High Toughness Biocompatible Resorbable Bone Cements

Bone substitutes need to be tough and bioresorbable in many clinical applications, especially in load-bearing areas. However, the available biomaterials are either too brittle or do not resorb upon implantation, which a critical characteristic for optimal bone regeneration. Accordingly, the goal of this thesis is to create high -toughness biocompatible bone substitutes w ith a resorption rate matching bone formation rate. Calcium – phosphates dihydrate (brushite) and calcium sulfate dihydrate (gypsum) are very promising bone substitute biomaterials because of their high calcium content, biocompatibility, and bioresorbabilit y. However, the incompatible resorption rate and brittleness of these materials limit their use, especially in load-bearing areas. Unlike brittle synthetic bone cements/ ceramics, natural biominerals such as bone and teeth have remarkable mechanical prop erties resulting from the controlled size, shape, and organization of their inorganic crystals. This is achieved by biomineralization proteins that are homochiral, composed of L-amino acids. In addition to crystal structure organization, the toughening mechanisms in these biological mineralized tissues include promoting crack deflection and grain bridging also achieved through the action of organic fibers, such as mineralized collagen. In this thesis, we hypothesized that tough, resorbable bone cements could be produced using a biomimetic approach in which the crystallographic structure of inorganic cements is controlled by chiral biomolecules and reinforced with functionalized organic fibers. In the first study, we assessed the impact of chiral biomolecules on the crystal structure and the mechanical properties of brushite cements. We show that the addition of homochiral L-(+)-tartaric acid improved the mechanical properties of brushite cements by decreasing their crystal size, following the classic Hall -Petch strengthening effect; D-(-)-tartaric acid had the opposite effect. Characterization of brushite crystals from the macro – to the atomic -level revealed that this regulation is attributable to a stereochemical matching between L-(+)-tartaric acid and the c hiral steps of brushite crystals, which results in inhibition of brushite crystallization. In the second study, we studied the effect of various chiral α -hydroxycarboxylic acids on the properties of gypsum cements. This study demonstrates that chiral L-(+)-hydroxycarboxylic acids can effectively improve the mechanical properties of gypsum cements by controlling crystal size and morphology. In contrast, D-enantiomer had a weak effect. Thus, these results prove the generalizability of this approach and help to fabricate high strength cements. These results could also help develop mechanically strong biomaterials and shed light on the role of chiral molecules in the biomineralization process. In the third study, we used chiral biomolecules to develop brushite -gypsum composites with optimized mechanical properties and resorption rates and reinforcing them with resorbable functionalized polyglactin fibers. By combining brushite and gypsum, we were able to fabricate biocompatible composite with high fracture toughness, and a resorption rate that matched the rate of new bone formation. Adding functionalized polyglactin fibers to this composite cement further improved the fracture toughness of this composites. XPS and SEM revealed that the improvement in fracture to ughness is attributed to the strong interfacial bonding between the functionalized fibers and the cement matrix . This study showed that a dding gypsum and functionalized polyglactin fibers to brushite cements result in composite biomaterials that combine hi gh fracture toughness, resorbability, and biocompatibility, and have great potential for bone regeneration.