The aim of this study is to explore, with an in vivo model, the regeneration of articular cartilage that can be obtained with a strategy that combines the stimulation of the subchondral bone with the implantation of a biomimetic microgel at the site of the cartilage defect. The microgel consists of an agglomerate of two types of microspheres: ones rigid, made of a biodegradable polyester, and the other ones composed of a polymeric network of gelatin and hyaluronic acid that encapsulate platelet-rich plasma (PRP) obtained from circulating autologous blood. A defect of 7 mm in diameter and full depth was performed in the in the articular cartilage at the trochlea of the animal knee, using a minipig model. Microdrilling was performed in the underlying bone and the defect was filled with the microgel in which the platelets it contains were previously activated with calcium chloride. The whole defect containing the microgel was covered with a synthetic membrane to avoid the release of microspheres. The results of the in vivo follow-up of the experiment, the histological analysis and the mechanical measurements of the regenerated tissue 9 months after implantation were compared with those of a group of animals in which only microdrilling was performed and the defect was covered with the membrane and with another group in which a clinical use commercial collagen mesh was implanted. The mean value of the elastic modulus of the newly formed tissue was not significantly different from that of the native tissue in the case of microgel implantation while its content of GAGs, was significantly better than in the other groups.