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

Romero-Torrecilla, J. A. et al. (2023) An engineered periosteum for efficient delivery of rhBMP-2 and mesenchymal progenitor cells during bone regeneration. npj Regenerative Medicine, 8, 54. (doi: 10.1038/s41536-023-00330-2) (PMID:37773177) (PMCID:PMC10541910)

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.

• Item Type: Articles
• Additional Information: This work was supported by funds of the Ministerio de Ciencia e Investigación through Instituto de Salud Carlos III and European Regional Development Funds (A way to make Europe) (PI17/00136, PI20/00076) to F.G.M. and ISC-RETICS (RD16/0011/005) and Next Generation EU, Plan de Recuperación, Transformación y Resiliencia RICORS TERAV ISCIII (RD21/0017/0009) and European Union Horizon 2020 MSCA-RISE (grant agreement #872648, MEPHOS) to F.P., European Union Horizon 2020 program (grant agreement #874889, HEALIKICK) to M.S.S. and F.G.M., EPSRC Programme grant (EP/P001114/1) to M.S.-S. and Departamento de Desarrollo Económico del Gobierno de Navarra (PC009-010-011 and PC073-074-075, 3DMedical) to F.G.M. J.A. Romero-Torrecilla was supported by a fellowship of “Asociación de Amigos de la Universidad de Navarra” and “Obra Social La Caixa”; the research leading to these results received funding from “la Caixa” Banking Foundation. J.V.F. was supported by a fellowship from “Asociación de Amigos de la Universidad de Navarra”, and M.E.G.A. is supported by a CIMA AC fellowship from “Fundación para la Investigación Médica Aplicada”.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Salmeron-Sanchez, Professor Manuel and Jayawarna, Dr Vineetha and Childs, Dr Peter
• Authors: Romero-Torrecilla, J. A., Lamo-Espinosa, J. M., Ripalda-Cemboráin, P., López-Martínez, T., Abizanda, G., Riera-Álvarez, L., de Galarreta-Moriones, S. R., López-Barberena, A., Rodríguez-Flórez, N., Elizalde, R., Jayawarna, V., Valdés-Fernández, J., Echanove-González de Anleo, M., Childs, P., de Juan-Pardo, E., Salmeron-Sanchez, M., Prósper, F., Muiños-López, E., and Granero-Moltó, F.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences; College of Science and Engineering > School of Engineering > Biomedical Engineering
• Journal Name: npj Regenerative Medicine
• Publisher: Nature Research
• ISSN: 2057-3995
• ISSN (Online): 2057-3995
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in npj Regenerative Medicine 8: 54
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
173192		Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicine	Manuel Salmeron-Sanchez	Engineering and Physical Sciences Research Council (EPSRC)	EP/P001114/1	ENG - Biomedical Engineering