Engineering Metal–Organic Framework-Biopolymer-Based Hydrogels for Therapeutic Delivery

Biopolymer-based hydrogels are attractive therapeutic carriers, offering tunable physicochemical properties and therapeutic release kinetics. Major limitations include low rheological strength, poor physical and thermal stability, limited swelling, and achieving controlled therapeutic delivery. To address these challenges, a library of innovative metal-organic framework (MOF)-biopolymer-based hydrogels was developed. The MOFs, zeolitic imidazole framework-8 (ZIF-8), and zinc adeninate framework (ZAF) were integrated into chitosan/alginate (C/A) and chitosan/gelatin (C/G) hydrogels, at increasing chitosan content. The MOF-hydrogels presented distinct immunoglobulin G (IgG) release rates and greater rheological strengths, swelling capabilities, and thermostabilities compared to the MOF lacking hydrogels. The MOF-C/A-hydrogels showed higher rheological strengths compared to the MOF-C/G-hydrogels. The ZIF-8-hydrogels presented greater rheological strengths, yet lower thermostabilities, and higher IgG release rates compared to the ZAF-hydrogels. This is attributed to the greater flexibility of ZAF, containing bulky adenine groups, which could lead to steric hindrance and limited zinc ion-dipole interactions. Holistically, exploiting ion-dipole, electrostatic, and hydrogen bonding interactions between the MOFs and biopolymers enabled therapeutic release rate control and balanced the typical trade-off between hydrogel swelling and rheological strength. The MOF-hydrogels offer adaptable platforms, advancing the design of next-generation MOF-biopolymer-based carriers for target applications.