The clinical translation of regenerative therapies, whether in the form of mesenchymal cells, macromolecules or small molecules, is hampered by several factors: the poor retention and short biological half-life of the therapeutic agent, the adverse side effects from systemic delivery, and difficulties with the administration of multiple doses to a target site. We report the development and application of a therapeutic reservoir device that enables sustained and repeated administration of small molecules, macromolecules and cells directly to organs and tissues of interest via a polymer-based reservoir connected to a subcutaneous port. In a myocardial infarct rodent model, we show that repeated administration of cells over a four-week period using the reservoir provided functional compared to a single injection of cells and to no treatment. Recent advances of the system include a multi-port and multi-reservoir system that can be tailored to cargo and application need. The pre-clinical use of our therapeutic reservoir as a research model may enable insights into regenerative orthopaedic therapy, particularly those therapies that require multi-dose approaches.