Comparative analysis of chemical and physical cross-linking strategies for CMCs/Gelatin/PVA wound dressings: Balancing mechanical strength with biocompatibility

Abstract

In skin tissue engineering, the cross-linking of wound dressings is a critical step as it enhances mechanical strength. This improved strength regulates the release of incorporated components and determines the dressing’s replacement schedule. Therefore, due to the lack of comparative knowledge for the cross-linking of carboxymethyl chitosan, gelatin, and polyvinyl alcohol (CMCs-Gel-PVA) wound dressings, this study was designed a systematic comparison of five distinct strategies: chemical cross-linkers—glutaraldehyde (GLU), EDC/NHS, citric acid (CA), and succinic acid (SA)—alongside a physical freeze-thaw method. Cross-linked wound dressings were fabricated and systematically characterized in terms of surface morphology (SEM), chemical bonding (FTIR), mechanical strength, porosity, biodegradability, fluid absorption, blood compatibility, cytotoxicity, and anti-inflammatory activity. The scaffolds exhibited interconnected pores ranging from 32.07 to 89.12 µm. The non-cross-linked sample showed higher porosity, liquid absorption, and degradation rate (90.33 ± 5.17%), which was attributed to its lower mechanical strength. All samples demonstrated good biocompatibility with no significant cytotoxic effects on 3T3 fibroblasts. Tensile strength values ranged from 0.15 to 1.92 MPa. Glutaraldehyde-crosslinked scaffolds displayed superior mechanical properties suitable for load-bearing wound applications, despite a slight reduction in cell viability (92.59 ± 3.19%), which remained above the accepted clinical biocompatibility threshold. These scaffolds also showed enhanced coagulation activity, whereas citric acid-crosslinked samples exhibited anticoagulant behavior and superior anti-inflammatory potential. In conclusion, this comparative study demonstrates that the choice of cross-linker dictates key functional properties of CMCs-Gel-PVA scaffolds, allowing for the strategic tuning of mechanical strength, degradation rate, hemostatic activity, and anti-inflammatory potential. These tailored in vitro characteristics support their further investigation as candidate materials for advanced wound dressing applications. The successful in vivo validation of these findings remains a critical next step to fully ascertain the translational potential of this biomaterial platform.