An engineered periosteum for efficient delivery of rhBMP-2 and mesenchymal progenitor cells during bone regeneration

Romero-Torrecilla, Juan Antonio and Lamo-Espinosa, José María and Ripalda-Cemboráin, Purificación and López-Martínez, Tania and Abizanda, Gloria and Riera-Álvarez, Luis and de Galarreta-Moriones, Sergio Ruiz and López-Barberena, Asier and Rodríguez-Flórez, Naiara and Elizalde, Reyes and Jayawarna, Vineetha and Valdés-Fernández, José and de Anleo, Miguel Echanove-González and Childs, Peter and de Juan-Pardo, Elena and Salmeron-Sanchez, Manuel and Prósper, Felipe and Muiños-López, Emma and Granero-Moltó, Froilán (2023) An engineered periosteum for efficient delivery of rhBMP-2 and mesenchymal progenitor cells during bone regeneration. NPJ Regenerative Medicine, 8 (1). 54. ISSN 2057-3995 (https://doi.org/10.1038/s41536-023-00330-2)

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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.

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