Correction of alveolar cleft with calcium-based bone substitutes.

In the article entitled ‘‘Correction of alveolar cleft with calciumbased bone substitute,’’ Lazarou et al report the use of Stimulan (Biocomposites, Staffordshire, UK) as a substitute to autologous bone in primary alveolar cleft bone grafting. In their study, 10 infants with complete unilateral cleft lip and palate underwent gingivoperiosteoplasty (GPP) between 9 and 12 months of age (the cleft lip had been previously repaired in a separate procedure). During the GPP, after the closure of the nasal and oral mucosa, calcium sulfate powder and/or pellets were stacked in the alveolar cavity, and then the GPP pocket was closed. No fistula or infection occurred. Mean follow-up was 5.1 years. In each patient, deciduous tooth eruption occurred in the cleft area. Panorex and occlusal radiography, performed at the age of 4 years, documented bone formation. None of the patients required secondary bone grafting at the end of the study period. The authors conclude that primary grafting of Stimulan allows tooth eruption and that this ‘‘off-theshelf’’ material presents a significant advantage over other biomaterials and autologous tissue in the correction of alveolar clefts. Lazarou et al are rightly addressing a complex problem in cleft surgery, and they should be commended for their effort. Around the world, alveolar cleft are treated with a wide array of techniques, and despite the lack of preclinical data, some centers provide off-label, noncontrolled treatment for patients with congenital alveolar clefts. Although the initial data from these human reports are exciting, they are largely uncontrolled, and the patients are not randomized. Without adequate study design and appropriate controls, the skeptic is left wondering whether a new approach is any better than an older one. Currently, the 3 main approaches to alveolar cleft are (1) secondary alveolar bone grafting during mixed dentition (aged between 7 and 9 y), (2) presurgical orthopedics with primary GPP at the time of primary lip repair, and (3) early alveolar bone grafting in the first year of life with autogenous bone graft. Secondary autologous bone grafting during mixed dentition has a 68% to 96% rate of success and is the most common technique around the world. Preoperative orthopedic molding is designed to reduce the alveolar gap so that a primary gingivoperiosteoplasty is possible. With optimal preoperative molding and primary GPP, 41% to 73% of patients have sufficient alveolar bone formation for eruption of the adult teeth or implant placement. To achieve optimal results, this approach requires an experienced team, including a craniofacial orthodontist to closely approximate the alveolar segments (G1 mm) with a custommade appliance before the GPP and a skilled cleft surgeon to operate in a small space to elevate the tissues only at the edge of the cleft margin and avoid damage to the tooth buds. Bone grafting is not necessary in this procedure because the periosteum serves as an osteogenic substrate, but patients for whom a primary GPP is unsuccessful will require secondary bone grafting at age 7 to 9 years. Early alveolar bone grafting without presurgical orthodontics leads to bone formation if the alveolar cleft is narrow; however, there tends to be a high incidence of maxillary hypoplasia because of the extensive subperiosteal dissection necessary to close the alveolar cleft. Furthermore, if the alveolar cleft is wide, the central portion of the graft is unlikely to be revascularized. Although each technique may produce satisfactory results in experienced hands, none has indisputably been shown to be superior. For many surgeons today, bone grafting of the alveolar cleft remains the standard of care. Although many surgeons will argue that cancellous iliac bone graft can be harvested in a 7-year-old in less than 15 minutes through a 1-cm incision with minimal bleeding, minimal postoperative pain, and no functional sequelae, such a harvest is more challenging in an infant. Corticocancellous bone harvested from the ribs or the calvaria is less likely to be revascularized than cancellous bone harvested from the ilium or the tibial crest. Moreover, harvesting bone from the lower extremity weakens the anterior cortical of the tibia increasing the risk of postoperative tibial fractures. In sum, avoiding bone-graft donor site morbidity at any age is a goal in alveolar cleft surgery. In their study, Lazarou et al used an acellular scaffold marketed under the name of Stimulan. Stimulan is a medicaland implantgrade calcium sulfate (CaSO4), a compound better known as plaster of Paris, created by heating gypsum to 150-C (the large gypsum deposit at Montmartre in Paris is the source of the name). Plaster of Paris has been widely used in orthopedic surgery since the mid 19th century to build casts to immobilize fractures. In 1959, Peltier used it to fill large bone defects. Biocomposites (Staffordshire, UK) started to offer a decade ago high-quality synthetic implantable CaSO4 for orthopedic indications (fractures, filling of aneurismal bone cyst sites, filling of benign giant cell tumor sites, and osteomyelitis), obtaining European Community and US Food and Drug Administration approvals in the above-mentioned indications. In this alveolar cleft study, Stimulan is used as an off-label device. Synthetic high-purity calcium sulfate acts as an acellular scaffold, to be colonized by osteoprogenitor cells and grow new bone, in a manner similar to the mineral-based osteoconductive calcium phosphate ceramics scaffold that we and others are currently investigating in the laboratory. The chemical anisotropic materials most often used to construct polycrystalline ceramics are hydroxyapatite (HA) and tricalcium phosphate (TCP). These ceramics have been targeted because they have the native composition of bone, mechanical features similar to bone, controlled absorption, and biologically active properties that are believed to facilitate osteogenic differentiation of mesenchymal stem cells. When transplanted as acellular scaffolds, their chemical properties promote recruitment of osteoprogenitor cells, vascular invasion, and bone formation. Interestingly, in their study, Lazarou et al achieved satisfactory bone formation DISCUSSION