Self-inducing shape memory geometric cues embedded within smart hydroxyapatite-based biomimetic matrices.

Abstract

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. 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. 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. 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.