An engineered periosteum for efficient delivery of rhBMP-2 and mesenchymal progenitor cells during bone regeneration
Juan Antonio Romero‐Torrecilla, José María Lamo-Espinosa, Purificación Ripalda‐Cemboráin, Tania López‐Martínez, Gloria Abizanda, Luís Riera-Álvarez, Sergio Ruiz de Galarreta, Asier López-Barberena, Naiara Rodríguez-Flórez, Reyes Elizalde, Vineetha Jayawarna, José Valdés‐Fernández, Miguel Echanove-González de Anleo, Peter Childs, Elena M. De‐Juan‐Pardo, Manuel Salmerón‐Sánchez, Felipe Prósper, Emma Muiños Lopeź, Froilán Granero‐Moltó
Abstract
During bone regeneration, the periosteum acts as a carrier for key regenerative cues, delivering osteochondroprogenitor cells and crucial growth factors to the injured bone. We developed a biocompatible, 3D polycaprolactone (PCL) melt electro-written membrane to act as a mimetic periosteum. Poly (ethyl acrylate) coating of the PCL membrane allowed functionalization, mediated by fibronectin and low dose recombinant human BMP-2 (rhBMP-2) (10-25 μg/ml), resulting in efficient, sustained osteoinduction in vitro. In vivo, rhBMP-2 functionalized mimetic periosteum demonstrated regenerative potential in the treatment of rat critical-size femoral defects with highly efficient healing and functional recovery (80%-93%). Mimetic periosteum has also proven to be efficient for cell delivery, as observed through the migration of transplanted periosteum-derived mesenchymal cells to the bone defect and their survival. Ultimately, mimetic periosteum demonstrated its ability to deliver key stem cells and morphogens to an injured site, exposing a therapeutic and translational potential in vivo when combined with unprecedentedly low rhBMP-2 doses.