Nanoparticle-Reinforced Tough Hydrogel as a Versatile Platform for Pharmaceutical Drug Delivery: Preparation and in Vitro Characterization

Abstract

Natural polymer-based hydrogels are excellent for encapsulating hydrophilic drugs, but they are mechanically weak and degrade easily. In this communication, we exploit the electrostatic interaction between nanosilicates (nSi) and gelatin methacrylate (GelMA) to form a mechanically tough nanocomposite hydrogel for pharmaceutical drug delivery. These hydrogels, prepared at subzero temperatures to form cryogels, displayed macroporous structures, which favors cell infiltration. The designed tough cryogel also showed a slower rate of degradation. Furthermore, we encapsulated the small molecule metformin and sustained the drug release under physiological conditions. Cryogel-loaded metformin reduced the effect of endothelial cell injury caused by nutrient deprivation in vitro. Finally, we hypothesize that this versatile nanocomposite material will find use in diverse biomedical applications.

Engineering multifunctional adhesive hydrogel patches for biomedical applications

“…A robust mechanical strength helps in maintaining the structural integrity of the patch. Adding inorganic fillers, such as nanoparticles, to the hydrogels may increase their mechanical strength 16 . The addition of another polymeric network can also increase the mechanical strength of the hydrogels 33 .…”

“…Additionally, the diameter of the tip has a great impact on skin penetration. It has been found that a tip diameter below 15 μm yields the best results 16,57 . Recently, Han et al.…”

“…Beyond chemical crosslinking strategies, tough hydrogel patches can also be fabricated by integrating multiple polymers in the network, such as interpenetrating network 14 and double network hydrogels 15 . Additionally, mechanically tough hydrogels can be prepared by reinforcing the polymeric network using nanoparticles 16 …”

Tailoring the Inherent Properties of Biobased Nanoparticles for Nanomedicine

“…Biobased nanoparticles can also be delivered with polymeric scaffolds to promote tissue regeneration by providing a suitable platform for cell attachment, cell–cell interaction, and cell modulation. Such polymeric scaffolds comprise of three-dimensional water-swellable hydrogels that can mimic the native extracellular matrices. − Advanced fabrication strategies of hydrogels, such as bioprinting, cryogelation, and electrospinning, can be used for preparing biobased-nanocomposite scaffolds for wound healing, bone regeneration, and cardiac therapy, among others. Additionally, such optimal nanocomposite hydrogel design strategies can be computed using machine learning-based approaches .…”

Amyloid Fibril and Clay Nanosheet Dual-Nanoengineered DNA Dynamic Hydrogel for Vascularized Bone Regeneration

“…Pristine dynamic hydrogels generally exhibit low osteogenic activity, and imparting osteogenic active nanoparticles, such as black phosphorus, bioactive glass, manganese dioxide and nanosilicates, could be effective in promoting osteogenesis. − Clay nanosheets (Na 0.7 Si 8 Mg 5.5 Li 0.3 O 20 (OH) 4 ) are particularly interesting disc-shaped particles with diameters ranging from approximately 25–30 nm and thicknesses of approximately 1 nm. The intrinsic feature of negatively charged on the surface and positively charged at the edge endows clay nanosheets with great binding ability with macromolecules via electrostatic interactions to reinforce hydrogel matrices and also sustainably release bioactive ions, including Si 4+ , Mg 2+ and Li + to further promote osteogenesis. − Furthermore, to ensure augmenting bone regenerative results, the reconstruction of vascular networks is critical. , Unfortunately, the expression levels of endogenous cytokines related to angiogenesis are relatively low during bone defect healing . It has been confirmed that the roles of vascular endothelial growth factor (VEGF) to promote the adhesion and proliferation of HUVECs and angiogenesis regulation, however, it suffers several drawbacks including high cost, immunogenic properties and high doses of VEGF that tend to generate similar capillaries in tumor tissues. − Remarkably, the QK peptide, an alternative VEGF mimetic peptide, can recapitulate the biological activity of full-length VEGF of the benefits with cost-effective synthesis, promising stability, and poor immunogenicity. , The QK peptide has been proven to effectively promote angiogenesis, re-epithelialization and increase granulation tissue formation during wound closure. , To this end, considering the aforementioned characteristics of dynamic hydrogels and bioactivated factors for bone regeneration, we hypothesize that synergistically harnessing amyloid fibrils, clay nanosheets, and QK peptide to fabricate dual-nanoengineered DNA dynamic hydrogel can achieve biologically active control to induce enhanced angiogenesis and osteogenesis, but such therapeutic hydrogels have not been reported.…”