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Despite many advances and optimization in colon cancer treatment, tumor recurrence and metastases make the development of new therapies necessary.Colon cancer stem cells (CCSCs) are considered as the main triggering factor of cancer progression, recurrence, and metastasis. CCSCs as a result of accumulated genetic and epigenetic alterations and also complex interconnection with the tumor microenvironment (TME) can evolve and convert to full malignant cells. Mounting evidence suggests that in cancer therapy both CCSCs and non-CCSCs in TME have to be regarded to break through the limitation of current therapies. In this regard, stem cell capabilities of some non-CCSCs may arise inside the TME condition. Therefore, a deep knowledge of regulatory mechanisms, heterogeneity, specific markers, and signaling pathways of CCSCs and their interconnection with TME components is needed to improve the treatment of colorectal cancer and the patient's life quality. In this review, we address current different targeted therapeutic options that target cell surface markers and signaling pathways of CCSCs and other components of TME.Current challenges and future perspectives of colon cancer personalized therapy are also provided here. Taken together, based on the deep understanding of biology of CCSCs and using three-dimensional culture technologies, it can be possible to reach successful colon cancer eradication and improvise combination targeted therapies against CCSCs and TME. K E Y W O R D Scolon cancer stem cells, colorectal cancer, combination therapy, complex interaction, signaling pathways, tumor microenvironment

Silica nanomaterials (SNMs) and their composites have recently been investigated as scaffolds for bone tissue engineering. SNM scaffolds possess the ability to encourage bone cell growth and also allow the simultaneous delivery of biologically active biomolecules that are encapsulated in the mesopores. Their high mechanical strength, low cytotoxicity, ability to stimulate both the proliferation and osteogenic differentiation of progenitor cells make the SNMs appropriate scaffolds. Their physiochemical properties facilitate the cell spreading process, allow easy access to nutrients and help the cell-cell communication process during bone tissue engineering. The ability to deliver small biomolecules, such as dexamethasone, different growth factors, vitamins and mineral ions depends on the morphology, porosity, and crystallinity of SNMs and their composites with other polymeric materials. In this review, the abilities of SNMs to perform as suitable scaffolds for bone tissue engineering are comprehensively discussed.

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