Barbieri Thesis - BioMedical Materials program (BMM)

Chapter 2 – The role of gels in instructive putties
may inhibit or slow down the (stem) cell adhesion, proliferation and osteogenic
differentiation onto BCP granules. Although several polymer gels inhibit or limit bone
formation in the putties, we have shown that certain biocompatible gels with fast
dissolution rate (i.e. CMC and PLU gels) allow inductive bone formation in similar
volume as the control (i.e. loose BCP granules). These results show that it is possible
to develop osteoinductive putties for bone repair. However, it should be observed that
five gels with various chemistries and putties having different gel/BCP volume ratios
have been used in this study. Therefore, to ensure that the gel dissolution rate is the
key factor controlling bone induction in these composite materials, future experiments
should focus on one gel chemistry with varying dissolution rates. It would be useful to
implant the materials in orthotopic sites to evaluate their clinical potential. Further,
analysing the temporal evolution of bone formation, both in heterotopic and orthotopic
sites, by using multiple time points during the animal studies would provide useful
information to better understand the biology of bone formation induced by such
biomaterials and the role played by the gel component.
Further, it should be mentioned that the carriers used in this study, similarly to others
reported in literature, [292, 293] were water–based. The prolonged contact of calcium
phosphate ceramics, including those slowly dissolvable, with such aqueous gels will
eventually lead to their hydrolysis changing their surface topographical structure and
chemistry. [292, 294] Since water–based gels contain high content of water (i.e. 60 to
95%wt., Table 2) we recently performed an accelerated aging test based on the
approach (derived from Arrhenius relation) assuming that the rate of aging is
increased by a factor [368]
f = 2 (T – Tref )/10
where Tref is the temperature at which the effects of aging are to be determined and T
is an elevated temperature used to accelerate these effects. [353, 368] The factor f
indicates how many months at Tref are equivalent to aging the material at T for one
month. The condition to apply this factor is that the (accelerated) aging temperature T
should be (sufficiently) lower than the temperature at which the tested material
distorts. [368] In general, such temperature T should be 5 to 10°C less than any major
thermal transition. [368] For example, in the case of medical devices comprising
polymers it is suggested that T should be not higher than 60°C as above it non–linear
changes would occur in many polymer systems. [353–357, 368] Calcium phosphate
ceramics are thermally instable for temperatures higher than 850°C, [369–370] thus we
could apply the above equation with Tref=20°C and T=50°C. In this way, keeping the
granules at 50°C for one month corresponds to aging them at 20°C for 8 months. So,
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