TY - JOUR
T1 - An engineered periosteum for efficient delivery of rhBMP-2 and mesenchymal progenitor cells during bone regeneration
AU - Romero-Torrecilla, Juan Antonio
AU - Lamo-Espinosa, José María
AU - Ripalda-Cemboráin, Purificación
AU - López-Martínez, Tania
AU - Abizanda, Gloria
AU - Riera-Álvarez, Luis
AU - de Galarreta-Moriones, Sergio Ruiz
AU - López-Barberena, Asier
AU - Rodríguez-Flórez, Naiara
AU - Elizalde, Reyes
AU - Jayawarna, Vineetha
AU - Valdés-Fernández, José
AU - de Anleo, Miguel Echanove González
AU - Childs, Peter
AU - de Juan-Pardo, Elena
AU - Salmeron-Sanchez, Manuel
AU - Prósper, Felipe
AU - Muiños-López, Emma
AU - Granero-Moltó, Froilán
N1 - Funding 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”.
Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85173584379&partnerID=8YFLogxK
U2 - 10.1038/s41536-023-00330-2
DO - 10.1038/s41536-023-00330-2
M3 - Article
C2 - 37773177
AN - SCOPUS:85173584379
SN - 2057-3995
VL - 8
JO - npj Regenerative Medicine
JF - npj Regenerative Medicine
IS - 1
M1 - 54
ER -