Chitosan and aloe vera-based biomaterials for wound healing applications

Abstract The complexity of wound healing, particularly for chronic wounds, necessitates advanced dressings that actively modulate the wound microenvironment. This work critically evaluates the synergistic integration of chitosan (CS) and aloe vera (AV) into advanced wound dressings. Chitosan offers a biocompatible, biodegradable, antimicrobial, and hemostatic scaffold, while Aloe vera contributes potent anti-inflammatory, antioxidant, moisturizing, and pro-regenerative biomaterials. While single-component products based on CS (e.g., MaxioCel®) or AV (e.g., Acemannan hydrogel) are clinically established, hybrid CS–AV systems present distinct synergistic advantages across multiple phases of tissue repair. The review details innovative formulations, including hydrogels, nanofibers, 3D-printed structures, films, and sponges, highlighting advancements in crosslinking, functional additives (e.g., antimicrobials, growth factors), and fabrication techniques. Mechanistically, CS-AV synergy manifests through enhanced antimicrobial efficacy, potent anti-inflammatory and antioxidant effects via modulation of cytokine profiles and ROS scavenging, stimulation of cellular proliferation and migration (fibroblasts, keratinocytes), and positive influence on extracellular matrix (ECM) remodeling, potentially leading to reduced scar formation. Preclinical evidence consistently demonstrates accelerated wound closure, improved re-epithelialization, enhanced angiogenesis, and superior tissue quality in various animal models. However, substantial translational challenges remain regarding raw material standardization (CS molecular weight/deacetylation degree and AV acemannan quantification), residual crosslinker safety, and a lack of randomized clinical trials. This review critically balances the promising preclinical efficacy of CS–AV composites with the rigorous standardization, GLP toxicological profiling, and clinical frameworks required for bench-to-bedside translation.