Abstract
The development of multifunctional biomaterials to repair bone defects after neoplasm removal and inhibit tumor recurrence remained huge clinical challenges. Here, we demonstrate a kind of innovative and multifunctional magnetic mesoporous calcium sillicate/chitosan (MCSC) porous scaffolds, made of M-type ferrite particles (SrFe12O19), mesoporous calcium silicate (CaSiO3) and chitosan (CS), which exert robust anti-tumor and bone regeneration properties. The mesopores in the CaSiO3 microspheres contributed to the drug delivery property, and the SrFe12O19 particles improved photothermal therapy (PTT) conversion efficacy. With the irradiation of NIR laser, doxorubicin (DOX) was rapidly released from the MCSC/DOX scaffolds. In vitro and in vivo tests demonstrated that the MCSC scaffolds possessed the excellent anti-tumor efficacy via the synergetic effect of DOX drug release and hyperthermia ablation. Moreover, BMP-2/Smad/Runx2 pathway was involved in the MCSC scaffolds promoted proliferation and osteogenic differentiation of human bone marrow stromal cells (hBMSCs). Taken together, the MCSC scaffolds have the ability to promote osteogenesis and enhance synergetic photothermal-chemotherapy against osteosarcoma, indicating MCSC scaffolds may have great application potential for bone tumor-related defects.
Highlights
Bone metastasis has been commonly observed in malignant tumors, notably for patients with breast cancer, lung cancer or kidney cancer[1,2]
Research carried out on humans must be in compliance with the Helsinki Declaration, human bone marrow-derived mesenchymal stem cells and bone tissue were obtained from four donors who gave their written informed consent
No limiting adsorption at high P/Po in the type H3 loop demonstrated that the mesopores within the microspheres exhibited the slit-shaped pores with pore size of approximately 2.17 nm (Fig. 2D), which was consistent with the result of transmission electron microscopy (TEM) analysis
Summary
Bone metastasis has been commonly observed in malignant tumors, notably for patients with breast cancer, lung cancer or kidney cancer[1,2]. Previous studies suggested that residual tumor cells could be effectively killed by controlled drug delivery system mediated photothermal therapy (PTT)[5,6]. Mesoporous CaSiO3 has been widely used for both controlled drug delivery systems and bone repair applications due to good biocompatibility, drug loading efficiency and sustained drug release performance[8]. The chemotherapeutic drugs loaded-mesoporous CaSiO3 scaffolds may combine bone regenerative abilities with anti-tumor properties. Conventional photothermal agents mainly include gold nanomaterials[12,13], copper nanomaterials[14], carbonnano materials[15], near infrared (NIR) dyes[16,17] and magnetic ironoxide nanoparticles[18,19], in which these regimens show good NIR absorption property. The scaffold incorporated with M-type ferrite particles may overcome these drawbacks, and may be considered a promising biomatrix for bone engineering
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