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

工程骨膜可在骨再生过程中有效输送 rhBMP-2 和间充质祖细胞

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作者:Juan Antonio Romero-Torrecilla, José María Lamo-Espinosa, Purificación Ripalda-Cemboráin, Tania López-Martínez, Gloria Abizanda, Luis Riera-Álvarez, Sergio Ruiz de Galarreta-Moriones, Asier López-Barberena, Naiara Rodríguez-Flórez, Reyes Elizalde, Vineetha Jayawarna, José Valdés-Fernández, Miguel Ec

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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