Abstract
Wound healing is frequently compromised under pathological conditions, necessitating the development of effective biomaterials capable of promoting tissue repair. This study evaluated the wound-healing potential of marine-derived chitosan nanoparticles (CSNPs) and chitosan–tripolyphosphate nanoparticles CSNPs-TP in a challenging model of impaired wound healing. Full-thickness skin wounds were experimentally induced, and animals were treated with CSNPs or CSNPs-TP while carbapol treated animals served as the control. Wound closure was monitored macroscopically over 17 days, and histopathological examination was performed on Days 7 and 17 to assess tissue regeneration and remodeling. Both nanoparticle formulations significantly accelerated wound closure compared with the Control group. At Day 3, wound closure reached 37.66 ± 6.99% and 55.05 ± 12.07% in the CSNPs and CSNPs-TP groups, respectively, compared with 11.88 ± 13.91% in the Control group. By Day 14, both nanoparticle-treated groups achieved more than 93% wound closure, compared with 59.37 ± 18.88% in the Control group. By Day 17, the CSNPs-TP group achieved complete wound closure (100.00 ± 0.00%), closely followed by CSNPs (99.61 ± 0.55%), whereas the Control group reached 79.88 ± 12.17%. Histopathological examination further demonstrated enhanced tissue regeneration in the nanoparticle-treated groups. CSNPs-TP particularly promoted granulation tissue formation, fibroblastic proliferation, and neovascularization at Day 7, followed by complete re-epithelialization, well-developed rete ridges, organized collagen deposition, and restoration of skin adnexa at Day 17. Overall, marine-derived chitosan nanoparticles, particularly CSNPs-TP, markedly enhanced wound closure and histological tissue regeneration, highlighting their potential as promising biomaterials for accelerating wound repair under challenging healing conditions.

Key words: Marine-derived chitosan; Chitosan nanoparticles; Chitosan–tripolyphosphate nanoparticles; Impaired wound healing; Tumor-bearing mice; Chemotherapy.