Duchenne muscular dystrophy (DMD) is caused by the lack of dystrophin; affected muscles are characterized by continuous bouts of muscle degeneration, eventually leading to the exhaustion of the endogenous satellite cell pool. At present, only palliative treatments are available, although several gene and cell therapy-based approaches are being studied. In this study we proposed to overcome the limitations hampering intramuscular cell injection by using a biomaterial-based strategy. In particular, we used a three-dimensional (3D) collagen porous scaffold to deliver myogenic precursor cells (MPCs) in vivo in the mdx murine model of DMD. MPCs, derived from single fibres of wild-type donors, were expanded in vitro, seeded onto collagen scaffolds and implanted into the tibialis anterior muscles of normal and mdx mice. As a control, cells were delivered via direct intramuscular cell injection in the contralateral muscles. Scaffold-delivered MPCs displayed lower apoptosis and higher proliferation than injected cells; in terms of dystrophin restoration, collagen scaffolds yielded better results than direct injections. Importantly, time-course experiments indicated that the scaffolds acted as a cell reservoir, although cell migration was mostly contained within 400 µm from the scaffold-host tissue interface.