Fig. 1

Composite advanced therapy medicinal product (ATMP) developed for the osteoarticular regeneration (OAR) of cartilage focal lesions. a The ARTiCAR is a composite ATMP that combines an FDA-approved synthetic wound dressing and a living therapeutic made of autologous mesenchymal stem cells (MSCs), embedded in alginate/hyaluronic acid hydrogel. The wound dressing, named NanoM1-BMP2 is made of nanofibrous poly-ε-caprolactone nano-functionalized with Bone morphogenetic protein 2 and aims at subchondral bone regeneration. The cellular hydrogel aims at articular cartilage regeneration. The NanoM1-BMP2 was tested for cytotoxicity in vitro (step 1); the whole ARTiCAR was tested for acute toxicity, biodistribution and persistence in an osteochondral defect nude rat model (step 2) and for feasibility, safety, and non-invasive monitoring of the procedure (step 3) in a sheep intra-articular model. b The ARTiCAR aims at the simultaneous regeneration of both the articular cartilage and the subchondral bone in a one-step surgical procedure. After harvesting MSCs from patient’s bone marrow, the NanoM1-BMP2 is applied in contact with the injured subchondral bone; afterwards, the MSCs mixed with the hydrogel is applied to fill the defect