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Long-term studies in the non-human primate Chacma baboon Papio ursinus were set to investigate the induction of bone formation by biphasic hydroxyapatite/p-tricalcium phosphate (HA/beta-TCP) biomimetic matrices. HA/beta-TCP biomimetic matrices in a pre-sinter ratio (wt%) of 40/60 and 20/80, respectively, were sintered and implanted in the rectus abdominis and in calvarial defects of four adult baboons. The post-sinter phase content ratios were 19/81 and 4/96, respectively. Morphological analyses on day 90 and 365 showed significant induction of bone formation within concavities of the biomimetic matrices with substantial bone formation by induction and resorption/dissolution of the implanted matrices. One year after implantation in calvarial defects, 4/96 biphasic biomimetic constructs showed prominent induction of bone formation with significant dissolution of the implanted scaffolds. The implanted smart biomimetic matrices induce de novo bone formation even in the absence of exogenously applied osteogenic proteins of the transforming growth factor-beta(TGF-beta) superfamily. The induction of bone formation biomimetizes the remodelling cycle of the cortico-cancellous bone of primates whereby resorption lacunae, pits and concavities cut by osteoclastogenesis are regulators of bone formation by induction. The concavities assembled in HA/beta-TCP biomimetic bioceramics are endowed with multifunctional pleiotropic self-assembly capacities initiating and promoting angiogenesis and bone formation by induction. Resident mesenchymal cells differentiate into osteoblastic cell lines expressing, secreting and embedding osteogenic soluble molecular signals of the TGF-beta superfamily within the concavities of the biomimetic matrices initiating bone formation as a secondary response.

Biphasic calcium phosphate ceramics (BCP) comprising a mix of non-resorbable hydroxyapatite (HA) and resorbable beta-tricalcium phosphate (beta-TCP) are particularly suitable materials for synthetic bone substitute applications. In this study, HA synthesised by solid state reaction was mechanically mixed with beta-TCP, then sintered to form a suite of BCP materials with a wide range of HA/beta-TCP phase content ratios. The influence of sintering temperature and composition on the HA thermal stability was quantified by X-ray diffraction (XRD). The pre-sinter beta-TCP content was found to strongly affect the post-sinter HA/beta-TCP ratio by promoting the thermal decomposition of HA to beta-TCP, even at sintering temperatures as low as 850 degrees C. For BCP material with pre-sinter HA/beta-TCP = 40/60 wt%, approximately 80% of the HA decomposed to beta-TCP during sintering at 1000 degrees C. Furthermore, the HA content appeared to influence the reverse transformation of alpha-TCP to beta-TCP expected upon gradual cooling from sintering temperatures greater than 1125 degrees C. Because the HA/beta-TCP ratio dominantly determines the rate and extent of BCP resorption in vivo, the possible thermal decomposition of HA during BCP synthesis must be considered, particularly if high temperature treatments are involved.

Background: The authors investigated in nonhuman primates (Papio ursinus) whether it is possible to engineer biomimetic matrices that induce the differentiation of osteoblastic cells expressing selected osteogenic mRNA species of the transforming growth factor (TGF)-beta superfamily., Methods: Four types of sintered hydroxyapatite and biphasic hydroxyapatite/tricalcium phosphate bioceramics were evaluated as osteoinductive self-inducing biomimetic matrices. Matrices were fabricated with a series of repetitive concavities that initiate the induction of bone formation as a secondary response. Single-phase hydroxyapatite, biphasic hydroxyapatite/tricalcium phosphate, and carbon-impregnated single-phase hydroxyapatite, the latter with fine and coarse porosities, were implanted heterotopically in the rectus abdominis. Specimens for orthotopic calvarial implantation were a total of 16 macroporous disks 25 mm in diameter of single-phase hydroxyapatite and biphasic hydroxyapatite/tricalcium phosphate., Results: Heterotopic specimens 90 and 180 days after implantation showed the induction of bone within concavities of the biomimetic matrices. Northern blot analyses of heterotopic specimens showed that carbon-impregnated single-phase hydroxyapatite specimens induced high expression of osteogenic protein-1 mRNA, correlating with the induction of bone formation. Collagen type IV mRNA was highly expressed, particularly on day 90, by all the implanted matrices. Orthotopic specimens showed substantial bone formation across the implanted constructs., Conclusions: Self-induced bone has been achieved via the deployment of osteogenic molecular signals expressed by differentiating osteoblastic-like cells, later secreted and embedded into the smart concavities of the biomimetic matrices. The described biomimetic matrices induce de novo bone formation even in the absence of exogenously applied osteogenic proteins of the TGF-beta superfamily.

In piston-cylinder studies of reconstructive phase transitions, piston rotation plays a more subtle role than has previously been thought. Rotation of the piston not only relieves sliding friction, but also helps to activate sluggish transformations. This suggests modification of the traditionally accepted volumetric technique, and of the standard interpretation of data.