title: A tissue-engineered therapeutic device inhibits tumor growth in vitro and in vivo.
abstract: Bone metastasis is one of the leading causes of death in breast cancer patients. The current treatment is performed as a palliative therapy and the adverse side effects can compromise the patients' quality of life. In order to both effectively treat bone metastasis and avoid the limitation of current strategies, we have invented a drug eluting scaffold with clay matrix release doxorubicin (DESCLAYMR_DOX) to mechanically support the structure after resecting the metastatic tissue while also releasing the anticancer drug doxorubicin which supplements growth inhibition and elimination of the remaining tumor cells. We have previously demonstrated that this device has the capacity to regenerate the bone and provide sustained release of the anticancer drug in vitro. In this study, we focus on the ability of the device to inhibit cancer cell growth in vitro as well as in vivo. Drug-release kinetics was investigated and the cell viability test showed that the tumor inhibitory effect is sustained for up to 4weeks in vitro. Subcutaneous implantation of DESCLAYMR_DOX in athymic mice resulted in significant growth inhibition of human tumor xenografts of breast origin and decelerated multi-organ metastasis formation. Fluorescence images, visualizing doxorubicin, showed a sustained drug release from the DESCLAYMR device in vivo. Furthermore, local use of DESCLAYMR_DOX implantation reduced the incidence of doxorubicin's cardio-toxicity. These results suggest that DESCLAYMR_DOX can be used in reconstructive surgery to support the structure after bone tumor resection and facilitate a sustained release of anticancer drugs in order to prevent tumor recurrence.
authors: Orthopaedic Research Lab, Aarhus University Hospital, Aarhus C, Denmark. Electronic address: mingsun.health@gmail.com.
authors: Ming
authors: M
authors: Sun
authors: Orthopaedic Research Lab, Aarhus University Hospital, Aarhus C, Denmark.
authors: Miao
authors: M
authors: Wang
authors: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, Denmark. Electronic address: chen.muwan@inano.au.dk.
authors: Muwan
authors: M
authors: Chen
authors: Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
authors: Frederik
authors: F
authors: Dagnaes-Hansen
authors: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, Denmark.
authors: Dang Quang Svend
authors: DQ
authors: Le
authors: Orthopaedic Research Lab, Aarhus University Hospital, Aarhus C, Denmark.
authors: Anette
authors: A
authors: Baatrup
authors: Experimental Clinical Oncology Department, Aarhus University Hospital, Aarhus C, Denmark.
authors: Michael R
authors: MR
authors: Horsman
authors: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, Denmark.
authors: Jørgen
authors: J
authors: Kjems
authors: Orthopaedic Research Lab, Aarhus University Hospital, Aarhus C, Denmark.
authors: Cody Eric
authors: CE
authors: Bünger
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D005355:Fibrosis; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology*; D012996:Solutions; D023822:Tissue Engineering / Q000295:instrumentation*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D012996:Solutions; D004317:Doxorubicin
keywords: Bone metastases; Bone substitute; Local drug delivery; Tissue engineered therapeutic device; Tumor inhibition