One of the most common hereditary craniofacial anomalies in humans are cleft lip and cleft alveolar bone with or without cleft palate. Current clinical practice, the augmentation of the persisting alveolar bone defect by using autologous bone grafts, has considerable disadvantages motivating to an intensive search for alternatives. We developed a novel therapy concept based on 3D printing of biodegradable calcium phosphate-based materials and integration of osteogenic cells allowing fabrication of patient-specific, tissue-engineered bone grafts. Objective of the present study was the in vivo evaluation of implants in a rat alveolar cleft model. Scaffolds were designed according to the defect's geometry with two different pore designs (60 • and 30 • rotated layer orientation) and produced by extrusion-based 3D plotting of a pasty calcium phosphate cement. The scaffolds filled into the artificial bone defect in the palate of adult Lewis rats, showing a good support. Half of the scaffolds were colonized with rat mesenchymal stromal cells (rMSC) prior to implantation. After 6 and 12 weeks, remaining defect width and bone formation were quantified histologically and by microCT. The results revealed excellent osteoconductive properties of the scaffolds, a significant influence of the pore geometry (60 • > 30 •), but no enhanced defect healing by pre-colonization with rMSC.

Three dimensional (3D) printing allows additive manufacturing of patient specific scaffolds with varying pore size and geometry. Such porous scaffolds, made of 3D-printable bone-like calcium phosphate cement (CPC), are suitable for bone augmentation due to their benefit for osteogenesis. Their pores allow blood-, bone- and stem cells to migrate, colonize and finally integrate into the adjacent tissue. Furthermore, the pore size affects the scaffold’s stability. Since scaffolds in maxillofacial surgery have to withstand high forces within the jaw, adequate mechanical properties are of high clinical importance. Although many studies have investigated CPC for bone augmentation, the ideal porosity for specific indications has not been defined yet. We investigated 3D printed CPC cubes with increasing pore sizes and different printing orientations regarding cell migration and mechanical properties in comparison to commercially available bone substitutes. Furthermore, by investigating clinical cases, the scaffolds’ designs were adapted to resemble the in vivo conditions as accurately as possible. Our findings suggest that the pore size of CPC scaffolds for bone augmentation in maxillofacial surgery necessarily needs to be adapted to the surgical site. Scaffolds for sites that are not exposed to high forces, such as the sinus floor, should be printed with a pore size of 750 µm to benefit from enhanced cell infiltration. In contrast, for areas exposed to high pressures, such as the lateral mandible, scaffolds should be manufactured with a pore size of 490 µm to guarantee adequate cell migration and in order to withstand the high forces during the chewing process.

Reconstructing continuity defects of the mandible is still challenging for surgeons. The currently applied conventional titanium bridging plates have considerable rates of complications. Now, a new technology enables an individual shape-identical creation of a mandibular implant in a form-board design by the method of LaserCUSING using pure titanium. This technology has been successfully performed in previous examinations to individually reconstruct mandibular continuity defects. This pilot study evaluated the surgical procedure in 10 female Göttingen mini pigs. First, a computed tomography scan from a mini pig cranium was performed. A three-dimensional model of the mandible was designed by data conversion. Based on the data, a customized mandibular implant resembling the natural shape was virtually created and manufactured. Then, a continuity defect of the left mandible was created in a standardized way. The implants were inserted into the defect and the wounds were allowed to heal for 21, 35, 56 and 180 days. During the healing period, no signs of inflammation or infection were observed. After the sacrifice of the minipigs the mandibles were resected. Histological microsections using Donath's sawing and grinding technique were manufactured and stained with Masson Goldner trichrome staining. The histomorphological results showed a pronounced ossification at the outer and inner surface of the implants. This animal study describes a promising approach to optimize customized implants for the application in humans.

Magnetic resonance imaging (MRI) is a common clinical practice to visualize defects and to distinguish different tissue types and pathologies in the human body. So far, MRI data have not been used to model and generate a patient-specific design of multilayered tissue substitutes in the case of interfacial defects. For orthopedic cases that require highly individual surgical treatment, implant fabrication by additive manufacturing holds great potential. Extrusion-based techniques like 3D plotting allow the spatially defined application of several materials, as well as implementation of bioprinting strategies. With the example of a typical multi-zonal osteochondral defect in an osteochondritis dissecans (OCD) patient, this study aimed to close the technological gap between MRI analysis and the additive manufacturing process of an implant based on different biomaterial inks. A workflow was developed which covers the processing steps of MRI-based defect identification, segmentation, modeling, implant design adjustment, and implant generation. A model implant was fabricated based on two biomaterial inks with clinically relevant properties that would allow for bioprinting, the direct embedding of a patient’s own cells in the printing process. As demonstrated by the geometric compatibility of the designed and fabricated model implant in a stereolithography (SLA) model of lesioned femoral condyles, a novel versatile CAD/CAM workflow was successfully established that opens up new perspectives for the treatment of multi-zonal (osteochondral) defects. Graphic abstract

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