The need to provide rigid bony fixation in the surgical treatment of craniofacial deformities has inspired an on-going evolution of surgical innovations and implants. Because of the young age of many treated craniosynostosis patients and the unique pattern of cranial vault growth, the extensive implantation of metal devices is potentially problematic. The use of resorbable plate and screw devices offers all of the benefits of rigid fixation without many of their potential risks. Since the introduction of resorbable plate and screw devices in 1996, tens of thousands of craniofacial patients have received implants, but long-term results from a large series have yet to be reported. A combined prospective and retrospective analysis was done on 1883 craniosynostosis patients under 2 years of age treated by 12 surgeons from seven different geographic locations over a 5-year period who used the same type of resorbable bone fixation devices (poly-L-lacticpolyglycolic copolymer). Specifically, the incidence of postoperative infection, fixation device failure, occurrence of delayed foreign-body reactions, and the need for reoperation resulting from device-related problems were determined. Technical difficulties and trends in device use were also noted. From this series, significant infectious complications occurred in 0.2 percent, device instability primarily resulting from postoperative trauma occurred in 0.3 percent, and self-limiting local foreign-body reactions occurred in 0.7 percent of the treated patients. The overall reoperation rate attributable to identifiable device-related problems was 0.3 percent. Improved bony stability was gained by using the longest plate geometries/configurations possible and bone grafting any significant gaps across plated areas that were structurally important. The specific types of plates and screws used evolved over the study period from simple plates, meshes, and threaded screws to application-specific plates and threadless push screws whose use varied among the involved surgeons. This report documents the safety and long-term value of the use of resorbable (LactoSorb) plate and screw fixation in pediatric craniofacial surgery in the infant and young child. Device-related complications requiring reoperation occurred in less than 0.5 percent of the implanted patients, which is less frequent than is reported for metallic bone fixation. Resorbable bone fixation for the rapidly growing cranial vault has fewer potential complications than the traditional use of metal plates, screws, and wires.

Stem cell fate has been linked to the mechanical properties of their underlying substrate, affecting mechanoreceptors and ultimately leading to downstream biological response. Studies have used polymers to mimic the stiffness of extracellular matrix as well as of individual tissues and shown mesenchymal stem cells (MSCs) could be directed along specific lineages. In this study, we examined the role of stiffness in MSC differentiation to two closely related cell phenotypes: osteoblast and chondrocyte. We prepared four methyl acrylate/methyl methacrylate (MA/MMA) polymer surfaces with elastic moduli ranging from 0.1 MPa to 310 MPa by altering monomer concentration. MSCs were cultured in media without exogenous growth factors and their biological responses were compared to committed chondrocytes and osteoblasts. Both chondrogenic and osteogenic markers were elevated when MSCs were grown on substrates with stiffness <10 MPa. Like chondrocytes, MSCs on lower stiffness substrates showed elevated expression of ACAN, SOX9, and COL2 and proteoglycan content; COMP was elevated in MSCs but reduced in chondrocytes. Substrate stiffness altered levels of RUNX2 mRNA, alkaline phosphatase specific activity, osteocalcin, and osteoprotegerin in osteoblasts, decreasing levels on the least stiff substrate. Expression of integrin subunits α1, α2, α5, αv, β1, and β3 changed in a stiffness- and cell type-dependent manner. Silencing of integrin subunit beta 1 (ITGB1) in MSCs abolished both osteoblastic and chondrogenic differentiation in response to substrate stiffness. Our results suggest that substrate stiffness is an important mediator of osteoblastic and chondrogenic differentiation, and integrin β1 plays a pivotal role in this process.

Hemangioma of infancy is the most common neoplasm of childhood. While hemangiomas are classic examples of angiogenesis, the angiogenic factors responsible for hemangiomas are not fully understood. Previously, we demonstrated that malignant endothelial tumors arise in the setting of autocrine loops involving vascular endothelial growth factor (VEGF) and its major mitogenic receptor vascular endothelial growth factor receptor 2. Hemangiomas of infancy differ from malignant endothelial tumors in that they usually regress, or can be induced to regress by pharmacologic means, suggesting that angiogenesis in hemangiomas differs fundamentally from that of malignant endothelial tumors. Here, we demonstrate constitutive activation of the endothelial tie-2 receptor in human hemangioma of infancy and, using a murine model of hemangioma, bEnd.3 cells; we show that bEnd.3 hemangiomas produce both angiopoietin-2 (ang-2) and its receptor, tie-2, in vivo. We also demonstrate that inhibition of tie-2 signaling with a soluble tie-2 receptor decreases bEnd.3 hemangioma growth in vivo. The efficacy of tie-2 blockade suggests that either tie-2 activation or ang-2 may be required for in vivo growth. To address this issue, we used tie-2-deficient bEnd.3 hemangioma cells, which, surprisingly, were fully proficient in in vivo growth. Previous studies from our laboratory and others have implicated reactive oxygen-generating nox enzymes in the angiogenic switch, so we examined the effect of nox inhibitors on ang-2 production in vitro and on bEnd.3 tumor growth in vivo. We then inhibited ang-2 production pharmacologically using novel inhibitors of nox enzymes and found that this treatment nearly abolished bEnd.3 hemangioma growth in vivo. Signal-transduction blockade targeting ang-2 production may be useful in the treatment of human hemangiomas in vivo.

No abstract

Dog bite injuries remain a common form of pediatric trauma. This single-institution study of 1616 consecutive dog bite injuries over 4 years revealed a much higher prevalence of dog bites as compared with other similar centers. Though inpatient admission was rare (9.8%), 58% of all patients required laceration repair, primarily in the emergency department. Infants were more than 4 times as likely to be bitten by the family dog and more than 6 times as likely to be bitten in the head/neck region. Children ≤5 years old were 62% more likely to require repair; and 5.5% of all patients required an operation. Pit bull bites were implicated in half of all surgeries performed and over 2.5 times as likely to bite in multiple anatomic locations as compared to other breeds. The relatively high regional prevalence and younger age of injured patients as compared with other centers is a topic of further study but should draw attention to interventions that can minimize child risk.

The role of the tensor fasciae latae as autogenous tissue in reconstruction of abdominal wall defects is well established. The use of various forms of the tensor fasciae latae (free graft versus pedicled flap versus free flap) is determined by the characteristics of the defect. A review of abdominal wall reconstructions using tensor fasciae latae was completed to determine efficacy and establish guidelines for its use. Abdominal wall reconstructions from 1991 to 1994 using tensor fasciae latae were reviewed. Demographics, wound characteristics, and complications were evaluated. Twenty-seven patients with a mean follow-up of 23.6 months underwent abdominal wall reconstruction with the tensor fasciae latae: free grafts, 12; pedicled flaps, 9; and free flaps, 6. An average defect size of 14.4 x 13.1 cm was seen. Fourteen (52 percent) of the reconstructions were completed in contaminated or infected wounds. One recurrent enteric fistula was seen. Twelve (44 percent) of the patients had flap complications of which 50 percent involved partial flap necrosis. Donor site complications were seen in five patients (18 percent) and included a hematoma, seroma, and two cases of skin graft dehiscence along the edge of the wound. Tensor fasciae latae free grafts are an option for repair of abdominal hernias if abdominal soft tissue is adequate. Pedicled flaps may be used for defects of soft tissue and fascia but are limited by the arc of rotation and size of the defect. Tensor fasciae latae free flaps are versatile in orientation and may be used for supraumbilical defects. Tip necrosis is significant in both types of vascularized flaps.

A subgroup of mastectomy patients receives adjuvant radiation therapy after autogenous breast reconstruction for locoregional control of cancer. The effects of radiation therapy on pedicled transverse rectus abdominis musculocutaneous (TRAM) flaps were determined to evaluate complication rates and aesthetic results. Nineteen patients from 1981 to 1994 receiving radiation therapy after a pedicled TRAM flap reconstruction were compared with 108 patients who received radiation prior to reconstruction and 572 patients who underwent breast reconstruction without radiation. Retrospective reviews of patient charts were completed. Adjuvant radiation therapy was given for chest-wall recurrence in 13 of 19 patients. With a mean follow-up of 47.6 months from the time of reconstruction, 10 patients (52.6 percent) demonstrated postradiation changes in the TRAM flap reconstruction, and 6 required surgical intervention (31.6 percent). Overall complication rates were increased but were not found to be statistically significant between the radiated TRAM flap group and patients with preoperative radiation followed by TRAM flap reconstruction (31 versus 25 percent). Fibrosis was not found in patients with pre-TRAM flap radiation or in patients without radiation but was seen in 31.6 percent of patients who received radiation after the reconstruction. Fat necrosis was not significantly increased between the two groups of radiated patients. The complication rate does not change whether a patient receives radiation before or after her reconstruction; only the nature of the complication changes (fat necrosis to fibrosis).

The management of velopharyngeal insufficiency using sphincter pharyngoplasty in children with velocardiofacial syndrome is safe and effective. The higher need for surgical revision in velocardiofacial syndrome patients is most likely attributable to a greater degree of preoperative nasalance and a slightly later age of presentation. This should provide insight into various technique modifications in an attempt to minimize pharyngoplasty revision.