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

Abstract

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 dendrimertemplated 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-NH 2 ), i.e., MBG-2, and three particulate components (G3, MSN-NH 2 , and G3-Ag), i.e., MBG-3, were prepared by intercross-linking dendrimeric and mesoporous silica nanoparticles with poly(ethylene glycol) diglycidyl ether (PEG-DGE, M n = 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.

Dendrimer-based drug delivery systems: history, challenges, and latest developments

“…The multifunctionality and well-defined nanostructure make dendrimer an ideal building block for producing three-dimensional cross-linked networks, named dendrimer hydrogel (DH) [ 95 – 97 ]. Many chemical and physical ways were developed to cross-link dendrimers to form hydrogels [ 97 – 103 ]. Recently, we developed a DH platform using the aza-Michael addition cross-linking strategy and explored its application as local drug delivery system (Fig.…”

Nanocomposite hydrogels for biomedical applications

“…MSNs and G3‐Ag can improve the mechanical properties of hydrogels. Additionally, rifampicin encapsulated in MSNs can achieve long‐term release 139 . Compared to antibiotic therapy, photodynamic therapy (PDT) based on nanomaterials is also a hot topic that has recently been explored.…”

“…Additionally, rifampicin encapsulated in MSNs can achieve long‐term release. 139 Compared to antibiotic therapy, photodynamic therapy (PDT) based on nanomaterials is also a hot topic that has recently been explored. In the process of cartilage formation and differentiation, ROS produced by PDT are necessary for cell survival, proteoglycan secretion, and cartilage formation.…”

Advanced injectable hydrogels for cartilage tissue engineering

“…Moreover, the N/MPs adsorbs and retain essential stimulating factors, prolonging their release time due to the larger surface-to-volume ratio and high encapsulation efficiency of stimulating factor ( Amiri et al, 2017 ; Nagahama et al, 2018 ; Wong et al, 2018 ; Ishihara et al, 2019 ; Bian et al, 2021 ; Zewail et al, 2021 ; Luu et al, 2022 ; Seo et al, 2022 ). Wang et al (2020b) loaded the water-soluble antibiotic isoniazid into a cross-linked PEG network and encapsulated the hydrophobic antibiotic rifampicin into mesoporous silica nanoparticles. The addition of nanoparticles can significantly adjust and enhance injectable hydrogels' mechanical strength and elasticity.…”