Introduction: Cleft palate is a congenital condition affecting the development of maxillofacial bones. Current treatment is based on the surgical repair of the soft tissues in order to generate a physical barrier between the oral and nasal cavities. However, this treatment is associated with subsequent bone hypoplasia and misdevelopment in most patients. In this regard, we recently generated a bioengineered model of the human palate mucosa using fibrin-agarose biomaterials that offered promising results in newborn rabbits1,2. These positive results allowed us to design an advanced therapies clinical trial (BIOCLEFT) in which autologous palate mucosa will be grafted in a group of patients at the moment of the surgical repair of the palate defect.
Methodology: First, small oral mucosa biopsies obtained at the moment of the cleft lip repair, are processed to generate primary cell cultures of keratinocytes and fibroblasts. Then, bioengineered substitutes of the human palate mucosa are generated using fibrin hydrogels with 0.1% agarose.
Results: Application of the biofabrication methods optimized by the research group allow the efficient generation of palate mucosa substitutes in the laboratory. Palate mucosa substitutes generated by tissue engineering are viable and show structural similarities with native human palate, with a stroma substitute containing fibroblasts and a stratified epithelium on top. This palate mucosa substitute will be used to cover the maxillary bone defect of patients corresponding to the BIOCLEFT study group, whereas the standard surgical technique in which the bone defect is left uncovered is used in control patients. Results will be first analyzed in terms of feasibility and safety and then, in terms of improvement in craniofacial growth and development.
Conclusions: These bioengineered palate mucosa substitutes fulfil the criteria for use as ATMP for the regenerative treatment of children with cleft palate. The positive results obtained in laboratory animals in terms of biosafety and functionality support the putative beneficial effect of this technology in the BIOCLEFT clinical trial.