Medicated and multifunctional composite alginate-collagen-hyaluronate based scaffolds prepared using two different crosslinking approaches show potential for healing of chronic wounds.

Chronic wounds present significant challenges with high morbidity and mortality. A cost-effective dressing that can absorb large exudate volumes, is hemostatic and therapeutically active is of current interest. This study compares two crosslinking approaches on composite scaffolds comprising fish collagen (FCOL), hyaluronic acid (HA) and sodium alginate (SA) by respectively targeting HA and SA. Crosslinking involved reacting HA with polyethylene glycol diglycidyl ether (PEGDE)/itaconic acid (IT) (IPC scaffolds) or SA with calcium chloride (CC scaffolds) and the crosslinked gels (with/without BSA) freeze-dried. Selected optimized formulations were loaded with basic fibroblast growth factor (b-FGF) as medicated scaffold dressings. NMR and FTIR spectroscopies (crosslinking/component interactions), SEM (morphology), texture analysis (mechanical strength/adhesion), and exudate handling were used to characterize the physico-chemical properties of the scaffolds. Protein (BSA) release profiles, hemostasis, biocompatibility and wound closure were assessed using HPLC, whole blood and methyl thiazolyl tetrazolium (MTT) and scratch assays respectively. The CC SA:FCOL:HA scaffolds showed improved mechanical strength, porosity, water vapor transmission rate, retained structural integrity after absorbing 50% exudate and promoted cell proliferation. The IPC scaffolds showed enhanced structural integrity, excellent hemostasis, retained three times more exudate than non-crosslinked scaffolds and provided acceptable pore size for cell adhesion and proliferation. The results show potential of CC and IPC SA:FCOL:HA scaffolds as medicated dressings for delivering proteins to chronic wounds. The study's significance lies in their potential use as multifunctional, multi-targeted and therapeutic dressings to overcome challenges with chronic wounds and use as delivery platforms for other therapeutic agents for chronic wound healing.