Polycation-stabilized alginate-based hydrogels for the regeneration of skin and mucous membranes

Due to their favorable physicochemical and rheological properties, sodium alginate (SA)-based hydrogels are widely used as matrices for wound-healing dressings. Modification of alginate hydrogels with polycations, particularly PAMAM dendrimers, enables the formation of stable polyelectrolyte complexes and creates platforms for the immobilization and controlled release of bioactive compounds. Incorporation of porphyrins acting as superoxide dismutase (SOD) mimetics may reduce reactive oxygen species and oxidative stress and limit fibrous tissue formation. Therefore, this study aimed to evaluate polycation-stabilized SA hydrogels containing a porphyrin SOD mimetic as bioactive systems for wound healing and tissue regeneration.

The study utilized high-molecular-weight SA, third- and fourth-generation PAMAM dendrimers (G3 and G4), and Mn(III)TnHex-2-PYP (TPyp). Potentiometric titration showed a high degree of protonation of PAMAM primary amino groups at pH 7.4, reaching 98% for G3 and 85.53% for G4, confirming their cationic activity and ability to complex with SA. Formation of SA-PAMAM polyelectrolyte complexes was confirmed by FTIR spectroscopy and UV spectrophotometry. The possibility of incorporating TPyp into G3 and G4 dendrimers was subsequently investigated. Porphyrin release kinetics and the effects of the nature and concentration of calcium chloride and calcium sulfate crosslinkers on release from SA-PAMAM hydrogels were evaluated; the maximum released fraction reached 96.8%.

The biological properties of the developed hydrogel systems were then assessed. The hydrogels showed no significant cytotoxicity toward HaCaT keratinocytes and BJ-5ta fibroblasts. Under induced oxidative stress, treatment with hydrogel extracts reduced the proportion of DCFDA-positive cells from 56.31% to 11.41% in HaCaT cells and from 54.55% to 1.85% in BJ-5ta cells. In addition, the TPyp-containing system promoted macrophage polarization toward the anti-inflammatory M2 phenotype, indicating a potential pro-regenerative effect.

These results confirm the feasibility of developing a biocompatible porphyrin-containing system based on polycation-stabilized sodium alginate for accelerated regeneration of skin and mucous membranes.