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

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Local delivery of bone morphogenetic protein-2 from near infrared-responsive hydrogels for bone tissue regeneration.
Biomaterials ( IF 12.8 ) Pub Date : 2020-02-21 , DOI: 10.1016/j.biomaterials.2020.119909
Silvia Sanchez-Casanova ₁ , Francisco M Martin-Saavedra ₁ , Clara Escudero-Duch ₂ , Maria I Falguera Uceda ₃ , Martin Prieto ₄ , Manuel Arruebo ₄ , Paloma Acebo ₅ , Mario L Fabiilli ₆ , Renny T Franceschi ₇ , Nuria Vilaboa ₁

Affiliation

Hospital Universitario La Paz-IdiPAZ, Paseo de La Castellana 261, Madrid, 28046, Spain; CIBER de Bioingenieria, Biomateriales y Nanomedicina, CIBER-BBN, Spain.
CIBER de Bioingenieria, Biomateriales y Nanomedicina, CIBER-BBN, Spain; Hospital Universitario La Paz-IdiPAZ, Paseo de La Castellana 261, Madrid, 28046, Spain.
Hospital Universitario La Paz-IdiPAZ, Paseo de La Castellana 261, Madrid, 28046, Spain.
Departmento de Ingenieria Quimica, Instituto de Nanociencia de Aragon (INA), Universidad de Zaragoza, Campus Rio Ebro. Edificio I+D, C/ Mariano Esquillor s/n, Zaragoza, 50018, Spain; Instituto de Ciencia de Materiales de Aragon, Consejo Superior de Investigaciones Cientificas (ICMA-CSIC), Universidad de Zaragoza, Zaragoza, 50009, Spain; CIBER de Bioingenieria, Biomateriales y Nanomedicina, CIBER-BBN, Spain.
Unidades Centrales Cientifico Tecnicas-Servicio de Veterinaria. Instituto de Salud Carlos III, Crta. Majadahonda a Pozuelo Km.2, Majadahonda, Madrid, 28220, Spain; Unidad de Terapias Farmacologicas-Instituto de Investigacion de Enfermedades Raras. Instituto de Salud Carlos III, Crta. Majadahonda a Pozuelo Km.2, Majadahonda, Madrid, 28220, Spain.
Applied Physics Program, University of Michigan, Ann Arbor, MI, USA; Department of Radiology, University of Michigan Health System, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA; Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI, USA.

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.

中文翻译：

从近红外响应水凝胶中局部递送骨形态发生蛋白 2 用于骨组织再生。

实现生长因子产生的时空控制仍然是组织工程的主要目标。在目前的工作中，我们将诱导型转基因表达和近红外 (NIR) 响应水凝胶技术相结合，开发了一个骨再生治疗平台。将热激活和依赖二聚体的转基因表达系统整合到间充质干细胞中，以有条件地控制骨形态发生蛋白 2 (BMP-2) 的产生。基因工程细胞被困在基于纤维蛋白和等离子体金纳米粒子的水凝胶中，这些纳米粒子将 NIR 激光的入射能量转化为热量。在二聚体存在的情况下，光诱导的温和热疗会诱导生物活性 BMP-2 从 NIR 响应细胞构建体中释放。在免疫能力强的小鼠颅盖骨中产生的临界大小的骨缺损，充满了近红外响应水凝胶，捕获在热激活和二聚体依赖性基因回路的控制下表达 BMP-2 的细胞。在用二聚体处理的动物中，植入物的 NIR 照射诱导骨病变中 BMP-2 的产生。在骨缺损中诱导有条件地表达 BMP-2 的 NIR 响应细胞构建体导致新矿化组织的形成，从而表明该技术平台的治疗潜力。

更新日期：2020-02-21

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