, 2011;Rey-Rico et al, 2016). Alginate beads were formed by dropping the cellular suspension in 1.2% (w/v) alginate/0.15 M NaCl (Sigma-Aldrich) through a 19-gauge needle into 0.2 M CaCl 2 solution (Sigma-Aldrich).…”

Tissue engineering of human knee meniscus using functionalized and reinforced silk‐polyvinyl alcohol composite three‐dimensional scaffolds: Understanding the in vitro and in vivo behavior

“…Different cell sources like stem cells, chondrocytes, and primary human meniscus cells have been studied for meniscus tissue engineering. Primary human meniscus cells isolated from surgical debris have been used as a potential cell source . The main advantage of tissue constructs derived from meniscus cells is the better histocompatibility, which makes them a potential source for meniscus tissue engineering.…”

“…Primary human meniscus cells isolated from surgical debris have been used as a potential cell source. [12][13][14] The main advantage of tissue constructs derived from meniscus cells is the better histocompatibility, 13 which makes them a potential source for meniscus tissue engineering. However, studies have reported that cells isolated from meniscus are not sufficient to satisfy the need for regeneration of tissue due to their poor proliferation capacity.…”

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“…Following expansion in a monolayer, cell lines were suspended in 1.2% (w/v) medium viscosity alginic acid (Sigma-Aldrich, Darmstadt, Germany) in 0.15 M NaCl at 1 × 10 6 cell/mL density to generate spheroids (∼14,140 cells/bead). Concentrations of around 1% w/v alginate were deemed optimal for cartilageorientated in vitro and in vivo applications by several groups (Heiligenstein et al, 2011;Rey-Rico et al, 2016). Alginate beads were formed by dropping the cellular suspension in 1.2% (w/v) alginate/0.15 M NaCl (Sigma-Aldrich) through a 19-gauge needle into 0.2 M CaCl 2 solution (Sigma-Aldrich).…”