The precise mechanisms of normal and abnormal scar formation have long remained a mystery despite the extensive literature regarding wound healing. Only recently have researchers begun to delineate ...the complex biochemical signaling pathways that regulate these processes. This article reviews basic wound healing, while focusing on medicine's latest understanding of the development and treatment of keloids and hypertrophic scars.
The importance of the transforming growth factor-beta signaling pathways and the related downstream effector molecules has proven to offer a new detailed view of scar biology. Regulation of scar metabolism with regards to collagen and wound matrix degradation is likewise showing promise in generating alternate therapies to treat abnormal scars.
Understanding the exact process of normal and abnormal scar formation will help define better ways to successfully manage and potentially prevent abnormal healing like hypertrophic scars and keloids.
The authors examined the efficacy of a novel technique for oronasal fistula repair using acellular dermal matrix grafts. In part I, an animal model was used to demonstrate proof-of-concept; in part ...II, the method was applied to oronasal fistula repair in the clinical setting.
In part I, oronasal fistulas were created in Yorkshire piglets (n = 6) and allowed to mature for 2 weeks. In three animals, acellular dermal grafts were interposed between the oral and nasal mucosa traversing the palatal fistulas. Mucosal edges were not closed. Three weeks postoperatively, the palates were examined histologically. The fistulas of control piglets (n = 3) remained unrepaired and were examined 5 weeks after their creation. In part II, acellular dermal grafts were interposed between the oral and nasal mucosa in nine consecutive patients undergoing oronasal fistula repair. Complete closure of the oral and nasal mucosa was achieved in two patients. In the remainder, nasal closure was affected by interposition of the dermal matrices beneath a complete oral mucosal closure.
All animals that underwent fistula repair demonstrated successful healing with revascularization, complete reepithelialization, and cellular infiltration into the grafts. All control fistulas remained patent. Successful fistula closure was observed in all patients. In two patients, early oral mucosal dehiscence and exposure of the dermal graft was followed by complete healing.
This study demonstrates successful closure of palatal fistulas in an animal model and in cleft palate patients using interposition grafts of acellular dermis. This novel method offers promise as a simple and effective technique for tension-free closure of oronasal fistulas.
Abstract Background Subdiaphragmatic aortic diseases in children are rare and form a heterogeneous group. The pediatric patient presents unique challenges because of their size, concerns about proper ...timing and conduit for repair, and anticipating expected growth. Methods We performed a retrospective review of operations involving the abdominal aorta and called branches in children between January 2003 and April 2007, focusing on the details of preoperative evaluation, operative technique, and outcomes. The pertinent literature is reviewed. Results Twenty-two children (age, 2 days to 17 years) were included. Mean follow-up was 28 months. Aneurysms were seen in 5 children; the remainder had stenotic disease. Aneurysms were typically asymptomatic and diagnosed incidentally, whereas stenotic lesions most commonly presented with hypertension (HTN). Fourteen complex vascular repairs were performed. All of the children with aneurysms underwent prompt surgery. The children with stenoses had operations for poorly controlled HTN, claudication, and/or mesenteric ischemia. Most patients with stenotic disease were treated medically for HTN and were followed closely while awaiting optimal size and availability of autogenous conduit for reconstruction. Cryopreserved allograft was used in 3 of the aneurysm operations. Dacron grafts were used to repair 5 aortic stenotic lesions. Renal and mesenteric revascularizations were performed with saphenous vein grafts. Pediatric, general, and transplant surgeons and nephrologic and cardiologic teams were integral to evaluation and management. No major operative complications occurred. Conclusion Proper management of pediatric aortic vascular disease requires a multidisciplinary approach. It is best to use autologous grafts whenever possible. Children with stenotic disease should be treated medically for hypertension until they are large enough for an autologous graft reconstruction. Children with aneurysmal disease are at risk for embolism and thrombosis and therefore usually treated immediately using artificial graft material, if necessary.
The higher prevalence of metopic and sagittal suture synostosis in male infants suggests a role for androgens in early craniofacial development. These experiments characterize the influence of ...androgen stimulation on growth and differentiation of fetal dural and calvarial bone cells and on cranial suture fusion.
Primary murine fetal (E18) dural cells and calvarial osteoblasts were isolated and cultured. Cells were treated for 48 hours with 5alpha-dihydrotestosterone (0 to 1000 nM). Cell proliferation was examined by nonradioactive proliferation assay; mRNA expression of alkaline phosphatase, transforming growth factor (TGF)-beta1, and the bone matrix proteins osteopontin, osteocalcin, and type 1 collagen was determined by reverse-transcriptase polymerase chain reaction. In separate experiments, intact fetal calvariae were grown in tissue culture with 10 nM 5alpha-dihydrotestosterone for 7 and 14 days and then examined histologically.
Androgen stimulation at 5 nM increased proliferation of fetal dural cells by 46.0 percent and of fetal calvarial osteoblasts by 20.5 percent. Dural expression of osteopontin, osteocalcin, and type 1 collagen was enhanced by 5alpha-dihydrotestosterone, as was that of TGF-beta1 and alkaline phosphatase. Androgen stimulation increased calvarial osteoblast expression of alkaline phosphatase and TGF-beta1 but induced little change in expression of osteocalcin, osteopontin, and type 1 collagen. In tissue culture, 5alpha-dihydrotestosterone stimulated osteoid formation and fusion of sagittal sutures.
Androgen stimulation of dural cells and osteoblasts isolated from fetal calvaria promotes cell proliferation and osteoblastic differentiation and can induce cranial suture fusion. These results suggest that sex steroid hormone signaling may stimulate sutural osteogenesis by means of osteodifferentiation of dural cells, thus explaining the male prevalence of nonsyndromic craniosynostosis.
Calcium phosphate cements have been recently introduced for use in craniofacial reconstruction. In the clinical setting, however, pulsations of the underlying brain and dura may interfere with the ...crystallization of these cements, thereby rendering their use in cranioplasty problematic. To circumvent such problems, many clinicians have interposed synthetic resorbable plates or mesh between the dura and the cement. At the present time, however, little is known about the influence of such materials or their breakdown products on the fate of calcium phosphate cements. The specific aim of this project was to evaluate the biocompatibility, osteoconductivity, and remodeling capacity of a calcium phosphate cement after implantation into experimental calvarial defects when combined with a resorbable mesh underlay. Four 10-mm diameter full-thickness calvarial defects (two frontal, two parietal) were created in each of six 3-week-old Yorkshire pigs. The defects were treated as follows: 1) empty control, 2) macroporous polylactic acid (70/30 L/DL polylactic acid PLA) mesh, 3) Norian CRS calcium phosphate cement, and 4) Norian CRS over PLA mesh underlay. Animals were divided into two groups. Half of the animals were killed 30 days after surgery, and half were killed 180 days after surgery, and the graft recipient sites were examined histologically. At 30 days, minimal bone ingrowth was observed in untreated calvarial defects or in those that were treated with PLA plates alone. Defects treated with the cement alone demonstrated a modest amount of new woven bone deposition, primarily at the periphery of the implants. Defects treated with calcium phosphate cement over PLA mesh underlays were characterized by remodeling and woven bone deposition at 30 days, with complete or near-complete osseous bridging of the ectocranial implant surfaces. Progressive bone ingrowth was noted in all defects at 180 days, with near-complete replacement of all Norian CRS implants by host bone. The PLA mesh remained incompletely resorbed at 180 days. No inflammatory response to the implants was observed at either time point. Calcium phosphate cement may be safely used for craniofacial reconstruction in the presence of PLA implants without compromise to its biocompatibility, osteoconductivity, or remodeling capacity.
Male predominance in metopic and sagittal craniosynostosis and in nonsynostotic plagiocephaly suggests a role for circulating androgens in early craniofacial development. Androgens have been ...documented to play an important role in postnatal skeletal growth, and the androgen receptor has been recently demonstrated in human and rat osteoblast-like cell lines and in human long bones. The purpose of this study was to describe the expression of androgen receptor in the fetal craniofacial skeleton. The heads of E18 fetal CD-1 male and female mice were fixed in 10% formalin, decalcified, and embedded in paraffin. Four- to 6-mum coronal and sagittal sections were stained with a monoclonal antibody specific to androgen receptor, which was detected by an avidinbiotin conjugate and peroxidase system. The sections were then examined for androgen receptor expression patterns. Strong androgen receptor immunoreactivity was observed in the dura mater of developing fetuses. Androgen receptor expression was also noted in cells lining the osteogenic fronts and in calvarial osteoblasts. Similar androgen receptor expression patterns were found in male and female mice. Androgen receptor is abundantly expressed in fetal dura mater and calvarial bone. This study confirms the presence of androgen receptor in the murine fetal craniofacial skeleton, suggesting a potential role for the anabolic effects of androgens in the developing craniofacial skeleton.
