Christian Bergmann

Calcium phosphate scaffolds mimicking the gradient architecture of native long bones

The synthesis of beta-tricalcium phosphate (β-TCP) scaffolds offering both the macroporous inner structure required for proper in vivo degradation and a non-macroporous outer structure for the enhancement of mechanical properties continues to be a challenge. The hypothesis of this study was to realize biomimetic β-TCP scaffolds with a macroporous inner structure and a compact outer structure using a lost wax casting technique. The porosity, macropore size, interconnectivity of the inner porous structure, and diameter of the outer compact structure were adjusted to specific values using a three-dimensional wax printer to manufacture the wax molds for the casting process. After the slip casting, the wax was pyrolyzed and the specimens were sintered. The resulting graded β-TCP scaffolds (porous + compact) were characterized and compared with β-TCP scaffolds with overall apparent macropores (only porous) and samples without macropores (only compact). The porosity and the compressive strength of the only compact, porous + compact, and only porous β-TCP samples were 31.4 ± 0.4 vol %, 55.6 ± 0.9 vol %, and 66.9 ± 0.4 vol % and 192 ± 7 MPa, 36 ± 2 MPa, and 9 ± 1 MPa, respectively. The macropore size was 500 µm and the micropore size was up to 10 µm, both featuring a completely open porous structure. From these results, we conclude that the lost wax casting technique offers an excellent method for the fabrication of β-TCP scaffolds with an inner macroporous structure and compact outer structure which mimics the cancellous and cortical structure of natural bone.

Calcium Phosphate Based Three-Dimensional Cold Plotted Bone Scaffolds for Critical Size Bone Defects

Bone substitutes, like calcium phosphate, are implemented more frequently in orthopaedic surgery to reconstruct critical size defects, since autograft often results in donor site morbidity and allograft can transmit diseases. A novel bone cement, based on β-tricalcium phosphate, polyethylene glycol, and trisodium citrate, was developed to allow the rapid manufacturing of scaffolds, by extrusion freeform fabrication, at room temperature. The cement composition exhibits good resorption properties and serves as a basis for customised (e.g., drug or growth factor loaded) scaffolds for critical size bone defects. In vitro toxicity tests confirmed proliferation and differentiation of ATDC5 cells in scaffold-conditioned culture medium. Implantation of scaffolds in the iliac wing of sheep showed bone remodelling throughout the defects, outperforming the empty defects on both mineral volume and density present in the defect after 12 weeks. Both scaffolds outperformed the autograft filled defects on mineral density, while the mineral volume present in the scaffold treated defects was at least equal to the mineral volume present in the autograft treated defects. We conclude that the formulated bone cement composition is suitable for scaffold production at room temperature and that the established scaffold material can serve as a basis for future bone substitutes to enhance de novo bone formation in critical size defects.

Impaired Fracture Healing after Hemorrhagic Shock

Impaired fracture healing can occur in severely injured patients with hemorrhagic shock due to decreased soft tissue perfusion after trauma. We investigated the effects of fracture healing in a standardized pressure controlled hemorrhagic shock model in mice, to test the hypothesis that bleeding is relevant in the bone healing response. Male C57/BL6 mice were subjected to a closed femoral shaft fracture stabilized by intramedullary nailing. One group was additionally subjected to pressure controlled hemorrhagic shock (HS, mean arterial pressure (MAP) of 35 mmHg for 90 minutes). Serum cytokines (IL-6, KC, MCP-1, and TNF-α) were analyzed 6 hours after shock. Fracture healing was assessed 21 days after fracture. Hemorrhagic shock is associated with a significant increase in serum inflammatory cytokines in the early phase. Histologic analysis demonstrated a significantly decreased number of osteoclasts, a decrease in bone quality, and more cartilage islands after hemorrhagic shock. μCT analysis showed a trend towards decreased bone tissue mineral density in the HS group. Mechanical testing revealed no difference in tensile failure. Our results suggest a delay in fracture healing after hemorrhagic shock. This may be due to significantly diminished osteoclast recruitment. The exact mechanisms should be studied further, particularly during earlier stages of fracture healing.

Calcium phosphate/microgel composites for 3D powderbed printing of ceramic materials

Abstract Composites of microgels and calcium phosphates are promising as drug delivery systems and basic components for bone substitute implants. In this study, we synthesized novel composite materials consisting of pure β-tricalcium phosphate and stimuli-responsive poly(N-vinylcaprolactam-co-acetoacetoxyethyl methacrylate-co-vinylimidazole) microgels. The chemical composition, thermal properties and morphology for obtained composites were extensively characterized by Fourier transform infrared, X-ray photoelectron spectroscopy, IGAsorp moisture sorption analyzer, thermogravimetric analysis, granulometric analysis, ESEM, energy dispersive X-ray spectroscopy and TEM. Mechanical properties of the composites were evaluated by ball-on-three-balls test to determine the biaxial strength. Furthermore, initial 3D powderbed-based printing tests were conducted with spray-dried composites and diluted 2-propanol as a binder to evaluate a new binding concept for β-tricalcium phosphate-based granulates. The printed ceramic bodies were characterized before and after a sintering step by ESEM. The hypothesis that the microgels act as polymer adhesive agents by efficient chemical interactions with the β-tricalcium phosphate particles was confirmed. The obtained composites can be used for the development of new scaffolds.

Preparation of spherical calcium phosphate granulates suitable for the biofunctionalization of active brazed titanium alloy coatings

Abstract Titanium-based alloys can be actively brazed onto bio-inert ceramics and potentially be used as biocompatible coatings. To further improve their bioactivity in vivo, introduction of calcium phosphate (CaP)-based granulates onto their surface layer is possible. For this, mechanically stable CaP-based granulates need to be able to withstand the demand of the brazing process. In this study, spherical granulates, made of a calcium phosphate composite composed primarily of β-tricalcium phosphate and hydroxyapatite, a bioactive glass, and a mixture of the previous two, were manufactured by spray drying. The influence of organic additives (Dolapix CE64, trisodium citrate) and solids content (30–80 wt%) in the slurry on the physical characteristics of granulates was investigated. X-ray diffraction, Brunauer, Emmett, Teller specific surface area standard method, scanning electron microscopy, granulate size analysis, and single granule strength were performed. Our results showed that trisodium citrate permitted the production of granulates with regular morphology, high density, and increased failure stress values. The strong granules also withstood the brazing process. These results show that CaP bioactive agents can be generated and be integrated during the demanding metallurgical processes, allowing for one-step bioactivation of metal brazes.

Ensuring defined porosity and pore size using ammonium hydrogen carbonate as porosification agent for calcium phosphate scaffolds

Abstract Up to now, it has been very challenging to manufacture a degradable bone replacement material having a specific pore size as well as a specific percentage of porosity which can be set independently of one another. We hypothesize that this is possible by using ammonium hydrogen carbonate (NH4HCO3) as porosification agent in varying particle size fractions and varying percentages in combination with β-tricalcium phosphate (β-TCP) material to manufacture tailored porous β-TCP scaffolds. In our study the pore sizes of the sintered material were comparable to the selected particle size fraction of the porosification agent. Porosities ranging between 71 and 78 vol.% were achieved. It was possible to control the volume percentage of porosity by using different weight ratios of NH4HCO3 and β-TCP. It can be concluded that ammonium hydrogen carbonate is an excellent porosification agent to design β-tricalcium phosphate scaffolds. This agent allows the independent setting of a specific pore size range as well as a specific volume percentage of porosity.