Hydrothermal conversion of porous Ca carbonate biominerals into antibiotic and antiosteoporotic Ca phosphate bone implant materials containing Mg, Sr, Zn and Ag ions
Final Report Abstract
Annually, millions of bone graft procedures are performed for stabilizing and repairing bone defects. Synthetic materials based on calcium phosphate (CaP) are frequently used as bone graft substitutes where natural bone grafts are not available or not suitable. Chemical similarity to bone guarantees biocompatibility of synthetic CaP materials while macroporosity enables their integration into the natural bone tissue. To restore optimum mechanical performance after the grafting procedure, gradual resorption of CaP implants and simultaneous replacement by natural bone is desirable. Mg, Sr and Zn2+ ions released from resorbable implants support their osteointegration by stimulating bone formation. Furthermore, Sr ions counteract bone loss and reduce the probability of fractures as related to osteoporosis. During graft procedures, perisurgical wound infections are a major concern, since they retard wound healing and may cause implant failure. Hence, bioactive implant materials with antibacterial properties are highly desirable. Implants furnished with antibacterial Ag ions could help avoiding wound infections. This study aimed at developing porous calcium carbonate biominerals, namely coral skeletons and sea urchin spines, into novel CaP-based, bioactive and antimicrobial bone implant materials by a hydrothermal method to produce bone implant materials multi-functionalized by incorporating Mg2+, Sr2+, Zn2+ and Ag+ ions for stimulating bone formation and for antimicrobial properties. Pseudomorphic mineral replacement by a coupled dissolution/precipitation mechanism at the mineral/fluid interface was thought to allow for dissolved Mg 2+, Sr2+, Zn2+ and Ag+ ions, temporarily stabilized as EDTA complexes, to substitute for Ca2+ in the crystal lattice of the phosphate phases or to become incorporated at grain boundaries and/or grain surfaces. The major goal of producing bi- or multiphasic porous CaP materials doped with Mg2+ and Sr2+ ions through hydrothermal pseudomorphic replacement of Ca carbonate biominerals was achieved. Antibacterial modification of the resulting materials with Ag + ions was achieved as well. However, it was not possible to implement all additional ions in a single-step process of mineral conversion. Mg2+ and Ag2+ ions as EDTA complexes could not be held in the phosphate solution in sufficient amounts. Mg incorporation into CaP material was achieved by using Mgcalcite biominerals as starting materials (sea urchin spines) instead of Mg-free aragonite (coral skeletons). Ag2+ ions had to be added in a second process of mineral replacement of Ca/Mg/Sr phosphate in AgNO3 solution. The experimental work took considerably more time than expected so that the originally intended incorporation of Zn2+ ions into the CaP materials could not be accomplished. Macroporous skeletons of corals (aragonite) and sea urchins (Mg-calcite) were converted into pseudomorphic CaP materials with their natural porosity preserved. Coral skeletons were converted into carbonated hydroxyapatite [HA; approximately Ca9Na(PO4)5(CO3)(OH)2], while the major product phase from sea urchin spines was merrillite, Ca9MgNa(PO4)7. Sr ions were introduced to the mineral replacement reactions by temporarily stabilizing them in the hydrothermal sodium phosphate solutions as Sr-EDTA complexes. Upon modification of the coral-derived material with Sr, the major product phase was still HA with minor amounts of Srsubstituted ß-tricalcium phosphate, (Ca,Sr)3(PO4)2, while in the sea urchin-derived material, Srsubstituted merrillite was favoured over HA as the major product phase. An additional replacement reaction in Ag ion-containing solutions resulted in the formation of silver phosphate [Ag3(PO4)] nanoparticles at the surfaces of the Sr-modified CaP materials. Upon dissolution, the incorporated functional ions become released in biocompatible concentrations, endowing these CaP materials with antibacterial and potentially bioactive and antiosteoporotic properties. More research on these materials is needed, but the produced CaP scaffolds may turn out as novel osteoinductive, resorbable and antimicrobial bone implant materials and may offer alternative options to existing synthetic graft materials.
Publications
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(2018) Development of phosphatized calcium carbonate biominerals as bioactive bone graft substitute materials, part I: incorporation of magnesium and strontium ions. Journal of Functional Biomaterials 9 (4) 69
Sethmann I., Luft C., Kleebe H.-J.
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(2018) Development of phosphatized calcium carbonate biominerals as bioactive bone graft substitute materials, part II: functionalization with antibacterial silver ions. Journal of Functional Biomaterials 9 (4) 67
Sethmann I., Völkel S., Pfeifer F., Kleebe H.-J.
