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Repairing significant bone defects remains a critical challenge, raising the clinical demand to design novel bone biomaterials that incorporate osteogenic and angiogenic properties to support the regeneration of vascularized bone. Bioactive glass scaffolds can stimulate angiogenesis and osteogenesis. In addition, natural or synthetic polymers exhibit structural similarity with extracellular matrix (ECM) components and have superior biocompatibility and biodegradability. Thus, there is a need to prepare composite scaffolds of hydrogels for vascularized bone, which incorporate to improve the mechanical properties and bioactivity of natural polymers. In addition, those composites' 3-dimensional (3D) form offer regenerative benefits such as direct doping of the scaffold with ions. This review presents a comprehensive discussion of composite scaffolds incorporated with BaG, focusing on their effects on osteo-inductivity and angiogenic properties. Moreover, the adaptation of the ion-doped hydrogel composite scaffold into a 3D scaffold for the generation of vascularized bone tissue is exposed. Finally, we highlight the challenges and future of manufacturing such biomaterials.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants have been used by indigenous people across the world for centuries to help individuals preserve their wellbeing and cure diseases. Annona muricata L. (Graviola) which is belonging to the Annonaceae family has been traditionally used due to its medicinal abilities including antimicrobial, anti-inflammatory, antioxidant and cancer cell growth inhibition. Graviola is claimed to be a potential antitumor due to its selective cytotoxicity against several cancer cell lines. However, the metabolic mechanism information underlying the anticancer activity remains limited. AIM OF THE STUDY: This study aimed to investigate the effect of ionic liquid-Graviola fruit pulp extract (IL-GPE) on the metabolomics behavior of colon cancer (HT29) by using an untargeted GC-TOFMS-based metabolic profiling. MATERIALS AND METHODS: Multivariate data analysis was used to determine the metabolic profiling, and the ingenuity pathway analysis (IPA) was used to predict the altered canonical pathways after treating the HT29 cells with crude IL-GPE and Taxol (positive control). RESULTS: The principal components analysis (PCA) identified 44 metabolites with the most reliable factor loading, and the cluster analysis (CA) separated three groups of metabolites: metabolites specific to the non-treated HT29 cells, metabolites specific to the treated HT29 cells with the crude IL-GPE and metabolites specific to Taxol treatment. Pathway analysis of metabolomic profiles revealed an alteration of many metabolic pathways, including amino acid metabolism, aerobic glycolysis, urea cycle and ketone bodies metabolism that contribute to energy metabolism and cancer cell proliferation. CONCLUSION: The crude IL-GPE can be one of the promising anticancer agents due to its selective inhibition of energy metabolism and cancer cell proliferation.
