Tissue engineering of the synovial joint: The role of cell density

Abstract

The ultimate goal in the tissue engineering of the synovial joint is to fabricate biologically derived analogues that can replace severely degenerated or traumatized synovial joint components. A number of challenges must be addressed before reaching this ultimate goal. In this report, the relevance of cell seeding density in the synthesis of chondrogenic and osteogenic matrices from human mesenchymal stem cells is explored. Human mesenchymal stem cells (hMSCs) were differentiated into chondrogenic cells and osteogenic cells ex vivo and encapsulated in poly(ethylene glycol) diacrylate (PEGDA) hydrogel at densities of 5 x 106 cells/ml, 40 x 10(6) cells/ml, and 80 x 10(6) cells/ml, in addition to a cell-free poly(ethylene glycol) (PEG) control group (0 x 10(6) cells/ml). Cell-seeded or cell-free PEG constructs were separately incubated in vitro for 4 weeks or implanted in vivo in the dorsum of immunodeficient rats for 4 weeks. In-vitro data demonstrated that hMSC-derived chondrocytes or hMSC-derived osteoblasts maintained their lineages per Safranin O and von Kossa staining after incubation for 4 weeks. The general pattern of initial cell seeding densities of 5 x 10(6) cells/ml, 40 x 10(6) cells/ml, and 80 x 10(6) cells/ml were preserved following in-vitro cultivation. Similarly, in-vivo data revealed that hMSC-derived chondrocytes and hMSC-derived osteoblasts maintained their respective lineages and the pattern of cell-seeding densities. An attempt was made to fabricate a composite construct with PEGDA hydrogel and polycaprolactone (PCL) with designed internal porosity for an osteochondral graft. Various cell-seeding densities as delineated in this report can be realized in the composite PEG-PCL graft. The findings demonstrate that cell-seeding density is likely a key parameter to consider in tissue-engineering design. The source of cells can either be transplanted cells or internally recruited cells.

An adaptable hydrogel array format for 3-dimensional cell culture and analysis

“…This range is arbitrarily chosen and could likely be expanded by increasing or decreasing the cell density in the hydrogel precursor solution. The ability to vary cell density is important in view of previous studies, which have shown that changes in cell density in 3-D PEG hydrogels strongly influence cell survival and differentiated function [44]. Herein we found that NIH-3T3 cell viability is improved after 7 days of culture at high cell seeding densities when compared with culture at lower seeding densities (Fig.…”

One-Step Surgical Procedure for the Treatment of Osteochondral Defects with Adipose-Derived Stem Cells in a Caprine Knee Defect: A Pilot Study

“…This would match well with data on the structural organization of cartilage tissue describing a cellular density of 24,000 cells/mm 3 at the articular surface decreasing 3.5-fold to about 7000 cells/mm 3 at the lower half of the upper radial zone 42 and with studies emphasizing high density to favor chondrogenesis. 43,44 Currently it is unclear whether application of even higher cell densities would give better results, and this might certainly be interesting to investigate in future experiments.…”

Characteristics of Mesenchymal Stem Cells Originating from the Bilateral Inferior Turbinate in Humans with Nasal Septal Deviation

“…Recent findings suggest that a decline in the numbers, proliferation, or potential of stem cell populations in adult organs may contribute to characteristics of human aging, such as the decline in bone mass and age-related diseases including osteoarthritis and osteoporosis [16], [17]. In addition, although it has not been reported that a greater number of mesenchymal stem cells in the tissue increases its volume, Troken et al[18] suggested that higher mesenchymal stem cell densities yielded more marked matrix synthesis in vivo implantation. Mineral apposition is not attenuated by seeding hMSC-derived osteoblasts at a high density or in close proximity to each other.…”