Optimizing the Host Niche to Fuel Cleft Lip Muscle Regeneration

ObjectiveLip muscle reconstruction is a key strategy for cleft lip repair, but the outcome of muscle regeneration is suboptimal. The lack of relevant models restricts studies on cleft lip muscle regeneration.DesignIn this study, we developed an animal xenograft model by transplanting muscle samples from patients with cleft lip into different host sites in immunodeficient mice. The grafted muscles were harvested after 1, 2, and 5 months to investigate the temporal dynamics of myofiber growth and maturation. Comparisons were made among muscle biopsies, xenografts in the masseter (MAS) muscle of the mice, and xenografts in the tibialis anterior (TA) muscle of the mice to determine the optimal host niche.Main Outcome Measures:Histological analysis of myofiber number and size, fiber type switching, innervation, and blood supply was performed to evaluate the cleft lip muscle regeneration process.ResultsThe muscles from cleft lip patients underwent an active degeneration-regeneration cycle. The fiber diameter in the MAS niche was significantly larger than that in the TA niche and was comparable to the fiber diameter of the donor biopsy from which it originated. The innervation and blood supply of the muscle grafts at the MAS host site were also superior to those of the grafts at the TA host site.ConclusionsThe MAS muscles of mice provided the most favorable microenvironment for cleft lip muscle regeneration. This patient-centered xenograft model offers a platform for cleft lip muscle regeneration studies.