Transformative Materials to Create 3D Functional Human Tissue Models In Vitro in a Reproducible Manner.

Recreating human tissues and organs in the petri dish to establish models as tools in biomedical sciences has gained momentum. These models can provide insight into mechanisms of human physiology, disease onset, and progression, and improve drug target validation, as well as the development of new medical therapeutics. Transformative materials play an important role in this evolution, as they can be programmed to direct cell behavior and fate by controlling the activity of bioactive molecules and material properties. Using nature as an inspiration, scientists are creating materials that incorporate specific biological processes observed during human organogenesis and tissue regeneration. This article presents the reader with state-of-the-art developments in the field of in vitro tissue engineering and the challenges related to the design, production, and translation of these transformative materials. Advances regarding (stem) cell sources, expansion, and differentiation, and how novel responsive materials, automated and large-scale fabrication processes, culture conditions, in situ monitoring systems, and computer simulations are required to create functional human tissue models that are relevant and efficient for drug discovery, are described. This paper illustrates how these different technologies need to converge to generate in vitro life-like human tissue models that provide a platform to answer health-based scientific questions.

Femoral strain changes after total hip arthroplasty--patient-specific finite element analyses 12 years after operation.

Periprosthetic stress-shielding after total hip arthroplasty (THA) is a well-known phenomenon. Many authors have used the finite element (FE) method to show the effects of THA on animal or human femora. In most cases they have performed cadaver experiments. The current project is a FE analysis based on a retrospective computerized tomography (CT) in vivo data set of 11 patients 12 years after THA. In order to control the analysis, a computationally created stem was implanted at the femur model of the not operated contralateral side. In comparison to the not operated side, there was a significant reduction of the strain energy density (SED) values in all regions of interest (ROI) with the greatest effect near the distal tip of the stem. Only zone 1 showed no clear trend which may be due to load application at the greater trochanter causing local strain peaks. The median SED values changed by -31.65% (ROI 1), -25.64% (ROI 2), -30.82% (ROI 3), -12.35% (ROI 4), -40.10% (ROI 5), -30.37% (ROI 6) and -43.38% (ROI 7). As far as we are aware, the current combination of in vivo CT density data with FE strain analyses after THA is based on the largest number of patients and the longest follow-up period. This combination enables analysis and prediction of the influence of implantation upon bone and can be compared with of remodelling theories. The assessment of mechanical strain data during a follow-up trial could be a new approach for analyzing different hip stems in clinical biomechanics.