Injectable Multicomponent Biomimetic Gel Composed of Inter-Crosslinked Dendrimeric and Mesoporous Silica Nanoparticles Exhibits Highly Tunable Elasticity and Dual Drug Release Capacity.

There is a growing need for cartilage defect grafts that are structurally adaptable to possess multifaceted functions to promote bone regeneration, sustain medication efficacy, and preferably remain injectable but solidify quickly upon injection. In this work, we developed an injectable multicomponent biomimetic gel (MBG) by integrating polyamidoamine dendrimer G3 (G3), mesoporous silica nanoparticles (MSNs), and dendrimer-templated silver nanoparticles (G3-Ag) into a well-defined cross-linked network. MBGs composed of one particulate component (G3 alone), i.e., MBG-1, two particulate components (G3 and MSN-NH2), i.e., MBG-2, and three particulate components (G3, MSN-NH2, and G3-Ag), i.e., MBG-3, were prepared by inter-cross-linking dendrimeric and mesoporous silica nanoparticles with poly(ethylene glycol) diglycidyl ether (PEG-DGE, Mn = 2000 g/mol) via the facile amine-epoxy click reaction. The water-soluble antibiotic isoniazid was loaded to the cross-linked PEG network, whereas the hydrophobic antibiotic rifampicin was encapsulated into mesoporous MSNs. Our studies revealed that elasticity and mechanical strengths could be modulated and enhanced significantly with the inclusion of MSNs and silver nanoparticles. Isoniazid was released rapidly while rifampicin was released over an extended period of time. In addition, MBGs showed injectability, high swelling capacity, structural stability, and cytocompatibility. Taken together, MBGs have shown structural features that allow for the development of injectable gel grafts with the ability to promote cartilage defect repair and offer antibiotic medication benefits.