The authors recommend periodic evaluation for stage I to II auricular arteriovenous malformation and intervention if there is evolution to stage III. Preoperative embolization and partial or total amputation effectively control auricular and para-auricular arteriovenous malformation. Embolization can be palliative in children or in patients who are not psychologically prepared for amputation. Extensive extra-auricular arteriovenous malformation requires individualized endovascular therapy and resection.

Infantile hemangioma is an endothelial tumor that grows rapidly after birth but slowly regresses during early childhood.

Background-Infantile hemangiomas (IHs) can cause significant morbidity during proliferation, yet there is no FDA-approved treatment. IHs are believed to form from stem cells (HemSCs), which differentiate towards an endothelial cell (HemECs) phenotype. Recently, propranolol has demonstrated effectiveness in the treatment of complicated IHs. We hypothesize that propranolol facilitates IH involution by altering cellular behavior in both HemECs and HemSCs.

OBJECTIVE The aim of our study is to determine the cellular and molecular origin for the pericytes in infantile hemangioma (IH) and their functional role in the formation of pathological blood vessels. METHODS AND RESULTS Here we show that IH-derived stem cells (HemSCs) form pericyte-like cells. With in vitro studies, we demonstrate that HemSC-to-pericyte differentiation depends on direct contact with endothelial cells. JAGGED1 expressed ectopically in fibroblasts was sufficient to induce HemSCs to acquire a pericyte-like phenotype, indicating a critical role for JAGGED1. In vivo, we blocked pericyte differentiation with recombinant JAGGED1, and observed reduced formation of blood vessels, with an evident lack of pericytes. Silencing JAGGED1 in the endothelial cells reduced blood vessel formation and resulted in a paucity of pericytes. CONCLUSIONS Our data show that endothelial JAGGED1 controls HemSC-to-pericyte differentiation in a murine model of IH and suggests that pericytes have a fundamental role in formation of blood vessels in IH.

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The face distinguishes one human being from another. When the face is disfigured because of trauma, tumor removal, congenital anomalies, or chronic diseases, the patient has a strong desire for functional and esthetic restoration. Current practice of facial reconstruction using autologous grafts, synthetic fillers, and prostheses is frequently below the surgeon's and patient's expectations. Facial reconstruction is yet to take advantage of recent advances in seemingly unrelated fields of stem cell biology, chemical engineering, biomaterials, and tissue engineering. "Biosurgery," a new concept that we propose, will incorporate novel principles and strategies of bioactive cues, biopolymers, and/or cells to restore facial defects. Small facial defects can likely be reconstructed by cell homing and without cell transplantation. A critical advantage of cell homing is that agilely recruited endogenous cells have the potential to harness the host's innate capacity for regeneration, thus accelerating the rate of regulatory and commercialization processes for product development. Large facial defects, however, may not be restorable without cell delivery per our understanding at this time. New breakthrough in biosurgery will likely originate from integrated strategies of cell biology, cytokine biology, chemical engineering, biomaterials, and tissue engineering. Regardless of cell homing or cell delivery approaches, biosurgery not only will minimize surgical trauma and repetitive procedures, but also produce long-lasting results. At the same time, caution must be exercised against the development of products that lack scientific basis or dogmatic combination of cells, biomaterials, and biomolecules. Together, scientifically derived biosurgery will undoubtedly develop into new technologies that offer increasingly natural reconstruction and/or augmentation of the face.

We investigated whether Notch signaling plays a role in regulating macrophage responses to inflammation. In a wound healing assay, macrophage recruitment was decreased in Notch1+/− mice, and the wounds were characterized by decreased TNF-α expression. As wound healing progressed, Notch1+/− wounds had increased vascularization and collagen deposition compared with wild-type wounds. In mice with myeloid-specific Notch1 deletion, wounds had decreased macrophage recruitment as well as decreased TNF-α expression, indicating the specific role of Notch1 in the inflammatory response in these cells. In vitro, we found that vascular endothelial growth factor receptor-1 (VEGFR-1) was upregulated in macrophages in response to LPS/IFN-γ and that this upregulation depended on Notch signaling. Furthermore, macrophages from Notch1+/− mice had decreased expression of VEGFR-1 compared with macrophages from wild-type mice, whereas VEGFR-1 expression in Notch4−/− macrophages was normal. Inhibition of Notch signaling decreased induction of the inflammatory cytokines IL-6, IL-12, CXCL10, MCP-1, monokine induced by IFN-γ, and TNF-α in macrophages in response to LPS/IFN-γ. Additionally, macrophages from Notch1+/− mice demonstrated decreased induction of IL-6, IL-12, and TNF-α in response to stimulation compared with wild-type mice. Thus, both pharmacological inhibition of Notch and genetic analysis demonstrate that Notch1 regulates VEGFR-1 and cytokine expression in macrophages. We have also established that Notch1 is important for the inflammatory response during wound healing in mice.

Rarely does the appearance of a child with a repaired bilateral cleft lip compare favorably with that of a child with a repaired unilateral cleft lip. However, there has been a major change in operative strategy during the past decade, and as a result, the typical bilateral cleft nasolabial stigmata are no longer so obvious. The senior author restates the principles for correction of bilateral cleft lip and nasal deformity, and underscores the essential role of preoperative premaxillary positioning. He reviews his method of single-stage closure of the cleft primary palate, including three-dimensional adjustments based on predicted four-dimensional changes. Operative modifications are described for variations of bilateral cleft lip. The authors emphasize the surgeon's obligation for periodic assessment. In a consecutive series of 50 patients with repaired bilateral complete cleft lip/palate, the revision-rate was 33% as compared with 12.5% if the secondary palate is intact. No revisions were necessary for philtral size or columellar length. The authors propose that nasolabial appearance and speech are the priorities in habilitation of the child with bilateral cleft lip/palate rather than the traditional emphasis on maxillary growth.