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Development of a vascularized liver tissue construct is a need of an hour to circumvent the current demand of liver transplantation in health care sector. An appropriate matrix must support liver cell viability, functionality, and development of microvasculature. With this perspective, here, we report the use of decellularized caprine liver extracellular matrix (CLECM) derived hydrogel for tissue engineering applications. First, CLECM was used as a substrate coating material for 2D hepatocyte culture. HepG2 cells cultured on CLECM-coated surface showed higher albumin, urea, glycogen, and GAGs synthesis in comparison with collagen-coated surface (taken as control for the study). Thereafter, the cells were encapsulated in CLECM hydrogels for 3D culture. In CLECM hydrogels, HepG2 cells showed highly differentiated and polarized phenotype with the appearance of bile canaliculi-like structures and enhanced expression of mature hepatocyte markers. We further showed that CLECM hydrogels also supported the development of microvasculature in vitro, thus making it a suitable candidate for development of a prevascularized liver tissue construct. In conclusion, we proved the superiority of CLECM over collagen for 2D/3D human hepatocyte and endothelial cell culture. CLECM could serve as an efficient biomaterial platform in the development of a liver tissue construct for application in tissue engineering.

The development of theranostic mesoporous hollow silica nanospheres having therapeutic and diagnostic functions has been achieved. The exterior surface of the hollow mesoporous silica nanosphere was selectively acid functionalized and utilised to conjugate the anticancer drug cisplatin, the marker molecule folic acid (FA), and rhodamine isothiocyanate (RITC), whereas the interior space was utilised to encapsulate superparamagnetic CoFe2O4 nanoparticles as well as the hydrophobic anticancer drug pemetrexed. The hydrodynamic size of the synthesized multidrug loaded hollow particles is 130 nm in physiological pH and it is consistent over a long period. To the best of our knowledge this is the first report on fluorescent magnetic hollow spheres loaded with multiple therapeutic cargoes as well as a magnetic resonance imaging (MRI) contrast agent. The as prepared hollow spheres are biocompatible. The internalization efficiency of the drug loaded particle has been evaluated on folate receptor overexpressed (FR+ve) HeLa, FR-ve HaCat and 3T3 cells. These drug loaded nanospheres exhibit enhanced cytotoxicity as compared to individual drugs. Such a strategy in the simultaneous administration of pemetrexed and platin drugs may open up opportunities for the treatment of lung cancer at its early stage.

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