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

Author:

Romero-Torrecilla Juan Antonio,Lamo-Espinosa José María,Ripalda-Cemboráin PurificaciónORCID,López-Martínez TaniaORCID,Abizanda Gloria,Riera-Álvarez Luis,de Galarreta-Moriones Sergio RuizORCID,López-Barberena Asier,Rodríguez-Flórez NaiaraORCID,Elizalde Reyes,Jayawarna Vineetha,Valdés-Fernández José,de Anleo Miguel Echanove-González,Childs PeterORCID,de Juan-Pardo Elena,Salmeron-Sanchez Manuel,Prósper FelipeORCID,Muiños-López EmmaORCID,Granero-Moltó FroilánORCID

Abstract

AbstractDuring 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.

Funder

EC | Horizon 2020 Framework Programme

PhD student fellowship of Asociación de Amigos de la Universidad de Navarra.

PhD Student fellowship from Asociación de Amigos de la Universidad de Navarra

PhD Student fellowship from Fundación para la Investigación Médica Aplicada

RCUK | Engineering and Physical Sciences Research Council

Departamento de Educación, Gobierno de Navarra

Publisher

Springer Science and Business Media LLC

Subject

Cell Biology,Developmental Biology,Biomedical Engineering,Medicine (miscellaneous)

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