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pH-responsive nanoparticles (NPs) comprised of degradable carboxymethyl chitosan (CMCS) crosslinked with CaCl 2 were simply prepared via ionic gelation. Fabrication conditions including insulin dosage, CMCS concentration, and crosslinking density were systematically investigated for insulin loading and release in vitro . The encapsulation efficiencies (EE), loading capacity (LC) and average size of the NPs decreased with the increasing insulin concentrations (<0.192 mg/mL), while they notably increased as the insulin dosage was above 0.192 mg/mL. When the concentration of CMCS increased from 0.5 to 2.0 mg/mL, the EE of the NPs reduced while the size of the NPs increased. We further demonstrated that crosslinking density offered a simple method for tuning the properties of the NPs towards various insulin concentrations. The mass ratio 10:5 of CMCS to CaCl 2 exhibited the optimal performance at higher insulin concentration, whereas a higher crosslinking density of 10:7 (m:m) gave the optimal performance at low insulin concentration. The cumulative release of insulin from insulin loaded NPs decreased with the elevating crosslinking density. These findings not only provided a better understanding of the synthesis of CMCS NPs but also contributed to the practical applications of insulin loading and release. [ABSTRACT FROM AUTHOR]

In situ 3D printing technologies is a new frontier for highly personalized medicine, which requires suitable bioink with rheology, biocompatibility, and gelation kinetics to support the right shape and mechanical properties of the printed construct. To this end, a facile design of thermo/photo dual cure composite hydrogel was proposed using MHBC and soluble collagen in this study. M/C composite hydrogel exhibited rapid thermo-induced sol-gel transition and contraction, tunable mechanical properties, proper microstructure and biodegradability for 3D cell culture, as well as improve cyto-compatibility, all of which were dependent upon the methacrylation degree of MHBC and M/C ratios. The printability of the optimal formulation (3% MHBC/1% collagen) was validated by its mild printing condition, rapid gelation of bioink at 37 °C and simple postprocessing manipulation. Both desirable printability and cyto-compatibility enable M/C composite hydrogel a potential candidate as bioink to be applied for in situ 3D bioprinting. • The composite hydrogel was prepared by thermo/photo dual cure. • The composite hydrogel formed rapidly under room temperature by sol-gel transition. • The composite hydrogel provided RGD motif to significantly enhance cell adhesion. • The composite hydrogel exhibited desirable printability and biocompatibility. • The composite hydrogel could be a potential bioink for in situ 3D bioprinting. [ABSTRACT FROM AUTHOR]