D-ribose-loaded hydrogel modulates necrosis progression and wound stability in a rabbit random-pattern skin flap model

Background Random-pattern skin flaps remain highly susceptible to ischemic injury, resulting in progressive distal necrosis and wound instability. Early metabolic failure is a central component of ischemia–reperfusion injury in flap tissue. D-ribose, a pentose sugar involved in adenine nucleotide and adenosine triphosphate (ATP) resynthesis, may support metabolic recovery in ischemic environments. This study investigated whether local delivery of a D-ribose-loaded hydrogel modulates necrosis progression and wound stability in a rabbit random-pattern skin flap model. Methods Twenty-six adult male New Zealand White rabbits were randomly assigned to receive either a D-ribose-loaded chitosan hydrogel or an identical ribose-free control. A standardized caudally based random-pattern dorsal skin flap was elevated in each animal. Flap necrosis percentage, absolute necrotic area, and wound dehiscence were assessed using standardized digital imaging on postoperative days 3, 7, 9, 11, and 14. Flap failure was defined as development of ≥50% necrosis. Longitudinal changes were analyzed using linear mixed-effects modeling, while time-to-event outcomes were evaluated using Kaplan–Meier analysis with Cox regression. Dehiscence outcomes were analyzed using logistic regression and analysis of covariance. Results D-ribose hydrogel significantly modulated the temporal progression of flap necrosis, with a distinct group × time interaction compared with controls (p = 0.038). Treatment delayed progression to flap failure, increasing the median time to ≥50% necrosis from 7 to 11 days (hazard ratio 0.38; 95% CI 0.17–0.85; p = 0.018). Wound dehiscence occurred less frequently in the D-ribose group than in controls (15.4% vs. 61.5%; odds ratio 0.12; 95% CI 0.02–0.78; p = 0.015), and dehiscence areas were significantly smaller. Mean necrosis percentage correlated positively with dehiscence extent (Spearman's ρ = 0.68; p < 0.001). Conclusion Local delivery of a D-ribose-loaded hydrogel modulated necrosis progression and improved wound stability in a rabbit random-pattern skin flap model. These findings support metabolically active hydrogel-based strategies as a promising adjunct to enhance flap reliability under ischemic conditions.