This discussion and review article focuses on the possible use of regenerative techniques applied to the interfaces between skin and medical implants. As is widely known, the area of contact between an implant and the skin--the skin-implant interface--is prone to recurrent and persistent problems originated from the lack of integration between the material of the implant and the skin. Producing a long-term successful biointerface between skin and the implanted device is still an unsolved problem. These complications have prevented the development of advanced prosthetics and the evolution of biointegrated devices with new technologies. While previous techniques addressing these issues have relied mostly on the coating of the implants or the modification of the topology of the devices, recent in vitro developed techniques have shown that is possible to introduce biocompatible and possibly regenerative materials at the skin-device interface. These techniques have also shown that the process of delivering the materials has biological effects on the skin surrounding the implant, thus converting bioinert into bioactive, dynamic interfaces. Given that the best clinical outcome is the long-term stabilization and integration of the soft tissue around the implant, this article presents the basis for the selection of regenerative materials and therapies for long-term use at the skin-device interface, with focus on the use of natural biopolymers and skin cell transplantation.