Bone regeneration in critical-size defects of the mandible using biomechanically adapted CAD/CAM hybrid scaffolds: An in vivo study in miniature pigs.

The study aimed to analyze bone regeneration in critical-size defects using hybrid scaffolds biomechanically adapted to the specific defect and adding the growth factor rhBMP-2. For this animal study, ten minipigs underwent bilateral defects in the corpus mandibulae and were subsequently treated with novel cylindrical hybrid scaffolds. These scaffolds were designed digitally to suit the biomechanical requirements of the mandibular defect, utilizing finite element analysis. The scaffolds comprised zirconium dioxide-tricalcium phosphate (ZrO2-TCP) support struts and TCP foam ceramics. One scaffold in each animal was loaded with rhBMP-2 (100 µg/cm³), while the other served as an unloaded negative control. Fluorescent dyes were administered every 2 weeks, and computed tomography (CT) scans were conducted every 4 weeks. Euthanasia was performed after 3 months, and samples were collected for examination using micro-CT and histological evaluation of both hard and soft tissue. Intravital CT examinations revealed minor changes in radiographic density from 4 to 12 weeks postoperatively. In the group treated with rhBMP-2, radiographic density shifted from 2513 ± 128 (mean ± SD) to 2606 ± 115 Hounsfield units (HU), while the group without rhBMP-2 showed a change from 2430 ± 131 to 2601 ± 67 HU. Prior to implantation, the radiological density of samples measured 1508 ± 30 mg HA/cm³, whereas post-mortem densities were 1346 ± 71 mg HA/cm³ in the rhBMP-2 group and 1282 ± 91 mg HA/cm³ in the control group (p = 0.045), as indicated by micro-CT measurements. The histological assessment demonstrated successful ossification in all specimens. The newly formed bone area proportion was significantly greater in the rhBMP-2 group (48 ± 10%) compared with the control group without rhBMP-2 (42 ± 9%, p = 0.03). The mean area proportion of remaining TCP foam was 23 ± 8% with rhBMP-2 and 24 ± 10% without rhBMP-2. Successful bone regeneration was accomplished by implanting hybrid scaffolds into critical-size mandibular defects. Loading these scaffolds with rhBMP-2 led to enhanced bone regeneration and a uniform distribution of new bone formation within the hybrid scaffolds. Further studies are required to determine the adaptability of hybrid scaffolds for larger and potentially segmental defects in the maxillofacial region.

3D bioprinting of mineralizing cyanobacteria as novel approach for the fabrication of living building materials.

Living building materials (LBM) are gaining interest in the field of sustainable alternative construction materials to reduce the significant impact of the construction industry on global CO2 emissions. This study investigated the process of three-dimensional bioprinting to create LBM incorporating the cyanobacterium Synechococcus sp. strain PCC 7002, which is capable of producing calcium carbonate (CaCO3) as a biocement. Rheology and printability of biomaterial inks based on alginate-methylcellulose hydrogels containing up to 50 wt% sea sand were examined. PCC 7002 was incorporated into the bioinks and cell viability and growth was characterized by fluorescence microscopy and chlorophyll extraction after the printing process. Biomineralization was induced in liquid culture and in the bioprinted LBM and observed by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and through mechanical characterization. Cell viability in the bioprinted scaffolds was confirmed over 14 days of cultivation, demonstrating that the cells were able to withstand shear stress and pressure during the extrusion process and remain viable in the immobilized state. CaCO3 mineralization of PCC 7002 was observed in both liquid culture and bioprinted LBM. In comparison to cell-free scaffolds, LBM containing live cyanobacteria had a higher compressive strength. Therefore, bioprinted LBM containing photosynthetically active, mineralizing microorganisms could be proved to be beneficial for designing environmentally friendly construction materials.

Tailoring of Hierarchical Porous Freeze Foam Structures.

Freeze foaming is a method to manufacture cellular ceramic scaffolds with a hierarchical porous structure. These so-called freeze foams are predestined for the use as bone replacement material because of their internal bone-like structure and biocompatibility. On the one hand, they consist of macrostructural foam cells which are formed by the expansion of gas inside the starting suspension. On the other hand, a porous microstructure inside the foam struts is formed during freezing and subsequent freeze drying of the foamed suspension. The aim of this work is to investigate for the first time the formation of macrostructure and microstructure separately depending on the composition of the suspension and the pressure reduction rate, by means of appropriate characterization methods for the different pore size ranges. Moreover, the foaming behavior itself was characterized by in-situ radiographical and computed tomography (CT) evaluation. As a result, it could be shown that it is possible to tune the macro- and microstructure separately with porosities of 49-74% related to the foam cells and 10-37% inside the struts.

Investigation of the Foam Development Stages by Non-Destructive Testing Technology Using the Freeze Foaming Process.

With a novel Freeze Foaming method, it is possible to manufacture porous cellular components whose structure and composition also enables them for application as artificial bones, among others. To tune the foam properties to our needs, we have to understand the principles of the foaming process and how the relevant process parameters and the foam's structure are linked. Using in situ analysis methods, like X-ray microcomputed tomography (µCT), the foam structure and its development can be observed and correlated to its properties. For this purpose, a device was designed at the Institute of Lightweight Engineering and Polymer Technology (ILK). Due to varying suspension temperature and the rate of pressure decrease it was possible to analyze the foam's developmental stages for the first time. After successfully identifying the mechanism of foam creation and cell structure formation, process routes for tailored foams can be developed in future.