Christopher C Chang

American Society of Ophthalmic Plastic and Reconstructive Surgery, New York City, New York, United States

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Publications (12)48.88 Total impact

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    ABSTRACT: Coronoid process hypertrophy can be associated with a variety of congenital or acquired anomalies. There is, however, no consensus on a quantitative or objective measure to define coronoid hypertrophy. Here, the authors describe a novel analytical technique using three-dimensional computed tomographic data to accurately and reproducibly assess coronoid size and diagnose coronoid:condyle disproportion. A total of 24 patients were analyzed using three-dimensional medial axis analysis, eight with of unilateral coronoid hypertrophy, four with of bilateral coronoid hypertrophy, and 12 age-matched normal control patients. Measurement of normal subjects (n = 12) demonstrated a coronoid:condyle volumetric ratio less than or equal to 0.5. Analysis of patients with coronoid hypertrophy demonstrated that a coronoid:condyle volumetric ratio greater than or equal to 1.0 was consistent with marked coronoid:condylar disproportion and a ratio between 0.5 and 1.0 was indicative of modest disproportion. Surface area ratios comparing coronoid with condyle were also elevated (ratio, ≥0.5) in patients with coronoid hypertrophy. Quantitative assessment of coronoid size using three-dimensional volume and surface area analysis of computed tomographic data may be helpful to the clinician in diagnosing coronoid hypertrophy and in guiding treatment. It may also serve a role in monitoring the temporal evolution of coronoid hypertrophy in early cases that have not yet resulted in trismus or decreased interincisal opening. Diagnostic, IV.
    Plastic and Reconstructive Surgery 02/2012; 129(2):312e-318e. · 3.33 Impact Factor
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    ABSTRACT: Autogenous fat grafting has been observed to alleviate the sequelae of chronic radiodermatitis. To date, no study has replicated this finding in an animal model. The dorsa of adult wild-type FVB mice were shaved and depilated. The dorsal skin was then distracted away from the body and irradiated (45 Gy). Four weeks after irradiation, 1.5-cc fat or sham grafts were placed in the dorsal subcutaneous space. Gross results were analyzed photometrically. The animals were euthanized at 4 and 8 weeks after fat or sham grafting and their dorsal skin was processed for histologic analysis. Hyperpigmentation and ulceration were grossly improved in fat-grafted mice compared with sham-grafted controls. This improvement manifested histologically in a number of ways. For example, epidermal thickness measurements demonstrated decreased thickness in fat-grafted animals at both time points (20.6 ± 1.5 μm versus 55.2 ± 5.6 μm, p = 0.004; 17.6 ± 1.1 μm versus 36.3 ± 6.1 μm, p = 0.039). Picrosirius red staining demonstrated a diminished scar index in fat-treated animals at both time points as well (0.54 ± 0.05 versus 0.74 ± 0.07, p = 0.034; and 0.55 ± 0.06 versus 0.93 ± 0.07, p = 0.001). Fat grafting attenuates inflammation in acute radiodermatitis and slows the progression of fibrosis in chronic radiodermatitis.
    Plastic and Reconstructive Surgery 04/2011; 128(2):363-72. · 3.33 Impact Factor
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    ABSTRACT: Radiation therapy is a cornerstone of oncologic treatment. Skin tolerance is often the limiting factor in radiotherapy. To study these issues and create modalities for intervention, the authors developed a novel murine model of cutaneous radiation injury. The dorsal skin was isolated using a low-pressure clamp and irradiated. Mice were followed for 8 weeks with serial photography and laser Doppler analysis. Sequential skin biopsy specimens were taken and examined histologically. Tensiometry was performed and Young's modulus calculated. High-dose radiation isolated to dorsal skin causes progressive changes in skin perfusion, resulting in dermal thickening, fibrosis, persistent alopecia, and sometimes ulceration. There is increased dermal Smad3 expression, and decreased elasticity and bursting strength. This model of cutaneous radiation injury delivers reproducible localized effects, mimicking the injury pattern seen in human subjects. This technique can be used to study radiation-induced injury to evaluate preventative and therapeutic strategies for these clinical issues.
    Plastic and Reconstructive Surgery 02/2011; 127(2):560-8. · 3.33 Impact Factor
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    ABSTRACT: The inflammatory response to ionizing radiation (IR) includes a proangiogenic effect that could be counterproductive in cancer but can be exploited for treating impaired wound healing. We demonstrate for the first time that IR stimulates hypoxia-inducible factor-1α (HIF-1α) up-regulation in endothelial cells (ECs), a HIF-1α-independent up-regulation of stromal cell-derived factor-1 (SDF-1), as well as endothelial migration, all of which are essential for angiogenesis. 5 Gray IR-induced EC HIF-1α and SDF-1 expression was greater when combined with hypoxia suggesting an additive effect. While small interfering RNA silencing of HIF-1α mRNA and abolition of HIF-1α protein induction down-regulated SDF-1 induction by hypoxia alone, it had little effect on SDF-1 induction by IR, demonstrating an independent pathway. SDF-1-mediated EC migration in hypoxic and/or radiation-treated media showed IR induced strong SDF-1-dependent migration of ECs, augmented by hypoxia. IR activates a novel pathway stimulating EC migration directly through the expression of SDF-1 independent of HIF-1α induction. These observations might be exploited for stimulation of wound healing or controlling tumor angiogenesis.
    Blood 11/2010; 116(18):3669-76. · 9.78 Impact Factor
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    ABSTRACT: Purpose: Fat grafting has been used clinically to alleviate the sequalae of unintended radiation to the skin, however the mechanism of this effect is unknown. We hypothesize that it is related to the delivery of adipose derived stem cells and subsequent neovascularization. Methods: The dorsum of adult wild-type FVB mice was shaved and depilitated. The dorsal skin was then distracted away from the body and radiated (45 Gy) using a Varian 2300 Linear Accelerator. Tissue oximetry and gross photometric analysis were carried out biweekly for the duration of the experiment. 4 weeks following radiation, fat/sham grafts were placed in the dorsal subcutaneous space. Fat grafts consisted of 1.5 cc's of high density lipoaspirate harvested from human donors and processed using the Coleman technique. Sham grafts consisted of 1.5 cc's of sterile saline. Animals were sacrificed at 4 and 8 weeks following fat/sham grafting and their dorsal skin was processed for histologic analysis. Neovascularization was measured by CD31 staining. Fibrosis was assessed using Smad-3 staining, Picrosirius Red staining (Scar-Index), and epidermal thickness measurements. Results: Chronic ulceration and fibrotic skin thickening stabilized 4 weeks post-irradiation. Alopecia, skin color/texture, and ulceration were improved in fat-grafted mice compared to sham-treated controls when analyzed photometrically. Tissue oximetry demonstrated significantly increased blood oxygenation in treated animals beginning two weeks following grafting (8 weeks post graft 77.11.4% vs 68.52.2%, p<0.03). Vascular density of irradiated skin was increased in fat grafted mice compared to radiated controls at 4 weeks (7.30.04% vs 5.20.09%, p<0.01). Relative intensity of Smad-3 staining was significantly decreased in treated animals at both 4 and 8 weeks (2.770.3% vs 4.98.9%, p<0.01; 3.05.2% vs 5.81.3%, p<0.03). Picrosirius Red staining demonstrated a diminished scar-index in treated animals at both 4 and 8 weeks (.540.05 vs .74.07, p<0.03; .55.06 vs .93.07, p<0.01). Finally, epidermal thickness measurements demonstrated a decreased thickness in treated animals at both 4 and 8 weeks as well (20.61.5m vs 55.25.6 m, p<0.01; 17.61.1m vs 36.36.1 m, p<0.04). Conclusion: Human fat grafting has a marked phenotypic and experimental impact on radiation skin damage in a murine model. These affects are related to neovascularization and the downregulation of the TGF-β/Smad3 pathway, which results in restoration of normal skin architecture with decreased fibrosis and epidermal thickness.
    Plastic Surgery: The Meeting 2010; 10/2010
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    ABSTRACT: Pediatric temporomandibular joint dysfunction, resulting from either soft-tissue or skeletal disorders, may be congenital or acquired. Congenital temporomandibular joint disorders are uncommon. The authors review their experience with pediatric temporomandibular joint disorders and propose a new classification system. Clinical records, cephalograms, computed tomographic scans, magnetic resonance images, and pathologic specimens of all pediatric patients (younger than 18 years) with trismus or restricted mandibular excursion from 1976 to 2008 were reviewed. Cases were stratified according to soft-tissue or skeletal pathologic findings; skeletal abnormalities were further characterized as intracapsular or extracapsular. Thirty-eight patients, ranging in age from 1 day to 18 years at diagnosis, were identified with temporomandibular joint disorders. Ten cases (26.3 percent) were attributable to soft-tissue abnormality. The remaining 28 cases (73.7 percent) were attributable to skeletal abnormality, consisting of 14 congenital and 14 acquired cases (50 percent each). Acquired skeletal deformities included 12 intracapsular ankyloses (85.7 percent) and two extracapsular ankylosis (14.3 percent) (extraarticular bone blocks). Congenital skeletal deformities accounted for five intracapsular ankyloses (35.7 percent) and nine extracapsular ankyloses (64.3 percent). On initial survey, the data are consistent with published reports that attribute temporomandibular joint dysfunction to acquired abnormality (i.e., trauma and infection). However, the authors observed a significantly higher percentage (50 percent) of congenital temporomandibular joint skeletal disorders than previously reported. Most congenital cases involved extracapsular abnormality (i.e., coronoid hypertrophy); only a minority of cases had glenoid-condylar fibro-osseous fusion (i.e., intracapsular ankyloses). Because the diagnosis and classification of temporomandibular joint disorders determine treatment options, the authors provide a new classification that characterizes the extent of capsular involvement.
    Plastic and Reconstructive Surgery 10/2010; 126(4):1263-75. · 3.33 Impact Factor
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    ABSTRACT: Diabetes is characterized by several poorly understood phenomena including dysfunctional wound healing and impaired vasculogenesis. p53, a master cell cycle regulator, is upregulated in diabetic wounds and has recently been shown to play a regulatory roles in vasculogenic pathways. We have previously described a novel method to topically silence target genes in a wound bed with small interfering (si)RNA. We hypothesized that silencing p53 results in improved diabetic wound healing and augmentation of vasculogenic mediators. Paired 4-mm stented wounds were created on diabetic db/db mice. Topically applied p53 siRNA, evenly distributed in an agarose matrix, was applied to wounds at postwound day 1 and 7 (matrix alone and nonsense siRNA served as controls). Animals were sacrificed at postwound days 10 and 24. Wound time to closure was photometrically assessed, and wounds were harvested for histology, immunohistochemistry, and immunofluorescence. Vasculogenic cytokine expression was evaluated via Western blot, reverse transcription-polymerase chain reaction, and enzyme-linked immunosorbent assay. The ANOVA/t-test was used to determine significance (p≤ 0.05). Local p53 silencing resulted in faster wound healing with wound closure at 18±1.3 d in the treated group vs. 28±1.0 d in controls. The treated group demonstrated improved wound architecture at each time point while demonstrating near-complete local p53 knockdown. Moreover, treated wounds showed a 1.92-fold increase in CD31 endothelial cell staining over controls. Western blot analysis confirmed near-complete p53 knockdown in treated wounds. At day 10, VEGF secretion (enzyme-linked immunosorbent assay) was significantly increased in treated wounds (109.3±13.9 pg/mL) vs. controls (33.0±3.8 pg/mL) while reverse transcription-polymerase chain reaction demonstrated a 1.86-fold increase in SDF-1 expression in treated wounds vs. controls. This profile was reversed after the treated wounds healed and before closure of controls (day 24). Augmented vasculogenic cytokine profile and endothelial cell markers are associated with improved diabetic wound healing in topical gene therapy with p53 siRNA.
    Wound Repair and Regeneration 10/2010; 18(6):553-9. · 2.76 Impact Factor
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    ABSTRACT: Progenitor cells (PCs) contribute to postnatal neovascularization and tissue repair. Here, we explore the mechanism contributing to decreased diabetic circulating PC number and propose a novel treatment to restore circulating PC number, peripheral neovascularization, and tissue healing. Cutaneous wounds were created on wild-type (C57BL/J6) and diabetic (Lepr(db/db)) mice. Blood and bone marrow PCs were collected at multiple time points. Significantly delayed wound closure in diabetic animals was associated with diminished circulating PC number (1.9-fold increase vs. 7.6-fold increase in lin(-)/sca-1(+)/ckit(+) in wild-type mice; P < 0.01), despite adequate numbers of PCs in the bone marrow at baseline (14.4 +/- 3.2% lin(-)/ckit(+)/sca1(+) vs. 13.5 +/- 2.8% in wild-type). Normal bone marrow PC mobilization in response to peripheral wounding occurred after a necessary switch in bone marrow stromal cell-derived factor-1alpha (SDF-1alpha) expression (40% reduction, P < 0.01). In contrast, a failed switch mechanism in diabetic bone marrow SDF-1alpha expression (2.8% reduction) resulted in impaired PC mobilization. Restoring the bone marrow SDF-1alpha switch (54% reduction, P < 0.01) with plerixafor (Mozobil, formerly known as AMD3100) increased circulating diabetic PC numbers (6.8 +/- 2.0-fold increase in lin(-)/ckit(+), P < 0.05) and significantly improved diabetic wound closure compared with sham-treated controls (32.9 +/- 5.0% vs. 11.9 +/- 3% at day 7, P > 0.05; 73.0 +/- 6.4% vs. 36.5 +/- 7% at day 14, P < 0.05; and 88.0 +/- 5.7% vs. 66.7 +/- 5% at day 21, P > 0.05, respectively). Successful ischemia-induced bone marrow PC mobilization is mediated by a switch in bone marrow SDF-1alpha levels. In diabetes, this switch fails to occur. Plerixafor represents a potential therapeutic agent for improving ischemia-mediated pathology associated with diabetes by reducing bone marrow SDF-1alpha, restoring normal PC mobilization and tissue healing.
    Diabetes 08/2010; 59(8):1974-83. · 7.90 Impact Factor
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    ABSTRACT: Neovascularization involves angiogenesis and vasculogenesis mediated by cytokines and soluble chemokines. The predominant stimulus is ischemia, however, recent data suggest that ionizing radiation (IR) has angiogenic potential. In this study we evaluated whether IR increases vascularity and perfusion in vivo. In wild-type mice, a full-thickness, pedicled skin flap was created and isolated for localized irradiation at a dose of 5 Gy. Serial Doppler analysis of the flap was performed. The skin flaps were then harvested at various time points for vascularity and histologic analysis. Blood was concurrently harvested for serum and hematopoietic progenitor cell population analysis. IR to an ischemic flap augmented the angiogenic cytokines SDF-1 and VEGF. Serum MMP-9 and s-kit levels, which are critical for progenitor cell mobilization, were also increased. When hematopoietic progenitor cells were evaluated by Sca1+/Flk1+ cells, a correlate 2-fold increase was seen compared to controls. When the flaps were examined, both vascularity and perfusion were increased. In this study we demonstrate that local, low-dose IR upregulates angiogenic chemokines and results in progenitor cell mobilization to the systemic circulation. There is a resultant increase in the vascularity of the irradiated flap, suggesting that the pro-angiogenic effects of IR can be harnessed locally.
    Journal of Vascular Research 01/2010; 47(6):472-80. · 2.43 Impact Factor
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    ABSTRACT: The study of human autologous fat grafting has been primarily anecdotal. In this study, the authors aim to develop a murine model that recapitulates human fat grafting to study the fate of injected fat and the cell populations contained within. The authors' method of fat harvesting and refinement has been described previously. The authors injected nude and tie2/lacZ mice with 2 ml of human lipoaspirate placed on the dorsal surface in a multipass, fan-like pattern. Fatty tissue was injected in small volumes of approximately 1/30 ml per withdrawal. The dorsal skin and associated fat was excised at various time points. Sections were stained with hematoxylin and eosin and cytochrome c oxidase IV. Transgenic tie2/lacZ samples were stained with X-galactosidase. At the 8-week time point, volumetric analysis was performed. Volumetric analysis at the 8-week time point showed 82 percent persistence of the original volume. Gross analysis showed it to be healthy, nonfibrotic, and vascularized. Hematoxylin and eosin analysis showed minimal inflammatory or capsular reaction, with viable adipocytes. Fat grafted areas were vascularized with multiple blood vessels. Cytochrome c oxidase IV human-specific stain and beta-galactosidase expression revealed these vessels to be of human origin. The authors have developed a murine model with which to study the fate of injected lipoaspirate. There is a high level of persistence of the grafted human fat, with minimal inflammatory reaction. The fat is viable and vascularized, demonstrating human-derived vessels in a mouse model. This model provides a platform for studying the populations of progenitor cells known to reside in lipoaspirate.
    Plastic and Reconstructive Surgery 08/2009; 124(1):74-81. · 3.33 Impact Factor
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    ABSTRACT: Blood vessel growth is regulated by angiogenic and angiostatic CXC chemokines, and radiation is a vasculogenic stimulus. We investigated the effect of radiation on endothelial cell chemokine signaling, receptor expression, and migration and apoptosis. Human umbilical vein endothelial cells were exposed to a single fraction of 0, 5, or 20 Gy of ionizing radiation (IR). All vasculogenic chemokines (CXCL1–3/5–8) increased 3–13-fold after 5 or 20 Gy IR. 20 Gy induced a marked increase (1.6–4-fold) in angiostatic CXC chemokines. CXCR4 expression increased 3.5 and 7-fold at 48 h after 5 and 20 Gy, respectively. Bone marrow progenitor cell chemotaxis was augmented by conditioned media from cells treated with 5 Gy IR. Whereas 5 Gy markedly decreased intrinsic cell apoptosis (0 Gy = 16% ± 3.6 vs. 5 Gy = 4.5% ± 0.3), 20 Gy increased it (21.4% ± 1.2); a reflection of pro-survival angiogenic chemokine expression. Radiation induces a dose-dependent increase in pro-angiogenic CXC chemokines and CXCR4. In contrast, angiostatic chemokines and apoptosis were induced at higher (20 Gy) radiation doses. Cell migration improved significantly following 5 Gy, but not 20 Gy IR. Collectively, these data suggest that lower doses of IR induce an angiogenic cascade while higher doses produce an angiostatic profile.
    Cytokine 01/2009; · 2.52 Impact Factor
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    ABSTRACT: Since their first review of microsurgical correction of facial contour deformities in 19 patients with craniofacial malformations, the authors have treated an additional 74 patients (n = 93). The authors review indications, choices, safety, efficacy, complications, and technical refinements. A treatment algorithm is presented. A retrospective chart review of all patients who underwent microvascular reconstruction of the face and all patients with craniofacial dysmorphology was performed. Between 1989 and 2004, a total of 93 patients with the following diagnoses were identified: craniofacial microsomia (n = 73), Treacher Collins syndrome (n = 8), and severe orbitofacial cleft (n = 12). All patients underwent microsurgical facial reconstruction with a superficial inferior epigastric, groin, or circumflex scapular flap. Flap revisions, complications, and non-free flap related surgery were reviewed. The mean age at microvascular reconstruction was 11 years (range, 4 to 27 years). Flap choices included the following: superficial inferior epigastric (n = 4), groin (n = 3), and circumflex scapular (n = 105). Seventy-six patients underwent unilateral and 17 patients underwent bilateral (one of 17 simultaneous) reconstructions. Postoperative complications included partial flap loss (n = 1), reexploration (n = 1), hematoma (n = 5), and cellulitis (n = 5). All patients had subjective improvement in facial contour, symmetry, skin tone, and color. Most patients underwent additional non-free flap procedures including mandibular distraction and ear reconstruction. Microsurgical flaps have markedly improved the authors' ability to restore craniofacial contour in patients with craniofacial malformations. In selected patients, the authors choose primary midface augmentation with free vascularized tissue to restore form and function. Microsurgical flaps in patients with craniofacial malformations are safe, effective, and reliable.
    Plastic and Reconstructive Surgery 06/2008; 121(6):368e-378e. · 3.33 Impact Factor