Dual-crosslinked alginate hydrogels with a high Ca²⁺ content were successfully prepared, which extended their properties, and showed potential application as a skin strain sensor.

MicroRNAs (miRNAs) are being developed to enhance tissue regeneration. Here we show that a hyperbranched polymer with high miRNA-binding affinity and negligible cytotoxicity can self-assemble into nano-sized polyplexes with a ‘double-shell’ miRNA distribution and high transfection efficiency. These polyplexes are encapsulated in biodegradable microspheres to enable controllable two-stage (polyplexes and miRNA) delivery. The microspheres are attached to cell-free nanofibrous polymer scaffolds that spatially control the release of miR-26a. This technology is used to regenerate critical-sized bone defects in osteoporotic mice by targetingGsk-3βto activate the osteoblastic activity of endogenous stem cells, thus addressing a critical challenge in regenerative medicine of achieving cell-free scaffold-based miRNA therapy for tissue engineering.

Hydrogels may exhibit strong adhesion upon embedding nanoparticles into them forming strong/weak bonds (viathe multiple physical or chemical interactions).

Stimuli-responsive polymeric micelles have served as an emerging and interesting platform for poorly soluble drug delivery towards cancer therapy in response to exogenous stimuli (variations in temperature, light, electric field, magnetic field, or ultrasound intensity) and endogenous stimuli (changes in pH, enzyme concentration, or redox gradients). Click chemistry, an attractive synthetic methodology for conjugation, has emerged in nearly all fields of current chemistry including the construction of stimuli-responsive polymeric micelles. Here we summarize a number of pioneering studies in the area of stimuli-responsive polymeric micelles via click chemistry and divide them into six major sections in view of stimulus types (temperature, light, ultrasound, pH, enzymes, and redox). The design, synthesis, and biomedical applications of stimuli-responsive polymeric micelles via click chemistry are highlighted. Recent achievements and further perspectives in this area are briefly discussed as well.