Fractures, especially if articular and periarticular, are frequently associated to functional and clinical disabling outcomes and chronic pain. In particular, the injuries with loss of bone, ligament, and/or tendon tissue in which the full recovery of the wound area is not obtained are the worst anatomical/pathological conditions to heal. In this study, three different biological materials were used as regenerative approaches to rebuild the medial malleolus fracture of the ankle in which loss of bone, ligament, and tendon tissue occur. In particular, the morselized human bone tissue was combined with the human dermis decellularized, both augmented with homologous platelet-rich plasma. The magnetic resonance imaging study with contrast at the follow-up showed a signal compatible with vascularization of the tissue without sign of degeneration. Our new regenerative approach in which different biological materials were combined together showed a good choice of treatment for the reconstruction of not repairable outcome of a fracture.