Retinoic acid enhances the effect of collagen on bone union, following induced non-union defect in guinea pig ulna

Objective and Design: The aim of the present study is to evaluate the involvement of retinoic acid and collagen in wound healing, by combining them in a therapeutic modality for treating a non-union bone defect in a guinea-pig ulnar-bone model. Methods: a 4-mm disc was excised from the guinea-pig's ulnar-bone, and the space formed between the two ulnar fragments was filled with either collagen solution, retinoic acid solution or a combination of both. The guinea-pigs were sacrificed 2 or 6 weeks later, and the defected ulnar bones were studied by X-ray, by histology and by computerized histomorphometry. Results: After 6 weeks, the long bone area fraction within the histological sections of the bone, was increased after treatment with this mixture by 180%, as compared to the untreated controls. The cartilage area in those sections was decreased by 44% after the combined treatment, as compared to increases of 133% and 182% following treatments with collagen alone. Conclusion: These findings demonstrate that addition of 500 IU of retinoic acid to collagen at a site of a bone defect, is superior to either agent in enhancing regeneration of new bone, achieving union across the defect and leading to its complete repair.