Local delivery of bone morphogenetic protein-2 from near infrared-responsive hydrogels for bone tissue regeneration

Sanchez-Casanova, Silvia ; Martin-Saavedra, Francisco M. ; Escudero-Duch, Clara ; Falguera Uceda, María I. ; Prieto, Martín ; Arruebo, Manuel (Universidad de Zaragoza) ; Acebo, Paloma ; Fabiilli, Mario L. ; Franceschi, Renny T. ; Vilaboa, Nuria

Resumen: Achievement of spatiotemporal control of growth factors production remains a main goal in tissue engineering. In the present work, we combined inducible transgene expression and near infrared (NIR)-responsive hydrogels technologies to develop a therapeutic platform for bone regeneration. A heat-activated and dimerizer-dependent transgene expression system was incorporated into mesenchymal stem cells to conditionally control the production of bone morphogenetic protein 2 (BMP-2). Genetically engineered cells were entrapped in hydrogels based on fibrin and plasmonic gold nanoparticles that transduced incident energy of an NIR laser into heat. In the presence of dimerizer, photoinduced mild hyperthermia induced the release of bioactive BMP-2 from NIR-responsive cell constructs. A critical size bone defect, created in calvaria of immunocompetent mice, was filled with NIR-responsive hydrogels entrapping cells that expressed BMP-2 under the control of the heat-activated and dimerizer-dependent gene circuit. In animals that were treated with dimerizer, NIR irradiation of implants induced BMP-2 production in the bone lesion. Induction of NIR-responsive cell constructs conditionally expressing BMP-2 in bone defects resulted in the formation of new mineralized tissue, thus indicating the therapeutic potential of the technological platform.

Idioma: Inglés

DOI: 10.1016/j.biomaterials.2020.119909

Año: 2020

Publicado en: Biomaterials 241 (2020), 119909 1-15
ISSN: 0142-9612

Factor impacto JCR: 12.479 (2020)

Categ. JCR: MATERIALS SCIENCE, BIOMATERIALS rank: 2 / 40 = 0.05 (2020) - Q1 - T1
Categ. JCR: ENGINEERING, BIOMEDICAL rank: 3 / 90 = 0.033 (2020) - Q1 - T1

Factor impacto SCIMAGO: 3.209 - Bioengineering (Q1) - Biomaterials (Q1) - Nanoscience and Nanotechnology (Q1) - Ceramics and Composites (Q1) - Mechanics of Materials (Q1) - Biophysics (Q1)

Financiación: info:eu-repo/grantAgreement/EC/FP7/614715/EU/A Photo-triggered On-demand Drug Delivery System for Chronic Pain/NANOHEDONISM
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI15-01118
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RTI2018-095159-B-100

Tipo y forma: Artículo (PostPrint)

Área (Departamento): Área Ingeniería Química (Dpto. Ing.Quím.Tecnol.Med.Amb.)