Aellos Fabiana, Verma Ishita, Ly Melody, Hoy Mackenzie, Quach Tom, Rosbander Isabel, Sandoval Alejandro, Wolvis Eppo, Turkkahraman Hakan, Helms Jill A
Department of Surgery, Stanford University School of Medicine, Stanford, CA.
Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
J Craniofac Surg. 2024 Nov 4;36(3):876-81. doi: 10.1097/SCS.0000000000010827.
To quantitatively assess the impact of early versus late surgical intervention on midfacial growth using a mouse model.
A full-thickness mucoperiosteal flap surgery was performed on newborn (P17) mice and on neonatal (P30) mice. High-resolution micro-computed tomographic imaging coupled with histomorphometric analyses was used to assess craniomaxillofacial growth. Histology and immunohistochemical analyses were used to assess cellular and molecular responses postsurgery.
Early surgical intervention at P17 resulted in significant midfacial growth arrest, with pronounced maxillary hypoplasia. Histomorphometric analyses revealed significant (P < 0.05) growth disruptions in the mid-palatal suture complex, including premature removal of the cartilaginous growth plate and its replacement by bone. In the suture itself, cell proliferation was significantly reduced (P < 0.05) compared with controls. The same surgical intervention performed in mice at P30 did not lead to significant midfacial growth arrest.
Early surgical intervention in a mouse model mirrors the adverse growth outcomes in children undergoing early cleft repair. Molecular and cellular observations accompanying this midfacial growth arrest may inform therapeutic strategies to mitigate midfacial growth disturbances in patients and highlight the need for refined surgical techniques to minimize adverse growth outcomes.
使用小鼠模型定量评估早期与晚期手术干预对中面部生长的影响。
对新生(P17)小鼠和幼鼠(P30)进行全层黏骨膜瓣手术。采用高分辨率微计算机断层扫描成像结合组织形态计量学分析来评估颅颌面生长。组织学和免疫组织化学分析用于评估术后细胞和分子反应。
P17时的早期手术干预导致明显的中面部生长停滞,上颌发育不全明显。组织形态计量学分析显示,腭中缝复合体存在显著(P < 0.05)的生长破坏,包括软骨生长板过早去除并被骨替代。在缝线本身,与对照组相比,细胞增殖显著减少(P < 0.05)。在P30的小鼠中进行相同的手术干预未导致明显的中面部生长停滞。
小鼠模型中的早期手术干预反映了早期唇腭裂修复儿童的不良生长结局。伴随这种中面部生长停滞的分子和细胞观察结果可能为减轻患者中面部生长紊乱的治疗策略提供信息,并突出需要改进手术技术以尽量减少不良生长结局。