Michael H. Carstens

Repair of alveolar clefts with recombinant human bone morphogenetic protein (rhBMP-2) in patients with clefts.

This article demonstrates the feasibility of using recombinant human bone morphogenetic protein (rhBMP-2) as a substitute for autogenous iliac crest bone for repair of congenital facial clefts in humans. In this series, 50 cleft sites were repaired in 43 patients using rhBMP-2 without the use of autogenous graft tissue. Successful osseous union was achieved in 49 of the 50 sites. In one patient, the graft failed to consolidate. Severe clefts were managed by combining distraction osteogenesis and rhBMP-2. Eliminating the need to harvest autogenous iliac crest bone resulted in substantial decrease in morbidity. The constructed alveolus performed clinically as normal bone and responded to natural tooth eruption and orthodontic movement. Histology of the tissue constructed showed normal, vital bone. Although additional investigation is warranted to determine the optimum protocol for the use of this material in alveolar cleft repair, the technique should be considered as a viable treatment option in cases in which avoiding iliac crest harvesting is desirable.

Reconstruction of #7 facial cleft with distraction-assisted in situ osteogenesis (DISO): role of recombinant human bone morphogenetic protein-2 with Helistat-activated collagen implant.

A case involving concomitant presentation of a #7 lateral facial cleft with a complete cleft of the ipsilateral lip, alveolus, and palate is presented. The mandibular defect was Pruzansky III with a foreshortened body, absent ramus and absent masseter. Taking advantage of developmental field theory, reconstruction of the osseous defect was undertaken using the autogenous periosteum as a source of mesenchymal stem cells. Expansion of the periosteum was followed by implantation of Helistat (Integra Life Sciences, Plainsboro, NJ) collagen sponge saturated with recombinant human bone morphogenetic protein-2. Stimulation of this distraction-induced envelope by rhBMP-2 resulted in abundant production of bicortical membranous bone in situ within 12 weeks. The neoramus was subsequently suspended from the cranial base, and a temporalis muscle transfer was used to provide motor control of the jaw. Synthesis of bone in this manner is termed DISO (distraction-assisted in situ osteogenesis). The biologic rationale and clinical implications of DISO are discussed.

Development of the Facial Midline

“Intellectual excellence lies in having faith in the observation of apparently nontranscendental and unimportant facts. To observe an anatomic element calmly, with an open, analytical spirit, and with spiritual freedom, can lead to an explosive vortex of new knowledge.” –Miguel Orticochea, M.D. 1Traditional descriptive embryology based upon the interaction of frontonasal, lateral nasal, and medial nasal prominences is incapable of explaining the three-dimensional development of the facial midline. The internal structure of the nose and that of the oronasal midline can best be explained by the presence of paired A fields originating from the prechordal mesendoderm, associated with the nasal and optic placodes, supplied by the internal carotid artery, and sharing a common genetic coding with the prosomeres of the forebrain. Mesial drift of these fields leads to fusion of their medial walls; this in turn provides bilateral functional matrics within which form the orbits ethmoids, lacrimals, turbinates, premaxillae, vomerine bones, and the cartilages of the nose. This two-part paper reports six lines of evidence supporting the field theory model of facial development: (1) An apparent watershed exists in the midline of the base between the territories of the internal and external carotid systems. Isolation of the ICA in injected fetal specimens confirmed that the demarcation was distinct and restricted to the embryonic nasal capsule. (2) Field theory explains the developmental anatomy of the contents of the nasal capsule. (3) The neuromeric model of CNS development provides a genetic basis for the anatomy and behavior of fields. (4) Mutants for the Dlx5 gene demonstrate A field deletion patterns. These experiments relate the nasal placode to the structures of the A fields. (5) Separate regions of the original nasal placodes give rise to neurons, which are dedicated to separate sensory and endocrine systems. The A fields constitute the pathways by which these neurons reach the brain. (6) Non–cleft lip-related cleft palate, holoprosencephaly, and the Kallmann syndrome are clinical models that demonstrate the effects of anatomic disturbances within the A fields.

In Situ Osteogenesis of Hemimandible With rhbmp-2 in a 9-year-old Boy: Osteoinduction Via Stem Cell Concentration

J uvenile active ossifying fibroma (JAOF) is a benign fibro-osseous lesion with a tendency to occur in children and adolescents. Its clinical behavior is notable for locally aggressive growth within the craniofacial bones and a significant recurrence rate, varying between 30% and 58%. Although this is a rare lesion, it can result in significant facial distortion in a young patient. Controversy exists regarding the treatment of JAOF. There are proponents for both enucleation and complete resection. When a tumor reaches a size that mandates resection of the involved bone, the focus should be on achieving the best functional and aesthetic reconstruction for the child. The authors present a case of recurrent, locally aggressive tumor requiring hemimandibulectomy and a new technique for mandible reconstruction involving in situ osteogenesis with recombinant bone morphogenetic protein (rhBMP-2).

The spectrum of minimal clefting: process-oriented cleft management in the presence of an intact alveolus.

The minimal cleft lip provides a model for study of the clefting process. Nasolabial embryogenesis can be best understood using the concept of embryonic fields in which midline structures (columella, philtrum, premaxilla, septum, vomer, and ethmoids) develop with paired, fused A fields. Anatomic features of the minimal cleft lip suggest that the actual clefting site is located at the interface between the A and B fields within the lateral piriform wall. Study of the progression of clefting, using this model, places the timing of the clefting event to Carnegie stage 14. The degree to which this initial event affects subsequent fusion of the lateral and medial nasal processes (D and C fields) determines the final morphology of the cleft. Using this model, a rational basis is presented for the surgical management of minimal clefting in its varying manifestations.

Sequential cleft management with the sliding sulcus technique and alveolar extension palatoplasty.

Conventional methods of cleft lip repair deprive the anterior (buccolingual) alveolar mucoperiosteum of blood supply from the facial-internal maxillary arcade. Six months later, at palatoplasty, lingual incisions permanently isolate the lingual mucoperiosteum from its blood supply--the greater palatine artery. The osteogenic alveolar mucoperiosteum is thus converted from a richly supplied boundary zone between the two angiosomes into an isolated tissue dependent on osseus backflow. Cleft-sided growth disturbance is considered from this perspective. Subperiosteal techniques that preserve the blood supply to this tissue are considered in a sequential plan of cleft management.

Neuroembryology and functional anatomy of craniofacial clefts

The master plan of all vertebrate embryos is based on neuroanatomy. The embryo can be anatomically divided into discrete units called neuromeres so that each carries unique genetic traits. Embryonic neural crest cells arising from each neuromere induce development of nerves and concomitant arteries and support the development of specific craniofacial tissues or developmental fields. Fields are assembled upon each other in a programmed spatiotemporal order. Abnormalities in one field can affect the shape and position of developing adjacent fields. Craniofacial clefts represent states of excess or deficiency within and between specific developmental fields. The neuromeric organization of the embryo is the common denominator for understanding normal anatomy and pathology of the head and neck. Tessiers observational cleft classification system can be redefined using neuroanatomic embryology. Reassessment of Tessiers empiric observations demonstrates a more rational rearrangement of cleft zones, particularly near the midline. Neuromeric theory is also a means to understand and define other common craniofacial problems. Cleft palate, encephaloceles, craniosynostosis and cranial base defects may be analyzed in the same way.

Mandibular distraction using bone morphogenic protein and rapid distraction in neonates with Pierre Robin syndrome.

Introduction: Mandibular distraction is recognized as a treatment of respiratory distress in neonates with microretrognathia as seen in the Pierre Robin syndrome. However, mandibular distraction is a complex and lengthy treatment involving 2 to 4 weeks of distraction and another 4 to 12 weeks for bone consolidation. This study was performed to establish the safety and effectiveness of rapid protocol distraction osteogenesis with recombinant human bone morphogenetic protein 2 (rhBMP-2) in neonates with the Pierre Robin syndrome. Methods: A retrospective review of all patients treated in our department between February 2003 and February 2008 was performed. Three patients with the Pierre Robin syndrome who underwent distraction osteogenesis with rhBMP-2 were identified. Inpatient and outpatient charts were reviewed for time to completion of distraction, age at distraction, need for tracheostomy, and complications of the mandibular distraction. Results: Three patients (6 hemimandibles) with Pierre Robin syndrome underwent rapid protocol distraction with rhBMP-2. Mean age at initial distraction was 17.3 days. Mean time from device placement to removal was 89.3 days. The complication rate was 16%, with 1 case of nonunion that required subsequent operative intervention. No patient required tracheostomy. Conclusions: Rapid protocol distraction with rhBMP-2 allows distraction of the hypoplastic mandible to class III occlusion during the initial operation and avoids the latency and distraction phases of standard mandibular distraction. This case series demonstrates the safety and effectiveness of rapid distraction in neonates with Pierre Robin syndrome. Larger studies and long-term follow-up are necessary; however, this study suggests that rapid protocol distraction with rhBMP-2 is effective in neonates with Pierre Robin syndrome.

Non-reconstructable peripheral vascular disease of the lower extremity in ten patients treated with adipose-derived stromal vascular fraction cells

We present a series of ten patients with non-reconstructable peripheral vascular disease (PVD), secondary to arteriosclerosis (AS) and/or diabetes mellitus (DM), treated with local injection of non-expanded autologous, adipose-derived stromal vascular fraction (SVF) cells for the purposes of enhancing neovascularization and chronic wound healing. Adipose tissue was surgically harvested and processed to yield the heterogeneous SVF cells for immediate point-of-care injection. The gastrocnemius muscles and ulcers or wounds where present were locally injected with the resulting SVF. Response to treatment was evaluated both clinically based on pain-free ambulation, wound healing capacity over time and ankle/brachial index (ABI) measurements, and by imaging using MRI-based angiography. All patients exhibited clinical improvement (reduction in rest pain and claudication and improvements in ABI), with imaging signs of neovascularization in the majority (5 of 6) of patients in whom the evaluation was feasible. Similarly, 5 of 6 chronic wounds healed without further surgical intervention. This series highlights the utility of non-expanded adipose-derived heterogeneous SVF cell population processed at the point-of-care, to treat patients with end-stage PVD as an alternative to palliation or amputation.

Functional matrix cleft repair: a common strategy for unilateral and bilateral clefts.

&NA; At first glance, the morphologies of unilateral and bilateral clefts appear quite distinct. So much so, that many authors describe them as separate entities altogether. This has given rise to disparate surgical strategies. This paper presents a unifying theory of pathogenesis and treatment.