Calcium-doped, curcumin-loaded zeolitic imidazolate framework-8 (ZIF-8) nanocomposites embedded in chitosan–egg albumin cryogels for enhanced wound healing: Synthesis, characterization, and biological evaluation

In this study, we developed a biocompatible, bioresorbable, and super-macroporous cryogel-based wound dressing via Schiff base crosslinking between chitosan and egg albumin. To impart multifunctionality, a nanocomposite of calcium-doped, curcumin-loaded zeolitic imidazolate framework-8 (Ca@CUR–ZIF-8) was incorporated into the cryogel matrix. Curcumin, a hydrophobic polyphenol, was successfully encapsulated within ZIF-8 to enhance its solubility and bioavailability. Encapsulation was confirmed by a redshift in Ultraviolet-Visible spectrophotometry (UV–Vis) absorption (from 425 nm to 441 nm) and further validated by Fourier Transform Infrared spectroscopy (FTIR), indicating non-covalent interactions within the framework. The Ca@CUR–ZIF-8 nanocomposite was uniformly distributed in the cryogel, enabling sustained, pH-responsive drug release that followed the Higuchi kinetic model. Mechanical testing showed enhanced structural integrity with a compressive strength of 0.138 ± 0.75 MPa and a Young's modulus of 0.1708 ± 0.205 MPa. In vitro cytocompatibility studies with 3T3 fibroblasts demonstrated >90% cell viability on days 5 and 7, highlighting the scaffold's non-toxic and extracellular matrix (ECM)-mimetic nature. In vivo experiments using Sprague–Dawley rat models revealed accelerated wound closure in the Ca@CUR–ZIF-8-treated group within 21 days, supported by histological evidence of enhanced granulation tissue formation. Hydroxyproline quantification indicated robust collagen deposition on day 7 (14.6 ± 0.17 μg/mg), followed by an increase on day 14 (16.41 ± 0.2 μg/mg), suggesting active tissue remodeling. Overall, the integration of Ca@CUR–ZIF-8 into a chitosan–egg albumin cryogel offers a promising platform for wound healing applications, combining mechanical strength, bioactivity, and controlled curcumin delivery, with strong potential for clinical translation in tissue regeneration.