Physically and Chemically-Crosslinked L-arginine-loaded Polyvinyl Alcohol- Hyaluronic Acid- Cellulose Nanocrystals Hydrogel Membranes for Wound Healing: Influence of Crosslinking Methods on Biological Performance of Membranes In-Vitro

Two types of polyvinyl alcohol-blended hyaluronic acid and cellulose nanocrystals (PVA/HA/CNCs) hydrogels membranes were developed as delivery agents for L-arginine using chemical/and/physical crosslinking methods for exploring biological performance of the obtained membranes. Chemically and physically/crosslinked membranes were fabricated by solution-casting and freeze-thawing techniques, respectively. The characterization of the crosslinked PVA/HA/CNCs/L-arginine membranes were conducted by SEM, FTIR, TGA, swelling ratio, and in—vitro L-arginine release. Furthermore, applying two types of crosslinked membranes in vitro were investigated in terms of cytotoxicity, hemocompatibility, and cell adhesion affinity of HFB-4 cell line. Chemical and physical-crosslinked membranes were verified through the esterification and hydrogen bonds interactions, respectively as shown the FTIR spectra. The chemically-crosslinked membranes showed more thermal and mechanical stability than the physically-crosslinked ones. Besides, the chemically-crosslinked hydrogels exhibited biphasic release behavior of L-arginine reached 50% in the first hour and 92% after 48 h. Notably, chemically-crosslinked membranes a somewhat affect the cell viability %, while both crosslinked membranes exhibited excellent cell adhesion affinity and low hemolysis. However, the physically- crosslinked members showed high cell viability ~ 172%, compared to the chemically-crosslinked membranes at 98.5%; and low hemolysis ca . 0.84 versus 1.34 for chemically-crosslinked membranes. Accordingly, both types of crosslinked membranes have a potential for applying in biomedical applications, particularly for designing promising wound dressing biomaterials.