Forging a New Path in Cleft Rehabilitation by Tissue Engineering – A Review
Science Journal of Clinical Medicine
Volume 5, Issue 4-1, July 2016, Pages: 7-13
Received: Dec. 23, 2015; Accepted: Feb. 23, 2016; Published: Apr. 16, 2016
Views 3259      Downloads 94
Rohit Raghavan, Department of Prosthodontics, Royal Dental College, Chalissery, Palakkad, Kerala
Sumitra S., Department of Prosthodontics, Royal Dental College, Chalissery, Palakkad, Kerala
Nadeem Abdul Rahman, Department of Prosthodontics, Royal Dental College, Chalissery, Palakkad, Kerala
Justin Baby, Department of Prosthodontics, Royal Dental College, Chalissery, Palakkad, Kerala
Article Tools
Follow on us
Of all the birth defects, Cleft palate is among the most common and affects about one in 1,500 births resulting in medical, physical, developmental, social and emotional problems in affected children in addition to the high health care costs. Current treatment is based on surgical closure of the cleft followed by orthodontic dental care, speech therapy, bone grafting, and requires multiple surgeries spanning over 18 years. Thus, there is a pressing need to develop more effective methods of treatment to provide young patients with a safer option that will result in a complete closure of the palatal cleft shortly after birth. In this review, the application of the field of tissue engineering, involving the use of adult stem cells, such as mesenchymal stem cells from bone marrow and Adipose-derived Stem Cells (ASCs) seeded on currently available biomaterials is presented in the context of healing craniofacial defects like the cleft palate. This article presents the concise technique to generate new bone in cleft deformities, using stem cells. It also throws light on the work done by various researchers to regenerate bone in large defects.
Bone Tissue Engineering, Cleft, Stem Cells, Growth Factors, Scaffolds
To cite this article
Rohit Raghavan, Sumitra S., Nadeem Abdul Rahman, Justin Baby, Forging a New Path in Cleft Rehabilitation by Tissue Engineering – A Review, Science Journal of Clinical Medicine. Special Issue:Clinical Conspectus on Cleft Deformities. Vol. 5, No. 4-1, 2016, pp. 7-13. doi: 10.11648/j.sjcm.s.2016050401.12
Copyright © 2016 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Sameh A. Seifeldin, “Is alveolar cleft reconstruction still controversial? (Review of literature)” The Saudi Dental Journal (2015).
P. J. Boyne and N. R. Sands, “Secondary bone grafting of residual alveolar and palatal clefts” Journal of Oral Surgery, Vol. 30, no. 2, pp. 87–92, 1972.
Motoko Yoshioka, Kotaro Tanimoto, Yuki Tanne, Keisuke Sumi, Tetsuya Awada, Nanae Oki, Masaru Sugiyama, Yukio Kato, and Kazuo Tanne, “Bone Regeneration in Artificial Jaw Cleft by Use of Carbonated Hydroxyapatite Particles and Mesenchymal Stem Cells Derived from Iliac Bone”.
M. F. Pittenger, A. M. Mackay, S. C. Beck et al., “Multilineage potential of adult human mesenchymal stem cells” Science, Vol. 284, no. 5411, pp. 143–147, 1999.
M. Gimbel, R. K. Ashley, M. Sisodia et al., “Repair of alveolar cleft defects: reduced morbidity with bone marrow stem cells in a resorbable matrix,” Journal of Craniofacial Surgery, Vol. 18, no. 4, pp. 895–901, 2007.
Anil Dhingra, Shalya Raj, Tissue Engineering In Endodontics, Int. Journal of Clinical Dental Science, February, 2011 • 2(1).
M. Sujesh, V. Rangarajan, C. Ravi Kumar, and G. Sunil Kumar, “Stem Cell Mediated Tooth Regeneration: New Vistas in Dentistry” Journal of Indian Prosthodontic Society 2012 March; 12(1): 1–7.
Nakashima M, Mizunuma K, Murakami T, Akamine A. “Induction of dental pulp stem cell differentiation into odontoblasts by electroporation-mediated gene delivery of growth/differentiation factor 11” (Gdf11) Gene Ther. 2002; 9(12): 814–818. doi: 10.1038/]
Yarlagadda, MargamChanrasekhakaran, “Recent advances and current developments in tissue scaffolding” Biomedical materials and engineering 2005 15 (3)].
Ni- Hung Lin & Mark Bartold “Stem cells & periodontal regeneration”Periodontology 2000, Vol 51, 2009.
PATRICIA A. ZUK “Tissue Engineering Craniofacial Defects with Adult Stem Cells? Are We Ready Yet?. Pediatric research.Vol. 63, No. 5, 2008.
Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. “Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo” Proc Natl AcadSci USA. 2000; 97: 13625–13630. doi: 10.1073/pnas.240309797.
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, et al. “Multilineage potential of adult human mesenchymal stem cells” Science. 1999; 284: 143–147. doi: 10.1126/science.284.5411.143.
Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV 1966 “Osteogenesis in transplants of bone marrow cells” J Embryol Exp Morphol 16: 381–390.
Grigoriadis AE, Heersche JN, Aubin JE“Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone-derived clonal cell population: effect of dexamethasone” J Cell Biol 1988 106: 2139–2151.
Haynesworth SE, Goshima J, Goldberg VM, Caplan AI “Characterization of cells with osteogenic potential from human marrow” 1992 13: 81–88.
Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP 1997 “Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro” J Cell Biochem 64: 295–312.
Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU 1998” In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells”Exp Cell Res 238: 265–272.
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR 1999 “Multilineage potential of adult human mesenchymal stem cells” Science 284: 143–147.
Wakitani S, Saito T, Caplan AI 1995 “ Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine” Muscle Nerve 18: 1417–1426.
Pompilio G, Cannata A, Peccatori F, Bertolini F, Nascimbene A, et al. “Autologous peripheral blood stem cell transplantation for myocardial regeneration: a novel strategy for cell collection and surgical injection” Ann Thorac Surg. 2004; 78: 1808–1812. doi: 10.1016/j.athoracsur.2003.09.084.
De Ugarte DA, Morizono K, Elbarbary A, Alfonso Z, Zuk PA, et al. “Comparison of multi-lineage cells from human adipose tissue and bone marrow” Cells Tissues Organs.2003; 174: 101–109. doi: 10.1159/000071150.
Rodriguez AM, Elabd C, Amri EZ, Ailhaud G, Dani C. “The human adipose tissue is a source of multipotent stem cells” Biochimie. 2005; 87(1): 125–128. doi: 10.1016/j.biochi.2004.11.007.
Estes BT, Wu AW, Guilak F. “Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein”. Arthritis Rheum. 2006; 54(4): 1222–1232. doi: 10.1002/art.21779.
Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, et al. “Human adipose tissue is a source of multipotent stem cells.” MolBiol Cell. 2002; 13: 4279–4295. doi: 10.1091/mbc.E02-02-0105.
Peptan IA, Hong L, Mao JJ. “Comparison of osteogenic potentials of visceral and subcutaneous adipose-derived cells of rabbits.” PlastReconstr Surg. 2006; 117: 1462–1470. doi: 10.1097/01.prs.0000206319.80719.74.
Gimble JM, Guilak F. “Differentiation potential of adipose derived adult stem (ADAS) cells.” Curr Top Dev Biol. 2003; 58: 137–160. doi: 10.1016/S0070-2153(03)58005-X.
Luisa F. Echeto, Ingeborg J. De Kok, Debra Sacco, Susan J. Drapeau, and Lyndon F. Cooper. Enliven. “Peri-implant Alveolar Bone Augmentation Using Allogeneic Marrow-Derived Stem Cells; A Pilot Study in the Canine Mandible.” Journal of Genetic, Molecular and Cellular Biology.2014 | Volume 1 | Issue 1.
PetarZivokovic. “Stem cell based dental tissue engineering.” The scientific world journal.2010. Vol 10.
Stevenson S 1998. “Enhancement of fracture healing with autogenous and allogeneic bone grafts.” Clin Orthop Relat Res S239–S246.
Urist MR 1965. “Bone: formation by auto induction.” Science 150: 893–899.
Anil Dhingra, Shalya. “Tissue Engineering In Endodontics.” RIJCDS • FEBRUARY, 2011 • 2(1).
G. Pagni, D. Kaigler, G. Rasperini, G. Avila-Ortiz, R. Bartel, W. V. Giannobile. “Bone repair cells for craniofacial regeneration.” Advanced Drug Delivery Reviews 64 (2012) 1310–1319.
Viktor Tollemar, Zach J. Collier, Maryam K. Mohammed, Michael J. Lee, Guillermo A. Ameer, Russell R. Reid.“Stem cells, growth factors and scaffolds in craniofacial regenerative medicine.” Genes & Diseases (2015) xx, 1e16.
Maria G. Raucci, Vincenzo Guarino and LiugiAmbrosio. “Biomimetic strategies for bone repair and regeneration.” Journal of functional biomaterials. 2012, 3, 688-705.
Shihori Tanabe. “Role of mesenchymal stem cells in cell life and their signalling.” World journal of stem cells.2014 jan26; 6(1): 24-32.
Chai Y, Maxson RE Jr 2006. “Recent advances in craniofacial morphogenesis.” Dev.
Doble BW, Woodgett JR 2003. “GSK-3: tricks of the trade for a multi-tasking kinase.” J Cell Sci 116: 1175–1186.
Cohen P, Frame S 2001 “The renaissance of GSK3.” Nat Rev Mol Cell Biol 2: 769 –776 Dyn 235: 2353–2375.
Koo SH, Cunningham MC, Arabshahi B, Gruss JS, Grant JH 2001 “The transforming growth factor-beta 3 knock-out mouse: an animal model for cleft palate.” Plast Reconstr Surg 108: 938–948.
Cui X-M, Shiomi N, Chen J, Saito T, Yamamoto T, Ito Y, Bringas P, Chai Y, Shuler CF 2005. “Overexpression of Smad in Tgf-beta3-null mutant mice rescues cleft palate.” Dev Biol 278: 193–202.
Yang LT, Kaartinen V 2007. “Tgfb1 expressed in the Tgfb3 locus partially rescues the cleft palate phenotype of Tgfb3 null mutants.” Dev Biol 312: 384–395.
Juriloff DM, Harris MJ, McMahon AP, Carroll TJ, Lidral AC 2006. “Wnt9b is the mutated gene involved in multifactorial nonsyndromic cleft lip with or without cleft palate in A/WySn mice, as confirmed by a genetic complementation test.” Birth Defects Res A Clin Mol Teratol 76: 574–579.
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
Tel: (001)347-983-5186