Comparison of the effects of human fetal umbilical cord-derived hyaluronic acid and fibroblast-derived exosomes on wound healing in rats

Exosomes and hyaluronic acid influence tissue regeneration and may be used as an alternative to more conventional wound treatment methods. This study compared how well hyaluronic acid from the human umbilical cord and exosomes from fibroblast cells heal burn wounds in a preclinical model. Ninety-six male Westar rats were used and allocated into four groups: The treatment group received 10% hyaluronic acid (HA); the treatment group received 300 l of exosome solution (EX); the treatment group received phenytoin (PC); the negative control group received no treatment (NC). The wound healing process was evaluated after 3, 6, 9, and 12 days. Histopathological analysis was done on the skin biopsy taken from the wounds. Re-epithelialization, inflammatory cells (PMNs), lymphocytes (LYMs), granulation tissue, collagen maturation (fibrosis), and eschar formation parameters were assessed for histopathological evaluation. On a scale from 0 to 4, each parameter received a score. Compared to the PC and NC groups, the median score for re-epithelialization was greater in the HA and EX groups (P < 0.05). At three days, PMN abundance distinguished the PC and NC groups from the HA and EX groups (P < 0.01). Compared to the PC and NC groups, the HA and EX groups had a lower median LYM score (P < 0.01). We found no statistical difference between the four groups for granulation tissue and fibrosis (P > 0.05). The EX group had a lower average score for eschar formation than the PC, NC, and HA groups (P < 0.01). The HA and EX groups demonstrated faster healing in the clinical and microscopic examinations than the NC and PC groups. The results showed that hyaluronic acid and exosomes improved wound healing. Also, the study demonstrated that hyaluronic acid has better effects in the re-epithelization. The exosome was more effective than HA in eschar formation. Both compounds were more influential in the PMNs and LYMs parameters than other groups. The combination of both compounds should be assessed further to achieve better therapeutic effects on wound healing.