期刊
BIOMATERIALS
卷 241, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.119909
关键词
Near-infrared; Gene therapy; Bone morphogenetic protein 2; Hydrogel; Gold nanoparticles; Bone regeneration
资金
- ISCIII-Fondos FEDER, Ministerio de Economia y Competitividad (MINECO), Spain [PI15/01118]
- Ministerio de Ciencia, Innovacion y Universidades (MICINN), Spain [RTI2018-095159B-I00]
- grant Roche-IdiPAZ from the intramural funding program of Foundation for Biomedical Research of Hospital Universitario La Paz-IdiPAZ
- ERC Consolidator Grant program [ERC-2013-CoG-614715]
- NIH, United States [R21AR072336]
- HSF Pharmaceuticals S.A.
- ISCIII-Fondos FEDER, Ministerio de Economia y Competitividad (MINECO) [FI14/00447]
- Program I2 from Comunidad Autonoma de Madrid
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.
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