One of the greatest challenges in the development of new medical devices remains in providing maximal patient safety, efficacy and suitability for the purpose. A "good quality" of the tissue‐implant interface is one of the most critical factors for the success of the implant integration. For many clinical applications mechanobiology and associated phenomena are of very high importance but they often remain overlooked. In this work the key aspects of mechanobiology of biomaterials and implants are highlighted, from sub‐cellular level to clinical translation, complemented with a brief overview of new medical devices regulations (2017/745) and testing challenges. This also combined with the modern trends of personalized medicine (here as “personalized biomaterials”) and the individual risk assessment of a biomaterial for a particular patient. Also the requirements of reduction, refinement and replacement (3R) of animal tests (2010/63/EC) are considered. Some recent examples are also briefly introduced.