Bioactive Inorganic Scaffolds

The development of inorganic scaffold materials for bone regeneration at FMZ is based on reactive calcium- and magnesium phosphates (CaP and MgP) that set after addition of water under ambient conditions by a dissolution – precipitation reaction. Primary aims are focused on the synthesis and reactivity of the powders, their rheological optimization for injectability, the biological behavior in vitro and in vivo, and the mechanical strength of the resulting ceramics.  A current development concerns bioceramics and cements based on magnesium phosphate chemistry. The rationale behind this is the good solubility of MgP phases under in vivo conditions and the fact that Mg2+ is a potent inhibitor of hydroxyapatite crystal growth thereby suppressing unwanted crystallization in vivo. In contrast to implants made of magnesium metal, magnesium phosphate ceramics and cements do not produce hydrogen gas and an alkaline environment during dissolution.

Mechanical reinforcement of mineral bone cements

Main strategies followed at FMZ to improve the typical brittle fracture behavior of bioceramics and cements are the integration of reinforcing fibers or by using a “dual-setting” approach. The latter is based on a simultaneous formation of a second hydrogel matrix within the cement to overcome the typical brittle behavior of the cement.  Here, reactive monomer systems are dissolved in the cement liquid and rapidly polymerized during setting by internal or external stimuli. This forms a hydrogel matrix with embedded cement particles, which are subsequently converted into the setting product to form interpenetrating hydrogel-cement composites. The advantages of this approach compared to simply adding dissolved polymers are the possibility of a higher polymer loading of the cement (and hence a large strength and toughness increase) as well as practically unchanged viscosity of the fresh cement paste. This concept was applied to a couple of different polymers such as Poly-hydroxyethylmethacrylate (poly-HEMA), silk fibroin or isocyanate functionalized star-PEGs leading to a strong reduction of cement brittleness and hence improved fracture behavior.

Additive manufacturing of bone scaffolds

Cement powders are also used for rapid-prototyping by 3D printing techniques for the construction of individualized geometries with a high lateral resolution (Figure left) and precisely defined macropores for blood vessel ingrowth (Figure right). The advantage of using cements for 3D printing is a processing regime at low temperature, which allows the fabrication of hydrated, secondary phosphates such as brushite (CaHPO4 ·2H2O) or struvite (MgNH4PO4 ·6H2O), which are more soluble than commonly used hydroxyapatite or tricalcium phosphate ceramics. In addition, the use of multi-colour printers allows the local deposition of bioactives in the 3D scaffolds during printing for a spatial control of tissue response and drug release kinetics.

Example of a 3D powder printed bioceramic implant

X-ray micrograph of a 3D printed porous network in a bioceramic structure

Surface modification of implant metals

The biocompatibility especially of non-degradable implant materials arises from its surface. Electrochemically assisted deposition is used to equip metallic surfaces with low-crystalline calcium and magnesium phosphate coatings. One aim of these studies is the development of novel multi-phase coatings with incorporated ions, which combine bactericidal and bioactive properties and hence can decrease the risk of inflammation after surgery and support the subsequent in-growth of the medical implant. Another strategy for increasing the lifetime of orthopedic implants is the deposition of hard coatings by physical vapor deposition (PVD). Here, refractory metal (Ti, Zr, Ta) oxides and nitrides are used, which can be further modified by silver ions for antimicrobial properties.

Dr. rer. nat. Elke Vorndran
3D powder printing of calcium and magnesium phosphate cement systems and drug delivery systems
+49(0)931-31 89083
elke.vorndran@fmz.uni-wuerzburg.de
Photo | Research | CV

M. Sc. Ib Holzmeister
Multifunctional precursors for improved bioceramic systems
+49(0)931 201-73554
ib.holzmeister@fmz.uni-wuerzburg.de

M. Sc. Jan Weichhold
Manipulation of biocement setting by functional additives
+49(0)931 201-73554
jan.weichhold@fmz.uni-wuerzburg.de

Full list of colleagues

I. Holzmeister, M. Schamel, J. Groll, U. Gbureck, E. Vorndran, Artificial inorganic biohybrids: The functional combination of microorganisms and cells with inorganic materials, Acta Biomaterialia  74 (2018) 17-35.

M. Rodel, J. Tessmar, J. Groll, U. Gbureck, Highly flexible and degradable dual setting systems based on PEG-hydrogels and brushite cement, Acta biomaterialia  (2018).

M. Nabiyouni, T. Brueckner, H. Zhou, U. Gbureck, S.B. Bhaduri, Magnesium-based bioceramics in orthopedic applications, Acta Biomaterialia 66 (2018) 23-43.

T. Brueckner, K. Hurle, A. Stengele, J. Groll, U. Gbureck, Mechanical activation and cement formation of trimagnesium phosphate, Journal of the American Ceramic Society 101 (2018) 1830-1834.

M. Schamel, J.E. Barralet, M. Gelinsky, J. Groll, U. Gbureck, Intrinsic 3D Prestressing: A New Route for Increasing Strength and Improving Toughness of Hybrid Inorganic Biocements, Advanced Materials 29 (2017) 1701035.

S. Meininger, C. Blum, M. Schamel, J.E. Barralet, A. Ignatius, U. Gbureck, Phytic acid as alternative setting retarder enhanced biological performance of dicalcium phosphate cement in vitro, Scientific  Reports 7 (2017).

C. Blum, T. Bruckner, A. Ewald, A. Ignatius, U. Gbureck, Mg:Ca ratio as regulating factor for osteoclastic in vitro resorption of struvite biocements, Material Science & Engineering C 73 (2017) 111-119.

S. Meininger, S. Mandal, A. Kumar, J. Groll, B. Basu, U. Gbureck, Strength reliability and in vitro degradation of three-dimensional powder printed strontium-substituted magnesium phosphate scaffolds, Acta Biomaterialia 31 (2016) 401-411.

M. Meininger, C. Wolf-Brandstetter, J. Zerweck, F. Wenninger, U. Gbureck, J. Groll, C. Moseke, Electrochemically assisted deposition of strontium modified magnesium phosphate on titanium surfaces, Materials Science & Engineering C 67 (2016) 65-71.

T. Bruckner, M. Schamel, A.C. Kubler, J. Groll, U. Gbureck, Novel bone wax based on poly(ethylene glycol)-calcium phosphate cement mixtures, Acta Biomaterialia 33 (2016) 252-63.

E. Vorndran, C. Moseke, U. Gbureck, 3D printing of ceramic implants, MRS Bulletin 40 (2015) 127-136.

M. Geffers, J. Groll, U. Gbureck, Reinforcement Strategies for Load-Bearing Calcium Phosphate Biocements, Materials 8 (2015) 2700-2717.

T. Christel, S. Christ, J.E. Barralet, J. Groll, U. Gbureck, Chelate Bonding Mechanism in a Novel Magnesium Phosphate Bone Cement, Journal of the American Ceramic Society 98 (2015) 694-697.

B. Kanter, M. Geffers, A. Ignatius, U. Gbureck, Control of in vivo mineral bone cement degradation, Acta Biomaterialia 10 (2014) 3279-3287.

E. Vorndran, M. Geffers, A. Ewald, M. Lemm, B. Nies, U. Gbureck, Ready-to-use injectable calcium phosphate bone cement paste as drug carrier, Acta Biomaterialia 9 (2013) 9558-9567.

A. Ewald, D. Hosel, S. Patel, L.M. Grover, J.E. Barralet, U. Gbureck, Silver-doped calcium phosphate cements with antimicrobial activity, Acta Biomaterialia 7 (2011) 4064-4070.

E. Vorndran, U. Klammert, A. Ewald, J.E. Barralet, U. Gbureck, Simultaneous Immobilization of Bioactives During 3D Powder Printing of Bioceramic Drug-Release Matrices, Advanced Functional Materials 20 (2010) 1585-1591.

C. Grossardt, A. Ewald, L.M. Grover, J.E. Barralet, U. Gbureck, Passive and Active In Vitro Resorption of Calcium and Magnesium Phosphate Cements by Osteoclastic Cells, Tissue Engineering Part A 16 (2010) 3687-3695.

M.H. Alkhraisat, C. Moseke, L. Blanco, J.E. Barralet, E. Lopez-Carbacos, U. Gbureck, Strontium modified biocements with zero order release kinetics, Biomaterials 29 (2008) 4691-4697.

U. Gbureck, T. Hozel, U. Klammert, K. Wurzler, F.A. Muller, J.E. Barralet, Resorbable dicalcium phosphate bone substitutes prepared by 3D powder printing, Advanced Functional Materials 17 (2007) 3940-3945.