**Author details**

**2.7. Remaining mouse strains exhibiting CL/P phenotype**

efficacy, and some are showing promising results thus far.

its potential to replace traditional autogenous grafting procedures [27].

humans.

**2.8. The future of CL/P therapy**

138 Designing Strategies for Cleft Lip and Palate Care

Here, we have put into one table a list of the genes with a known association, whether syndromic or non-syndromic, to the development of the palate in mouse (**Table 1**). It should be noted that not all genes in this table have shown their identical, cross species phenotype in

A bonafide surgical protocol remains to be standardized for the repair of CL/P. Fortunately, ongoing research concerning therapeutic interventions for this relatively common birth defect has recently begun to delve into new and improved options for repair with, hopefully, more consistent and stable results for patients. The current "golden standard" treatment option for pediatric oral surgeons involves bone grafting, or alveoloplasty, usually from autogenous sites—but this has many complications associated with both the grafting procedure and the agreed-upon effectiveness in reconstructing the palate over time [21]. Postoperative followup has shown success rates ranging from 41 to 73%, which is far from standardized, while there also exists the possibility (in 11–23% of patients) of oronasal fistulas, which come with their own brand new set of complications for the patient [22]. In short, the most effective interventions in use today are far from ideal for the patent and result in long-term risk of complications from grafting procedures, disturbance of adjacent craniofacial development, and, over time, a significant financial encumbrance on the patient. Techniques including gene delivery, in vitro engineered tissue transplantation, and regenerative medicine are being probed for

An exceptionally exciting modality is the use of stem cells. One method of delivering these cells is via a biocompatible scaffold upon which cells that have been previously harvested were cultured and attached. Materials including collagen, hyaluronic acid, and hydroxyapatite have been utilized in attempts to develop such scaffolds [23–25]. These scaffolds have been engineered as injectable gels, mesh networks, and foams. Ideally, this aids in the procedure being as minimally invasive as possible while also providing maximum benefit and adequate delivery to the area of interest. This therapy can be modified to include signaling molecules and other types of differentiated cells—which preferably have a known clinical outcome and avoid the possibility of rejection and/or disunity with the surrounding host cells—and injected in a similar fashion or applied to previously engineered palates. Currently, autogenous mesenchymal stem cells (MSCs) are regarded as the optimum choice for in vivo osteogenic reconstructions; these can come from umbilical cord blood, Wharton's jelly, and even the patient's own bone marrow [26]. Tissue regenerative-specific repair of CL/P has been demonstrated with some success, and some are now advocating for in depth considering of

Regarding clinical studies in progress, one group has shown that in vitro differentiated MSCs derived from bone marrow were delivered with platelet-derived growth factor and significant improvement was observed 3 months post-op [28]. Similarly, recombination therapies are being used to induce osteoblastic differentiation with BMPs formed from stem cells, and resulting immunohistological analysis of the bone that formed has shown normal, vital Aram J. Keteyian\* and Yuji Mishina

\*Address all correspondence to: aketeyia@umich.edu

Department of Biologic and Materials Science, School of Dentistry, University of Michigan, Ann Arbor, MI, USA
