Cartilage degeneration is among the fundamental reasons behind disability and pain across the globe. Numerous approaches have been employed to treat cartilage diseases. Nevertheless, none have shown acceptable outcomes in the long run. In this regard, the convergence of tissue engineering and microfabrication principles can allow developing more advanced microfluidic technologies, thus offering attractive alternatives to current treatments and traditional constructs used in tissue engineering applications. Herein, the current developments involving microfluidic hydrogel‐based scaffolds, promising structures for cartilage regeneration, ranging from hydrogels with microfluidic channels to hydrogels prepared by the microfluidic devices, that enable therapeutic delivery of cells, drugs, and growth factors, as well as cartilage‐related organ‐on‐chips are reviewed. Thereafter, cartilage anatomy and types of damages, and present treatment options are briefly overviewed. Various hydrogels are introduced, and the advantages of microfluidic hydrogel‐based scaffolds over traditional hydrogels are thoroughly discussed. Furthermore, available technologies for fabricating microfluidic hydrogel‐based scaffolds and microfluidic chips are presented. The preclinical and clinical applications of microfluidic hydrogel‐based scaffolds in cartilage regeneration and the development of cartilage‐related microfluidic chips over time are further explained. The current developments, recent key challenges, and attractive prospects that should be considered so as to develop microfluidic systems in cartilage repair are highlighted.

A new two-step method is suggested for the preparation of homogeneous alginate gels. In the first step, alginate chains are weakly bonded by Ca2+ ions in an aqueous solution with a low pH. In the next step, the gel is immersed into a strong solution of CaCl2 to finalize the cross-linking process. Homogeneous alginate gels preserve their integrity in aqueous solutions with a pH ranging from 2 to 7 and ionic strength in the interval from 0 to 0.2 M, at temperatures ranging from room temperature up to 50 °C, and can be used in biomedical applications. The immersion of these gels into aqueous solutions with low pH induces the partial breakage of ionic bonds between chains (treated as gel degradation). This degradation affects the equilibrium and transient swelling of homogeneous alginate gels and makes them sensitive to the history of loading and environmental conditions (pH, ionic strength and temperature of aqueous solutions). As sensitivity to the environmental stimuli is a characteristic feature of polymer networks connected by catch bonds, homogeneous alginate gels may serve as a simple model, mimicking the behavior of more sophisticated structures in living matter.

Ionically, cross-linked alginate gels have a potential to be used in a wide range of biomedical, environmental and catalytic applications. The study deals with preparation of alginate hydrogels cross-linked with various cations and the analysis of their equilibrium swelling and mechanical properties. It is shown that the type of cations used in the cross-linking process affects the elastic moduli and the equilibrium degree of swelling of the gels. The experimental data in small-amplitude oscillatory tests are fitted with a model that involves two material parameters: the elastic modulus of a polymer network and a measure of its inhomogeneity. The influence of cations on these quantities is studied numerically. It is revealed that the dependence of the elastic modulus of ionically cross-linked alginate gels on their equilibrium degree of swelling differs from that predicted by the conventional theory for covalently cross-linked gels.

Nowadays, heart disease, especially myocardial infarction, is one of the most astoundingly unfortunate causes of mortality in the world. That is why special attention has been paid toward tissue engineering techniques for curing and regeneration of heart tissue. In this study, poly(N-isopropyl acrylamide) (PNIPAAm), a temperature-sensitive injectable hydrogel, was selected as a minimally invasive scaffold to accommodate, carry, and release of niosomal rosuvastatin to the inflicted area for inducing angiogenesis and thus accelerating the healing process. The characteristics of PNIPAAm were studied by scanning electron microscopy, rheology tests, and Fourier transform infrared spectroscopy. The properties of the niosomal rosuvastatin release system, including particle size distribution, zeta potential, encapsulation efficiency (EE), and drug release, were also studied. The results showed that niosomes (358 nm) had a drug EE of 78% and a loading capacity of 53%. The drug was sustainably released from the system up to about 54% in 5 d. Cellular studies showed no toxicity to the endothelial cell lines, and the niosomal drug with a concentration of 7.5 nM enhanced cell proliferation, and cell migration increased from 72% to 90% compared to the control sample. Therefore, the controlled-release of niosomal rosuvastatin enhanced angiogenesis in a dose-dependent manner. Taken together, these advantages suggest that PNIPAAm-based niosomal hydrogel provides a promising candidate as an angiogentic injectable scaffold for potential cardiac tissue regeneration.

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