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 ā€“ 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. Ā 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 ā€œdual-settingā€ 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. Ā 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 Ā·2H2O) or struvite (MgNH4PO4 Ā·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.

Prof. Dr. rer. nat. Uwe Gbureck
Telephone +49(0)931 201-73550
uwe.gbureck@uni-wuerzburg.de

Dr. Juliane Kade
+49(0)931 31-89083
juliane.kade@uni-wuerzburg.de

M. Sc. Johannes Konrad
+49(0)931 201-73580
johannes.konrad@uni-wuerzburg.de

M. Sc. Paul Otto
+49(0)931 201-73554
paul.otto@uni-wuerzburg.de

Full list of colleagues

Seifert A, Groll J, Weichhold J, Boehm AV, MĆ¼ller FA, Gbureck U. Phase Conversion of Iceā€Templated Ī±ā€Tricalcium Phosphate Scaffolds into Lowā€Temperature Calcium Phosphates with Anisotropic Open Porosity. Adv. Eng. Mater. 2021; Accepted Author Manuscript.

Holzmeister I, Weichhold J, Groll J, Zreiqat,Gbureck, U. Hydraulic reactivity and cement formation of baghdadite. Journal of the American Ceramic Society.2021; Accepted Author Manuscript.

Kowalewicz K, Vorndran E, Feichtner F, Waselau A-C, Brueckner M, Meyer-Lindenberg A. In-Vivo Degradation Behavior and Osseointegration of 3D Powder-Printed Calcium Magnesium Phosphate Cement Scaffolds. Materials. 2021; 14(4):946.

Boehm AV, Meininger S, Gbureck U, Mueller FA. Self-healing capacity of fiber-reinforced calcium phosphate cements. Scientific Reports. 2020;10(1).

Wolf-Brandstetter C, Beutner R, Hess R, Bierbaum S, Wagner K, Scharnweber D, et al. Multifunctional calcium phosphate based coatings on titanium implants with integrated trace elements. Biomed Mater. 2020;15(2):025006.

Bruckner T, Fuchs A, Wistlich L, Hoess A, Nies B, Gbureck U. Prefabricated and Self-Setting Cement Laminates. Materials (Basel). 2019;12(5).

Weichhold J, Gbureck U, Goetz-Neunhoeffer F, Hurle K. Setting Mechanism of a CDHA Forming alpha-TCP Cement Modified with Sodium Phytate for Improved Injectability. Materials (Basel). 2019;12(13):2098.

Ewald A, Kreczy D, Bruckner T, Gbureck U, Bengel M, Hoess A, et al. Development and Bone Regeneration Capacity of Premixed Magnesium Phosphate Cement Pastes. Materials (Basel). 2019;12(13).

Charbonnier B, Baradaran A, Sato D, Alghamdi O, Zhang Z, Zhang YL, et al. Material-Induced Venosome-Supported Bone Tubes. Adv Sci (Weinh). 2019;6(17):1900844.

Hettich G, Schierjott RA, Epple M, Gbureck U, Heinemann S, Mozaffari-Jovein H, et al. Calcium Phosphate Bone Graft Substitutes with High Mechanical Load Capacity and High Degree of Interconnecting Porosity. Materials (Basel). 2019;12(21).

Bruckner T, Meininger M, Groll J, Kubler AC, Gbureck U. Magnesium Phosphate Cement as Mineral Bone Adhesive. Materials (Basel). 2019;12(23).

Roedel M, Tessmar J, Groll J, Gbureck U. Tough and Elastic alpha-Tricalcium Phosphate Cement Composites with Degradable PEG-Based Cross-Linker. Materials. 2019;12(1).