Biomedical Engineering Reference
In-Depth Information
markers of bone formation such as cbfa1, alkaline phosphatase, and type 1 b
collagen. At day 21, osteocalcin expression was also significantly upregulated
in an osteogenic medium. these results also suggested that exogenous Hyal
stimulates the synthesis of endogenous Hyal by the cells, thus playing a
synergetic role in osteogenic differentiation. at our knowledge, no reports
have shown the mineralisation potential of this biopolymer when incubated
in SBF
in vitro
.
Fibrin,
the product of polymerisation of fibrinogen, a plasma protein
responsible for blood clot formation, is another biopolymer widely used in
the biomedical field. The availability of commercial fibrin glues has been
exploited in tissue engineering as a matrix to encapsulate cells, among them
osteoblasts (Chow
et al
., 2008).
the inductive effect of the injectable osteoinductive material based on
fibrin sealant on the proliferation and differentiation of marrow stromal
cells (MSCs) towards osteoblasts has been demonstrated especially when in
combination with bone morphogenetic protein spiking (Cui
et al
., 2007a).
MSCs adhering to a fibrin substrate without any growth factor spiking showed
a lower degree of MSC differentiation toward osteoblasts and a higher
proliferation activity. This behaviour is consistent with the role of fibrin in
the early phases of tissue repair when cell proliferation is required.
Human MSC behaviour in eight different formulations of fibrin gels
(Tisseel™) prepared with various concentrations of fibrinogen complex and
thrombin varied, depending on the gel formulation (Malafaya
et al
., 2007).
In low fibrinogen complex concentration cell proliferation was reduced,
while alkaline phosphatase (aLP) activity increased in the formulations
containing a high concentration of this complex (Catelas
et al
., 2006). High
fibrinogen complex concentrations also induced the formation of small
mineralised bone noduli after 21 and 28 days of culture in hydrogel with
high fibrin concentration. This mineralisation process was concomitant with
an increase in the bone sialoprotein (BSP) gene expression level, and in
aLP and osteopontin levels, although to lesser extent. However, there was
no significant increase in the expression of osteocalcin, a late marker of
osteogenic differentiation. Therefore, human MSC differentiation in fibrin
gels seems to depend on the fibrinogen complex/thrombin ratio, although the
cells did not fully differentiate into mature osteoblasts. this cell behaviour
in fibrin matrices could be expected if it is considered that in a natural bone
repair process, fibrin intervenes in the very early phases of the repair in
response to bone fracture.
As fibrin is an ordered organic matrix which has a repeating periodic
structure of 230 Å, it could be expected to be a good substrate for Ha
formation. It has been demonstrated that HA crystallisation in fibrin gels
immersed in SBF is a very rapid process (Koutsopoulos and Dalas, 2000).
theoretical calculation seems to show that phosphate is taken up extensively
