Cleft lip and cleft palate are the most prevalent congenital craniofacial defects in humans; they occur in about 1:700 live births worldwide. Incomplete formation of the upper lip (cleft lip) or roof of the mouth (cleft palate) may occur individually or concomitantly. Surgical repair of the lip and cleft palate is currently the clinical standard of care. The surgical interventions aim at the fusion of the palatal shelves and restoration of the function of the lips and mouth, however, none of the procedures currently used lead to a definitive correction. Severe defects are hard to correct with surgery only, resulting in complications and sequelae that require multidisciplinary, life-long care. 1 2 3
Advances in tissue engineering and regenerative medicine aim to offer new strategies to stimulate bone formation at the site of cleft lip and palate surgical correction. Those strategies can use different approaches based on the application of functional biomaterials, in association with the local delivery of bioactive regenerative molecules and guided or recruited stem cells. These bioactive molecules and stem cells can promote self-repair mechanisms in the affected tissues, improving the living conditions of patients. 4
Figure 1: Stem cells, scaffolds, and molecule signals as fundamental pieces of the tissue engineering triad for cleft/lip palate regeneration. 4
Recently, decellularized biomaterials from tissues or organs have emerged as a promising option to be used as scaffolds for the tissue engineering of body parts. The aim of a study by Rizzo et al. was to develop a new natural scaffold derived from a decellularized porcine mucoperiosteum and promote its in vitro recellularization with human bone marrow-derived mesenchymal stem cells. The ultrastructural analysis indicated that the decellularization procedure preserved the collagen mesh, increasing the osteoinductive potential of the mesenchymal precursor cells, which can facilitate mucosal and bone regeneration, maintenance, and reduction of immunogenicity. 5
Figure 2: Representative images of (a) non-decellularized and (b) decellularized hemi-palates. 5
Some clinical trials are already using tissue engineering to reconstruct alveolar bone defects in patients with cleft lip and palate. In Brazil, a study that took place at Hospital Sirio-Libanês included five patients with unilateral cleft lip and palate to undergo alveolar bone tissue engineering surgery. The selected patients had previously undergone alignment of the dental arches through orthodontic treatment. The clinical team performed secondary alveolar grafts in patients using mesenchymal stem cells obtained from the dental pulp of deciduous teeth associated with a biomaterial composed of collagen and hydroxyapatite. The treatment was able to eliminate the pain and morbidity of the bone donor region (iliac crest) that would be necessary for a traditional surgical procedure, as well as reduce hospitalization time and costs for the healthcare system (NCT01932164). 6
REFERENCES
1. American society of plastic surgeons. https://www.plasticsurgery.org/reconstructive-procedures/cleft-lip-and-palate-repair.
2. Panetta, N. J. et al. Tissue engineering in cleft palate and other congenital malformations. Pediatr. Res. 63, 545–551 (2008).
3. Oliver, J. D. et al. Innovative Molecular and Cellular Therapeutics in Cleft Palate Tissue Engineering. Tissue Eng. Part B Rev. 27, 215–237 (2021).
4. Martín-del-Campo, M., Rosales-Ibañez, R. & Rojo, L. Biomaterials for Cleft Lip and Palate Regeneration. Int. J. Mol. Sci. 20, 2176 (2019).
5. Rizzo, M. I. et al. Engineered mucoperiosteal scaffold for cleft palate regeneration towards the non-immunogenic transplantation. Sci. Rep. 11, 14570 (2021).
6. Use of Mesenchymal Stem Cells for Alveolar Bone Tissue Engineering for Cleft Lip and Palate Patients. https://clinicaltrials.gov/ct2/show/NCT01932164?term=tissue+engineering&cond=Cleft+Palate&draw=2&rank=1.