From Bedside to Bench and Back: Advancing Our Understanding of the Pathophysiology of Cleft Palate and Implications for the Future.

OBJECTIVE: To provide a comprehensive understanding of the pathophysiology of cleft palate (CP) and future perspectives.

DESIGN: Literature review.

SETTING: Setting varied across studies by level of care and geographical locations.

INTERVENTIONS: No interventions were performed.

MAIN OUTCOME MEASURE(S): Primary outcome measures were to summarize our current understanding of palatogenesis in humans and animal models, the pathophysiology of CP, and potential future treatment modalities.

RESULTS: Animal research has provided considerable insight into the pathophysiology, molecular and cellular mechanisms of CP that have allowed for the development of novel treatment strategies. However, much work has yet to be done to connect our mouse model investigations and discoveries to CP in humans. The success of innovative strategies for tissue regeneration in mice provides promise for an exciting new avenue for improved and more targeted management of cleft care with precision medicine in patients. However, significant barriers to clinical translation remain. Among the most notable challenges include the differences in some aspects of palatogenesis and tissue repair between mice and humans, suggesting that potential therapies that have worked in animal models may not provide similar benefits to humans.

CONCLUSIONS: Increased translation of pathophysiological and tissue regeneration studies to clinical trials will bridge a wide gap in knowledge between animal models and human disease. By enhancing interaction between basic scientists and clinicians, and employing our animal model findings of disease mechanisms in concert with what we glean in the clinic, we can generate a more targeted and improved treatment algorithm for patients with CP.