The first step in the implementation of the OSTEOFIT project is the design of the printed matrix of the model for the creation of the composite implant (CI). As a model, a clinical file of 3D imaging method will be selected, for example: computed tomography (CT-Scan), derived from a bone deficiency area to establish the future connection of practices that will be developed with clinical research. UNISHAPE will undertake the creation of three-dimensional model and the design of the features of the, such as nutrient flow channels and stress transfer features.

In this computational model, there will be studied the nutrient flow with computer fluid dynamics (CFD) and the simulation of normal stresses with finite elements (FEM) based on mechanical properties described in the technical characteristics of biocompatible resins to be used. The results of FEM and CFD will be compared to the expected target values (shear and normal stresses) to the corresponding in vivo tissue, and if they do not coincide then, will follow a redesign loop. This model will be printed with biomaterials to create a high-resolution mold and will be evaluated for the actual flow field and stresses, as well as the in vitro biocompatibility. Finally, there will be publications of results of work in conferences. The bioreactor has the key role in the mechanical and biological maturation CI. The CI requires the proper time and the proper mechanical stimulation to mature, i.e. to begin the remodeling of the extracellular matrix material (extra cellular matrix, ECM) by the bio printed cells. KSA will undertake the design and the manufacture of the bioreactor which will be able to stream nutrient media through the CI and apply compressional forces. These procedures will be repeated in multiple circular loads for the CI samples. KSA will undertake both the mechanical design and the electronic setup (with appropriate subcontract) to allow the identification and the recording of the operating parameters. After the construction, all of the operation modes of the device will be tested.  BL will optimize the ratio of the bioink of the 3D bio printed bone tissue, cells, micro-and nano-structured particles of calcium phosphate (CaP particles) and additional components that will help in the clotting process in bio clay. The process will be enhanced by biofuctionalization with Bone Morphogenetic Protein (BMP). This cell-laden paste will be bioprinted within the 3D printed mold to create the CI. The CI will have the ideal morphology and the appropriate mechanical properties due to the high-resolution matrix, but also the CI will have a biologically active part with cells because of the bioprinting. The changes in the structure, and in the ratio of the biomaterial and cells as well as in the selection of biomaterials that will arise from the static in vitro assessments which will lead to the knowledge for a optimum formula. Also, the results will be published in relevant conferences.

The CI will undergo mechanical and biological maturation, under dynamic conditions with protocols which provide nutrient media, and cyclic compressive loads (e.g. 0.1% distortion, 1Hz, 4h/day for 15 days). This procedure is necessary to assess the degree of ECM remodeling from the same cells and eventually changes to mechanical features. After that, the biological response of the system will be evaluated. The affiliates will be able to take advantage of the expertise that they have gained from the project, as in their own benefit and in the society, through the dissemination of results at conferences.