Does tranexamic acid stabilised fibrin support the osteogenic differentiation of human periosteum derived cells?

Abstract

Fibrin sealants have long been used as carrier for osteogenic cells in bone regeneration. However, it has not been demonstrated whether fibrin's role is limited to delivering cells to the bone defect or whether fibrin enhances osteogenesis. This study investigated fibrin's influence on the behaviour of human periosteum-derived cells (hPDCs) when cultured in vitro under osteogenic conditions in two-dimensional (fibrin substrate) and three-dimensional (fibrin carrier) environments. Tranexamic acid (TEA) was used to reduce fibrin degradation after investigating its effect on hPDCs in monolayer culture on plastic.TEA did not affect proliferation nor calcium deposition of hPDCs under these conditions. Expression profiles of specific osteogenic markers were also maintained within the presence of TEA, apart from reduced alkaline phosphatase (ALP) expression (day 14). Compared to plastic, proliferation was upregulated on 2D fibrin substrates with a 220% higher DNA content by day 21. Gene expression was also altered, with significantly (p<0.05) decreased Runx2 (day 7) and ALP (day 14) expression and increased collagen I expression (day 14 and 21). In contrast to plastic, mineralisation was absent on fibrin substrates. Inside fibrin carriers, hPDCs were uniformly distributed. Moderate cell growth and reduced osteogenic marker expression was observed inside fibrin carriers. After 2 weeks, increased cell death was present in the carrier's centre. In conclusion, fibrin negatively influences osteogenic differentiation, compared to culture plastic, but enhanced proliferation (at least in 2D cultures) for hPDCs cultured in osteogenic conditions. TEA maintained the integrity of fibrin-based constructs, with minor effects on the osteogenic differentiation of hPDCs.