Andrew Gassman

Molecular mediators of angiogenesis.

Angiogenesis, or the formation of new blood vessels from the preexisting vasculature, is a key component in numerous physiologic and pathologic responses and has broad impact in many medical and surgical specialties. In this review, we discuss the key cellular steps that lead to the neovascularization of tissues and highlight the main molecular mechanisms and mediators in this process. We include discussions on proteolytic enzymes, cell-matrix interactions, and pertinent cell signaling pathways and end with a survey of the mechanisms that lead to the stabilization and maturation of neovasculatures.

Complications of orthognathic surgery.

Complications in orthognathic surgery may stem from occurrences at anyone of many time points during the course of the patients treatment: preoperative judgment and planning, perioperative orthodontic care, or intraoperatively. This article specifically addresses those complications that arise as a result of intraoperative technique. Such complications may broadly be characterized as airway, vascular, neurologic, infectious, skeletal, or aesthetic in nature. For each type, specific complications, their prevention, and their treatment are discussed.

Periosteum-guided prefabrication of vascularized bone of clinical shape and volume.

Background: Large craniofacial skeletal defects require complex reconstruction. Vascularized tissue transfer is the current standard in treatment, but these operations are technically difficult and associated with donor-site morbidity. Guided flap prefabrication offers a technique for endogenously engineering vascularized composite tissues with complex three-dimensional structure. This study evaluates the relationship between implantation time and tissue structure for generating tissues of clinically relevant volume and structure. Methods: Twenty skeletally mature domestic sheep were implanted with poly(methyl methacrylate) chambers designed to mimic the size and shape of the mental protuberance of the mandible. Each chamber was filled with morcellized bone graft and implanted with the open face apposed to the cambium layer of the rib periosteum. Chambers were harvested at 3, 6, 9, 12, and 24 weeks, and the tissue inside the chambers was analyzed for shape conformation to chamber geometry, gross tissue volume, and bone histomorphometric parameters. Results: Histologically, active endochondral, direct, and appositional bone formation was observed. Calcified tissue area and new bone formation increased for each time point up to 12 weeks of implantation. The tissues formed maintained volumetric and geometrical structure consistent with the chamber up to 9 weeks after implantation. Significant decreases in total volume and agreement with chamber geometry were observed at 12 and 24 weeks. Conclusions: Periosteum-guided tissue prefabrication was found to be an effective means of engineering three-dimensional vascularized bone of clinical size and shape. The optimal duration of incubation before significant volume loss occurs is 9 weeks in this large-animal model.

Failed superficial femoral artery intervention for advanced infrainguinal occlusive disease has a significant negative impact on limb salvage.

OBJECTIVE Endovascular treatment of superficial femoral artery (SFA) lesions is a well-established practice. The repercussions of failed SFA interventions are unclear. Our goal was to review the efficacy of SFA stenting and define negative effects of its failure. METHODS A retrospective chart review was conducted from January 2007 to January 2010 that identified 42 limbs in 39 patients that underwent SFA stenting. Follow-up ankle-brachial index and a duplex ultrasound scan was performed at routine intervals. RESULTS Mean patient age was 68 years (range, 43-88 years); there were 22 men (56%) and 17 women (44%). Intervention indication was claudication in 15 patients (36%), rest pain in seven patients (17%), and tissue loss in 19 patients (45%). There were 15 patients (36%) with TransAtlantic Inter-Society Consensus (TASC) A, nine patients (21%) with TASC B, five patients (12%) with TASC C, and 13 patients (31%) with TASC D lesions. The majority of lesions intervened on were the first attempt at revascularization. Three stents (7.7%) occluded within 30 days. One-year primary, primary-assisted, and secondary patency rates were 24%, 44%, and 51%, respectively. Limb salvage was 93% during follow-up. Seventeen interventions failed (40%) at 1 year. Of these, seven patients (41%) developed claudication, seven patients (41%) developed ischemic rest pain, and three patients (18%) were asymptomatic. During follow-up, three patients (7.7%) required bypass and three patients (7.7%) major amputation, one after failed bypass. All limbs requiring bypass or amputation had TASC C/D lesions. Thirty-day and 1-year mortality was 2.6% and 10.3%, respectively. CONCLUSIONS Interventions performed for TASC C/D lesions are more likely to fail and more likely to lead to bypass or amputation. Interventions performed for TASC C/D lesions that fail have a negative impact on limb salvage. This should be considered when performing stenting of advanced SFA lesions.

Characterization of the chemotactic and mitogenic response of SMCs to PDGF-BB and FGF-2 in fibrin hydrogels

The delivery of growth factors to cellularize biocompatible scaffolds like fibrin is a commonly used strategy in tissue engineering. We characterized smooth muscle cells (SMC) proliferation and chemotaxis in response to PDGF-BB and FGF-2, alone and in combination, in 2D culture and in 3D fibrin hydrogels. While both growth factors induced an equipotent mitogenic response in 2D culture, only FGF-2 was significantly mitogenic for SMCs in 3D culture. Only PDGF-BB was significantly chemotactic in a modified Boyden chamber assay. In a 3D assay of matrix invasion, both growth factors induced an invasive response into the fibrin hydrogel in both proliferating and nonproliferating, mitomycin C (MMC) treated cells. The invasive response was less attenuated by the inhibition of proliferation in PDGF-BB stimulated cells compared with FGF-2 stimulated cells. We conclude that SMCs cultured in fibrin hydrogels have a more robust chemotactic response to PDGF-BB compared with FGF-2, and that the response to FGF-2 is more dependent on cell proliferation. Delivery of both growth factors together potentiates the chemotactic, but not mitogenic response to either growth factor alone.

Three-dimensional 10% cyclic strain reduces bovine aortic endothelial cell angiogenic sprout length and augments tubulogenesis in tubular fibrin hydrogels

The development of a functional microvasculature is critical to the long‐term survival of implanted tissue‐engineered constructs. Dynamic culture conditions have been shown to significantly modulate phenotypic characteristics and stimulate proliferation of cells within hydrogel‐based tissue engineered blood vessels. Although prior work has described the effects uniaxial or equibiaxial mechanical stimulation has on endothelial cells, no work has outlined effects of three‐dimensional mechanical stimulation on endothelial cells within tubular vessel analogues. We demonstrate here that 7 days of 10% cyclic volumetric distension has a deleterious effect on the average length and density of angiogenic sprouts derived from pellets of bovine aortic endothelial cells. Although both groups demonstrated lumen formation, the sprouts grown under dynamic culture conditions typically had wider, less‐branching sprout patterns. These results suggest that prolonged mechanical stimulation could represent a cue for angiogenic sprouts to preferentially develop larger lumens over cellular migration and subsequent sprout length. Copyright

Aspirin usage is associated with improved prosthetic infrainguinal bypass graft patency

The American Heart Association recommends that, unless contraindicated, all patients undergoing surgical revascularization for critical limb ischemia should be placed postoperatively on antiplatelet therapy and remain on it indefinitely. The goal of this study was to evaluate if preoperative use of aspirin was associated with improved bypass grafting patency rates and limb salvage. We performed a four-year, retrospective review of one centers experience with open infra-inguinal bypass. We examined the effect pre- and postoperative usage of antiatherosclerotic agents (i.e. aspirin, statin, etc.) have on graft outcomes such as two-year secondary patency, stenosis and limb salvage via univariate Kaplan–Meir survival curve analysis and multiple regression analysis. Our cohort included 165 bypasses in individuals with multiple co-morbidities. The most frequent indication was critical limb ischemia (79%) and most bypasses crossed the knee (63%). Pre- and postoperative aspirin usage was associated with increased two-year secondary prosthetic graft patency over control (preoperative: 78% versus 44%, P < 0.002 and postoperative: 72% versus 50%, P < 0.01). Preoperative aspirin usage was associated with an improvement in the rate of amputation (odds ratio [OR] = 0.44 [95% CI 0.198–0.997]) and stenosis (OR = 0.45 [95% CI 0.217–0.956]). Medications commonly prescribed for atherosclerosis such as aspirin are associated with a significant patency benefit when administered pre- and postoperatively. In a population undergoing infrainguinal bypass with prosthetic graft for predominantly critical limb ischemia, medical optimization should include both pre- and postoperative antiatherosclerotic drug regimens.

Correlation Between Facial Nerve Axonal Load and Age and Its Relevance to Facial Reanimation

Background: Two-stage facial reanimation procedures with a cross-facial nerve graft often have unsatisfactory results in the older patient. Although the cause of result variability is likely multifactorial, some studies suggest that increased donor nerve axonal load improves function of a free muscle transfer after a cross-facial nerve graft. This study attempts to characterize the relationship between age and facial nerve axonal load. Methods: Sixty-three fresh cadaveric heads were dissected to expose the facial nerve. For each hemiface, two facial nerve samples were taken: one proximal as the nerve exits the stylomastoid foramen, and one distal at the buccal branch (at a point 1 cm proximal to the anterior parotid border). Nerve samples were stained and quantified. Correlation analysis was completed using a Pearson correlation coefficient. Results: Thirty-six female and 27 male cadavers were dissected; their average age was 71 years (range, 22 to 97 years). At the proximal (r = −0.26; p < 0.01; n = 104) and distal (r = −0.45; p < 0.0001; n = 114) sampling points, there was a significant negative correlation between age and axonal load. Conclusions: As age increases, the axonal load of the facial nerve decreases at the buccal and zygomatic branches approximately 1 cm proximal to the anterior parotid border. The authors previously suggested this location as significant for cross-facial nerve coaptation. These results propose that decreasing axonal load can be a factor in the unsatisfactory outcomes of cross-facial grafting in the aging population. Moreover, this underscores the importance of recruiting more donor axons in attempting to improve facial reanimation in the older patient.

Remote Ischemic Preconditioning Improves the Viability of Donor Lipoaspirate during Murine Fat Transfer.

Background: Variable results associated with fat grafting have been attributed to local trauma, inconsistencies in transfer, and ischemia before the development of recipient circulation. Remote ischemic preconditioning is an inexpensive noninvasive technique that has been used in animal models and multicenter clinical trials to protect organ systems. In this work, the authors describe a novel animal model for analyzing the efficacy of fat grafting, and investigate the effect of remote ischemic preconditioning on volume retention. Methods: Subcutaneous adipose tissue samples from green fluorescent protein/luciferase-expressing FVB mice were obtained with or without pretreatment with a temporary hind-limb tourniquet. The samples were injected into the dorsal skin folds of wild-type FVB mice. The viability of the transferred tissue was examined over a 28-day period with quantitative bioluminescence after luciferin injection. Transferred tissue was also explanted for histologic analysis. Results: The remote ischemic preconditioning group had significantly increased bioluminescence at days 0, 1, and 28. Histologic analysis at day 28 confirmed the presence of vascularized adipose in both groups. However, significant amounts of interstitial fibrosis were found in the control group, whereas substantially less was found in the remote ischemic preconditioning group. The remote ischemic preconditioning group retained a substantially greater amount of green fluorescent protein, suggesting increased survival of donor adipocytes. Conclusions: In this work, the authors describe a novel animal model for quantitative evaluation of fat grafting using in vivo bioluminescence of adipocytes from luciferase-expressing mice. The authors also demonstrate that remote ischemic preconditioning increases the viability of fat transfer and decreases interstitial fibrosis.

Facial Danger Zones: Techniques to Maximize Safety during Soft-Tissue Filler Injections.

Summary: Given the short recovery and immediate results, facial fillers have become a popular alternative to surgical rejuvenation of the face. Reported complications arising from facial filler injections include erythema, tissue loss, blindness, stroke, and even death. In this article, the authors describe their anatomically based techniques to minimize risk and maximize safety when injecting in the facial danger zones, including the glabella/brow, temporal region, perioral region, nasolabial fold, nose, and infraorbital region. Complications generally arise secondary to vasculature injury and/or cannulation with filler. The authors have outlined their preferred injection techniques in the facial danger zones with respect to the pertinent anatomy in an attempt to minimize risk and maximize results. Most importantly, the practitioner should be able to recognize complications and address them immediately.