## 4 Discussion  
The principal new finding of this study is the development of parameter-based numerical models for layered 3D-printed PCL scaffolds consisting of interconnected compartments. These in silico digital twins allow a fast, flexible and targeted scaffold design and production while conserving resources. 3D FEM models have been developed to describe the mechanical behavior of bone, cartilage and of scaffolds in BTE applications [29]. This is usually followed by creating 3D computer-aided design (CAD) models for 3D printing processes. The resulting datasets are commonly used as geometrical information for numerical FE simulations during preprocessing. Reversing that classical workflow, the use of parametric geometrical approaches allows us to widely vary these geometries to identify optimal structural shapes prior to fabrication. Such parametric geometrical numerical models are used in BTE applications, e.g., for describing human femur models [30], orthopedic implants [31] and the design of scaffolds [32]. Importantly, no parametric geometrical modeling studies for layered scaffolds based on PCL are available. So far, only a few FEM models for PCL have been reported. Those either focus on the influence of the unit cell, porosity and needle diameter [20] on the mechanical behavior, or the addition of calcium phosphates [33] or nanohydroxapatite to improve biocompatibility [34]. In these studies, the compressive strength of the entire layered scaffold was investigated. Here, we fabricated layered PCL scaffolds with interconnected compartments and developed for the first time geometrical parametric numerical models that determined the mechanical behavior of such scaffolds. The rationale for developing layered PCL scaffolds with interconnected compartments is their flexible properties and applications, despite their simple manufacturing method. Compartments can be filled with growth factors, hydrogels, fluids or drugs and enable three dimensionally connected cell growths [18; 19; 20; 21]. FEM is an established numerical approach that is used to determine forces, stresses and stains [16; 17]. Due to its compact geometry, the developed parameterized numerical models were implemented based on Beam188 Timoshenko elements. Comparative calculations with Strut-Elements and Euler-Bernoulli beams do not show considerable differences under  
Figure 9: Growth of Osteoblasts. Giemsa staining: chromatin—purple; L/D = Live/Dead Assay: Green—vital cells, red—dead cells. the chosen boundary conditions. This is due to the fact that the length-to-width ratio is at a border between the use of Timoshenko and Euler-Bernoulli theory. Furthermore, the pure tensile load of elements under the present boundary conditions leads to the classical tensile strut behavior of the model. The developed numerical model allows for the flexibility study of different geometries in silico to specifically plan the load testing of PCL scaffolds. This is particularly relevant for studies with osteoblasts, as they react specifically to mechanical stimulations [35, 36]. Furthermore, we demonstrated the successful development and additive fabrication of layered scaffolds based on PCL [11, 37, 38], but with specific architectures that included interconnected compartments. In a previous study, we demonstrated that variations in the architectural design of tissue-engineered constructs, combined with choosing specific biomaterial properties, can strongly influence the biomechanical performance of constructs. For example, the failure load of lamellar constructs can be increased by altering the lamellar width, number and order, and the increase reached such an extent that the failure loads of the individual materials used for construction were greatly exceeded [39]. In the present study, the architectures had 3D interconnected pores and slim strut thicknesses of about 150 \(\upmu\)m. The size of the pores and 3D connectivity play important roles to ensure sufficient nutrient transportation after in situ implantation [40, 41].