*4.1. Limitations of the Study*

The authors would like to point out that the study, in its present form, is mainly theoretical and simply aims to present a set of CAD and FEM resources for a more straightforward personalization and in silico evaluation of short stem hip prostheses. Furthermore, the printed prototypes are merely conceptual test probes, in no case intended to be implanted or in vivo tested yet. Several improvements should be performed before considering the proposed designs viable, and the final manufacturing technologies would be completely different to those employed here for a preliminary evaluation of implantability. Probably, for a hypothetical personalized implant with a design such as those presented here, additive manufacturing of metallic alloys (selective laser sintering/melting) would be a good choice, as well as lithography-based ceramic manufacturing using biomedical ceramics, although, in all cases, a final postprocess (sand blasting, PVD-CVD coating) would be beneficial for

enhancing osseointegration. The 3D printing of conceptual prototypes helped to initially assess implantability, although design improvements should of course require medical support. In fact, according to the EU Medical Device Regulation 2017/745 (and to most medical regulations worldwide), customized implants cannot reach patients without the prescription and implication in the design procedure of physicians and surgeons. This study provides the basic point of view of biomechanical engineers.

Collaboration with surgeons would be fundamental for improving the design and for considering challenging issues that can be encountered in real-life surgery, including: (1) the need for rasping and for personalized rasps, which could be designed by downscaling the personalized implants and printing both the customized implants and the supporting tools; (2) the occurrence of unexpected collisions during surgery, which could be alleviated by printing two or three models of the customized design, with slightly different surface finishes or scales, and (3) the potential contraindications when abnormal morphologies are present. In the authors' opinion, contraindications for the proposed customized designs would be similar to those applicable to short stems in general: presence of hip dysplasia, severe osteoporosis and previous hip osteotomies.

In any case, before the presented designs can be considered successful solutions, systematic in vitro and in vivo evaluations (with test benches and animal models following the three R principles and applicable regulations) guided by physicians and surgeons are needed.
