2. Process chain for the production of therapeutic unique products

The existing process chain without considering the biomechanical simulation includes the image acquisition, the image post-processing and the rapid prototyping [4, 5]. The image raw data acquired using CT or MRI are segmented, visualized and transferred in a suitable data format by image post-processing. In the next step, a computer-aided design (CAD) model of the segmented objects is generated. Finally, these CAD data can be used to create a customized implant design [6]. This process chain can be expanded by biomechanical simulations to determine the patient-specific stress situation in spinal structures preoperatively. Based on this simulation, a patient-specific implant with an optimal fitting can be designed to reduce the risk of complications, incorrect loading conditions due to insufficient adapted implant design and adjacent segment degeneration. A possible expanded process chain could look like Figure 1, based on Hüsing et al. [1] and Rengier et al. [3].

The expanded process chain starts with the medical imaging or technical construction as the basis for the following three-dimensional (3D) reconstruction. After the three-dimensional reconstruction of the data, a biomechanical simulation model can be created. In a simulation model, morphological information and biomechanical properties of the patent-specific spine as well as of the corresponding implant are obtained. The aim of this biomechanical simulation is to ensure a "natural" stress distribution on the various spinal structures by the modeling of a patient-specific implant. Thus, overloading, which can lead to degenerative damage to the

Figure 1. Expanded process chain with implemented biomechanical modeling.

head, should be avoided. This aim can be achieved by optimized positioning of the implant, an optimization of the implant design as well as of the implant material properties.

The goal of finding an optimal positioning (1) of an implant is in focus, which ensures, for example, a "natural" stress distribution, can be determined by the patient-specific simulation model. If desired, the exact coordinates of the positioned implant can be exported. These can then be taken into account in the operation planning. The rapid prototyping can be realized sequentially or in parallel.

If the baseplate design of a "standardized" implant is not suited to the morphological conditions of the contact surface of a patient-specific vertebral body, alternative baseplate designs can be demonstrated by means of a biomechanical simulation. In addition, corresponding modifications in implant material properties can also be analyzed and its effect on the spinal structures can be evaluated (see Figure 1 process chain, loop (2a)). Thus, the risk of complications is minimized through, for example, an insufficient anchoring and the concomitant loosening of the implant or the occurrence of load peaks by point contact. On the basis of the simulation results, the implant can be re-designed specifically for a patient (see Figure 1 process chain, loop (2b)), and corresponding input data (see Figure 1 process chain, loop (2c)) can be generated for the further processing of rapid prototyping.

In the field of rapid prototyping, generative creations and processes with material removal can be different. Generative creation is the production of 3D physical models by applying material in thin layers and solidifying them. Established techniques are stereolithography, selective laser sintering, fused deposition modeling, laminated object manufacturing, and inkjet-printing techniques. A more detailed explanation can be taken from [3].

With such an expanded process chain, patient-specific implants can be produced not only with optimally shaped contact surfaces, which ensure a permanent fit of the implant without sinking and slipping, but also preoperative predictions can be made about the biomechanical effects of the implant and an optimized positioning can be proposed.
