An integrated long-acting implant of clinical safe cells, drug and biomaterials effectively promotes spinal cord repair and restores motor functions.

Spinal cord injury (SCI) is incurable and raises growing concerns. The main barrier to nerve repair is the complicated inhibitory microenvironment, where single-targeted strategies are largely frustrated. Despite the progress in combinatory therapeutic systems, the development and translation of effective therapies remain a challenge with extremely limited clinical materials. In this study, mesenchymal stem cells are transplanted in combination with sustained release of methylprednisolone through delivery in one composite matrix of a microsphere-enveloped adhesive hydrogel. All the materials used, including the stem cells, drug, and the matrix polymers gelatin and hyaluronan, are clinically approved. The therapeutic effects and safety issues are evaluated on rat and canine SCI models. The implantation significantly promotes functional restoration and nerve repair in a severe long-span rat spinal cord transection model. Distant spinal cord segments and the urinary system are effectively protected against pathologic damage. Moreover, the local sustained drug delivery mitigates the inflammatory microenvironment when overcoming the clinical issue of systemic side effects. The study presents an innovative strategy to achieve safe and efficient combinatory treatment of SCI.