Comprehensive overview of biomaterials for bone regeneration in cleft lip and palate

Cleft lip and palate (CL/P) is the most common congenital malformation within the oral and maxillofacial region of human beings, involving abnormal development of lips, palate, and alveolar bone. Bone grafting is a crucial yet challenging part of the treatment for CL/P. Although autologous iliac bone transplantation is the clinical gold standard, additional surgical trauma, donor site complications, bone resorption, and risk of secondary surgical grafting undermine its clinical efficacy. Recently, synthetic bones have attracted increasing attention for bone regeneration, such as calcium phosphate bioceramics, because of their good biocompatibility, superior bioactivity, and outstanding osteoinductivity. However, their application in congenital bone defects, especially for patients in the developmental stage, is in urgent need of development, and the regenerative mechanisms require further detailed revelation. This review presents a comprehensive overview of recent advancements in biomaterials for congenital alveolar bone regeneration. It begins with an introduction to maxillofacial bone development, the pathological mechanisms of CL/P with alveolar clefts, and the current state of clinical bone grafting. Then, preclinical research of artificial bones for alveolar bone regeneration is systematically reviewed, and a specific comparative summary is conducted on reported preclinical research models that currently lack unified standards. Furthermore, the future perspectives and the requirements of artificial bones for congenital alveolar bone defects are proposed. This review may shed some light on the development of biomaterials for bone regeneration in congenital maxillofacial bone defects.