Med Res Rev. 2020 Jan;40(1):9-26. doi: 10.1002/med.21594. Epub 2019 May 18.

Tissue Engineering Strategies Combining Molecular Targets Against Inflammation and Fibrosis, and Umbilical Cord Blood Stem Cells to Improve Hampered Muscle and Skin Regeneration Following Cleft Repair

Michaël Schreurs  ¹ , C Maarten Suttorp  ^{1   2} , Henricus A M Mutsaers  ³ , Anne Marie Kuijpers-Jagtman  ⁴ , Johannes W Von den Hoff  ^{1   2} , Edwin M Ongkosuwito  ¹ , Paola L Carvajal Monroy  ⁵ , Frank A D T G Wagener  ^{1   2}

Abstract

Cleft lip with or without cleft palate is a congenital deformity that occurs in about 1 of 700 newborns, affecting the dentition, bone, skin, muscles and mucosa in the orofacial region. A cleft can give rise to problems with maxillofacial growth, dental development, speech, and eating, and can also cause hearing impairment. Surgical repair of the lip may lead to impaired regeneration of muscle and skin, fibrosis, and scar formation. This may result in hampered facial growth and dental development affecting oral function and lip and nose esthetics. Therefore, secondary surgery to correct the scar is often indicated. We will discuss the molecular and cellular pathways involved in facial and lip myogenesis, muscle anatomy in the normal and cleft lip, and complications following surgery. The aim of this review is to outline a novel molecular and cellular strategy to improve musculature and skin regeneration and to reduce scar formation following cleft repair. Orofacial clefting can be diagnosed in the fetus through prenatal ultrasound screening and allows planning for the harvesting of umbilical cord blood stem cells upon birth. Tissue engineering techniques using these cord blood stem cells and molecular targeting of inflammation and fibrosis during surgery may promote tissue regeneration. We expect that this novel strategy improves both muscle and skin regeneration, resulting in better function and esthetics after cleft repair.