Christopher C Chang

Yale-New Haven Hospital, New Haven, Connecticut, United States

Are you Christopher C Chang?

Claim your profile

Publications (29)77.94 Total impact

  • Mark W Maxfield · Christopher C Chang · Deepak Narayan · Anthony W Kim
    [Show abstract] [Hide abstract]
    ABSTRACT: Pleomorphic liposarcomas are rare entities with less than 40 cases diagnosed each year, of which a small proportion arise from the chest wall. Optimal management involves wide local resection with negative margins. We describe the case of a 69-year-old gentleman with a chronically growing chest wall mass. After computed tomography and positron-emission tomography, the mass was resected. Chest wall reconstruction was performed with mesh and a transverse rectus abdominis myocutaneous flap. The patient did well postoperatively, with no evidence of recurrence at 10 months.
    No preview · Article · Nov 2014 · Asian cardiovascular & thoracic annals
  • Philipp Metzler · Erik J. Geiger · Christopher C. Chang · Derek M. Steinbacher
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose The impact of surgically assisted maxillary expansion (SAME) on facial soft tissue structures has not been adequately studied using 3-dimensional objective analysis. The purpose of this study was to analyze nasolabial soft tissue following SAME using 3D photo technology. Methods This is a retrospective cohort study of patients undergoing surgically assisted maxillary expansion (SAME) in which pre- and postexpansion 3D photographs (3D VECTRA photosystem, Canfield, Fairfield, NJ) were analyzed. Nasolabial anthropometric measurements were performed using the 3D post-processing software (Mirror). A follow-up period of at least six months was required for final evaluation. Two observers verified the landmarks on each data set before measuring. Statistical analysis involved the paired t-test, Simes correction for multiple comparisons, and repeated measures ANCOVA to control for age, gender, and the time lag between pre- and postoperative assessments. Results A total of twelve patients (twenty-four photogrammetric data sets) were included. The male/ female ratio was 0.5, with a mean age of 17.3 years. Nasal changes following SAME showed significant increases (p<0.05) in the alar width (from 33.1 to 34.5mm), in sill width (from 9.2 to 9.7mm), and in columella projection (from 94.1 to 95.1mm) after Simes correction. ANCOVA showed a significant increase in alar base width. Distinct changes in nostril shape and dimension were found, but lacked statistical significance. Conclusion 3-Dimensional analysis demonstrates widening of the alar width and alar base width following SAME. The magnitude of nasal change parallels that of expansion at the piriform aperture.
    No preview · Article · Oct 2014 · Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons
  • Erik J Geiger · Bryce A Basques · Christopher C Chang · Andre W Alcon · Deepak Narayan
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Intraoperative brachytherapy (IOBT) to the tumor bed coupled with surgery has been shown to increase survival and to improve locoregional disease control after head and neck tumor extirpation. Flap reconstruction attempts to restore patient anatomy, while also covering the radioactive implants. The purpose of this study was to better characterize the wound healing complications experienced by patients undergoing reconstruction in the setting of IOBT after tumor ablation, as well as to identify risk factors predicting complications and the need for reoperation. Methods: A retrospective chart review of patients receiving IOBT for head and neck cancer at Yale-New Haven Hospital between 2005 and 2013 was conducted. Patient, tumor, treatment, and reconstructive details were recorded. The number and type of flap complications, as well as instances in which patients had to be taken back to the operating room, were documented. Bivariate and multivariate logistic regressions were performed to identify risk factors associated with the occurrence of 1 or more flap complications, as well as the need for reoperation. Results: Ninety-three patients aged 31 to 93 years (mean, 64 ± 12 years) who underwent IOBT with flap reconstruction were included in the study. Of these, 94% had a prior history of radiation (external beam or previous IOBT). Overall, 48 (51.6%) patients experienced at least 1 flap complication, the most common of which was flap dehiscence (32% of patients). Thirty-two patients (34% of the cohort) had to be taken back to the operating room at least once for flap debridement or a revision procedure. On multivariate analysis, only the placement of mandibular hardware during flap reconstruction was significantly associated with the risk of developing any type of flap complication (odds ratio, 3.7; P = 0.009) or with subsequent return to the operating room (odds ratio, 3.9; P = 0.012). Conclusions: This study, the largest of its kind, demonstrated a very high complication rate for flaps used to cover brachytherapy implants in this patient cohort. However, many of the patient complications could be managed nonoperatively. Avoiding the use of mandibular hardware with IOBT suggests a method of reducing complications with reconstruction.
    No preview · Article · Jul 2014 · Annals of Plastic Surgery
  • [Show abstract] [Hide abstract]
    ABSTRACT: Le Fort I advancement induces soft tissue changes to the nasolabial region. The correlation of sagittal skeletal movement to soft tissue alteration has been studied using 2D methods. However, the influence of maxillary advancement has not been adequately assessed using three-dimensional means. The purpose of this study is to analyze nasolabial changes following Le Fort I advancement using 3D photometric measurements. Patient demographic information and their amount of advancement were tabulated. Pre- and postoperative 3D photographs (3D VECTRA photosystem, Canfield, Fairfield, NJ) were recorded. Nasolabial anthropometric measurements were performed using the corresponding 3D post-processing software (Mirror). Six month minimum follow-up elapsed before final evaluation. Forty-four 3D photo data sets were included. Mean maxillary advancement was 5.5 (±1.9) mm. Male/female ratio was 0.7 with a mean age of 16.7 years. Significant increases (p < 0.0001) were seen in the alar base, alar widths, nostril width, and in the soft triangle and lateral alar angles. Significant decreases (p < 0.0001) were noted in the nasofrontal angle and in nostril height. A significant (p < 0.05) increase of the nasal tip, columella and upper lip projection was seen. Philtral height showed no significant changes (p > 0.05) after maxillary advancement. No significant correlation (p > 0.05) between the degree of soft tissue changes and the amount of maxillary advancement was found. Le Fort I advancement significantly impacts the nasolabial soft tissue envelope. The 3D soft tissue changes are predictable and similar for any advancement up to 10 mm.
    No preview · Article · Apr 2014 · Journal of Plastic Reconstructive & Aesthetic Surgery
  • Peter W Hashim · Anup Patel · Christopher C Chang · Joel S Beckett · John A Persing
    [Show abstract] [Hide abstract]
    ABSTRACT: Metopic synostosis represents an increasingly prevalent form of nonsyndromic craniosynostosis. Premature fusion of the metopic suture classically results in trigonocephaly, hypotelorism, temporal narrowing, and a pronounced midline forehead ridge. However, as varying degrees of skull deformity exist, there is confusion regarding the appropriate management for an infant with a metopic ridge. We report on a 2-month-old infant with clinical manifestations of metopic synostosis but with a patent metopic suture documented on computed tomography scan. We examine the implications for management related to fusion of the suture, age of the patient, and severity of the head deformity.
    No preview · Article · Jan 2014 · The Journal of craniofacial surgery
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Le Fort I advancement induces soft tissue changes to the nasolabial region. The correlation of sagittal skeletal movement to soft tissue alteration has been studied using 2D methods. However, the influence of maxillary advancement has not been adequately assessed using three-dimensional means. The purpose of this study is to analyze nasolabial changes following Le Fort I advancement using 3D photometric measurements. Methods Patient demographic information and their amount of advancement were tabulated. Pre- and postoperative 3D photographs (3D VECTRA photosystem, Canfield, Fairfield, NJ) were recorded. Nasolabial anthropometric measurements were performed using the corresponding 3D post-processing software (Mirror). Six month minimum follow-up elapsed before final evaluation. Results Forty-four 3D photo data sets were included. Mean maxillary advancement was 5.5 (±1.9) mm. Male/ female ratio was 0.7 with a mean age of 16.7 years. Significant increases (p<0.0001) were seen in the alar base, alar widths, nostril width, and in the soft triangle and lateral alar angles. Significant decreases (p<0.0001) were noted in the nasofrontal angle and in nostril height. A significant (p<0.05) increase of the nasal tip, columella and upper lip projection was seen. Philtral height showed no significant changes (p>0.05) after maxillary advancement. No significant correlation (p>0.05) between the degree of soft tissue changes and the amount of maxillary advancement was found. Conclusion Le Fort I advancement significantly impacts the nasolabial soft tissue envelope. The 3D soft tissue changes are predictable and similar for any advancement up to 10 mm.
    No preview · Article · Jan 2014 · Journal of Plastic Reconstructive & Aesthetic Surgery
  • Miles J Pfaff · Christopher C Chang · Anup Patel · Derek M Steinbacher
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Malposition of the lower eyelid may disrupt facial aesthetics and impair proper eyelid function. Multiple techniques have been proposed to restore lower eyelid position. The purpose of this study is to report on a modified bridge of bone canthopexy technique and assess its effect on lower eyelid and palpebral fissure restoration. Methods: A retrospective chart review was conducted. Pre- and post-operative photographs of patients were evaluated by a blinded observer. Pair-wise and chi-square tests were conducted with an observed p-value of 0.05 or less considered statistically significant. Results: 12 patients (7 females) with a mean age of 42 (range = 7-87) were included. Canthal tilt and scleral show decreased significantly following surgery (p = 0.05), and the eye fissure index and inferior coverage of the iris approached significance (p = 0.16 and p = 0.07, respectively). Two minor complications were encountered in our series. Conclusion: The modified bridge of bone canthopexy is a safe and effective technique for alteration of the lower eyelid and is broadly applicable to all causes of negative canthal angulation. Further studies are necessary to test the longevity and stability of this procedure.
    No preview · Article · Feb 2013 · Journal of Plastic Reconstructive & Aesthetic Surgery
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Treacher Collins syndrome (TCS) is a facial dysostosis, the hallmark being bilateral malar hypoplasia. The purpose of this study is to morphologically classify the TCS malar deformity and to volumetrically characterise both the TCS zygoma and masseter muscle, including for left-right symmetry, compared to controls. We hypothesise that the TCS zygoma will be smaller than controls and zygomatic deficiency will portend masseteric hypoplasia. Methods: Demographic and computed tomography (CT) data were recorded. The CT scans were converted into three-dimensional facial renderings, and the zygomatic morphology was grossly evaluated. A classification was reported based on malar structure and presence/absence of normal zygomaticomaxillary complex articulations. The zygoma and masseter muscles were then digitally isolated using 3-D planning software (Materialise, Leuven, Belgium). Volumes and sidedness ratios were calculated and compared using two-sided t-tests. Results: 58 sides were identified (24 TCS: 34 controls), mean age of 60.0 months and normally distributed. The phenotypic dysmorphology was graded as mild, moderate or severe (I, II and III, respectively). TCS malar and masseteric volumes were significantly smaller than controls (p < 0.0001 in both cases). The TCS zygomatic side-side symmetry ratio was 0.66 ± 0.28, compared to 0.97 ± 0.02 for controls (p = 0.002). The TCS masseteric side-side ratio was 0.74 ± 0.20, compared to 0.92 ± 0.09 for controls (p = 0.001). Conclusions: A range of zygomatic hypoplasia exists in TCS (mild-severe). The decrease in malar volume occurs in concert with masseteric hypoplasia, and the left and right sides are not equally affected.
    Full-text · Article · Aug 2012 · Journal of Plastic Reconstructive & Aesthetic Surgery
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: Temporomandibular joint malformation is a complex deformity in Treacher-Collins syndrome (TCS); however, it is not well characterized. This study aimed to better clarify this pathology by volumetrically assessing the mandibular condyle in patients with TCS compared with normal controls and the relative contribution of the condyle to hemimandibular volume. MATERIALS AND METHODS: A retrospective, cross-sectional analysis of pediatric patients with TCS and unaffected controls was performed. The study sample was comprised of Treacher Collins patients. The predictor variable in this study was disease status (TCS diagnosis vs control), and the outcome variable was condylar volume. Demographic information was collected, and 3-dimensional computed tomographic data were analyzed by computerized segmentation (Materialise). Volumes were obtained for TCS condyles and compared with age-matched controls using the Student t test. RESULTS: Three-dimensional computed tomographic scans were identified in 10 patients with TCS (20 sides) and 14 control subjects (28 sides). The TCS group included 4 female and 6 male patients (age, 0.3 to 213 mo; average age, 66.5 mo). The control cohort included 7 female and 7 male subjects (average age, 68.8 mo). Evaluation of the mandibular condyle showed that patients with TCS had a significantly smaller condylar volume than control patients (TCS, 178.28 ± 182.74 mm(3); control, 863.55 ± 367.20 mm(3); P < .001). Additional intragroup analysis showed no significant differences between the left and right condylar volumes in the TCS group (P = .267). In addition, the condyle for patients with TCS represented a smaller proportion of hemimandibular volume compared with controls (1.37% vs 4.19%, respectively; P < .001). CONCLUSIONS: The results of the this study suggest that condylar volumes are significantly smaller in patients with TCS compared with age-matched controls, and the condyle represents a smaller fraction of the total mandibular volume for patients with TCS than in unaffected children. In addition, there is considerable variability of condylar size in patients with TCS. These facts portend treatment decisions because a functional temporomandibular joint is necessary and may need to be reconstructed as a first stage before effective implementation of distraction procedures.
    Full-text · Article · Jul 2012 · Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons
  • Source
    Christopher C Chang · Derek M Steinbacher
    [Show abstract] [Hide abstract]
    ABSTRACT: Treacher Collins syndrome is a genetic disorder resulting in congenital craniofacial malformation. Patients typically present with downslanting palpebral fissures, lower eyelid colobomas, microtia, and malar and mandibular hypoplasia. This autosomal dominant disorder has a variable degree of phenotypic expression, and patients have no associated developmental delay or neurologic disease. Care for these patients requires a multidisciplinary team from birth through adulthood. Proper planning, counseling and surgical techniques are essential for optimizing patient outcomes. Here the authors review the features, genetics, and treatment of Treacher Collins syndrome.
    Preview · Article · May 2012 · Seminars in Plastic Surgery
  • Anup Patel · Ajul Shah · James E Clune · Christopher C Chang

    No preview · Article · Apr 2012 · Plastic and Reconstructive Surgery
  • Anup Patel · Christopher C Chang · Jordan S Terner · Charles T Tuggle · John A Persing
    [Show abstract] [Hide abstract]
    ABSTRACT: Orbital rim deficits are a feature of metopic, unilateral coronal, and bilateral coronal craniosynostosis. Several procedures have been developed to address this issue, but relapse to the preoperative hypoplastic deformity and stunted growth of the fronto-orbital region are common. The authors describe a technique modification of the conventional lateral canthal advancement referred to as the orbital rim "tilt" procedure, which aims to preserve inferior bony support for the orbital rim and create projection with optimal proclination of the fronto-orbital complex.
    No preview · Article · Mar 2012 · The Journal of craniofacial surgery
  • Christopher C Chang · Derek M Steinbacher
    [Show abstract] [Hide abstract]
    ABSTRACT: Occlusal splints are used in craniomaxillofacial surgery to control the dental-bearing bony structures of the midface and mandible. They are created to guide the mobile bone segments into position based on the ideal or planned dental and facial relationships. For conventional orthognathic cases and maxillofacial trauma scenarios involving the dentition, a nasal endotracheal tube is required, allowing the teeth to be closed into intermaxillary fixation. However, in situations where access to the nasal cavity is required, such as concurrent rhinoplasty, or when higher osteotomies involving the midface are performed requiring advancement or manipulation of the nasal region, the nasal tube needs to be converted into an oral tube (J Clin Anesth 2011;23:342). This requires time and inconvenience and is a potentially dangerous maneuver in the setting of existing surgical edema, fluids, and manipulation. We report on a novel oral splint design allowing for both intermaxillary fixation to be established using an oral endotracheal tube while allowing for manipulation of the midface via the nasal cavity and not requiring a tube change intraoperatively.
    No preview · Article · Mar 2012 · The Journal of craniofacial surgery
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Feb 2012 · Plastic and Reconstructive Surgery
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Apr 2011 · Plastic and Reconstructive Surgery
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Feb 2011 · Plastic and Reconstructive Surgery
  • Source
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Nov 2010 · Blood
  • Anup Patel · James E Clune · Antonio Forte · Christopher C Chang

    No preview · Article · Nov 2010 · Plastic and Reconstructive Surgery
  • [Show abstract] [Hide abstract]
    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.
    No preview · Conference Paper · Oct 2010
  • Source
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Oct 2010 · Wound Repair and Regeneration

Publication Stats

260 Citations
77.94 Total Impact Points

Institutions

  • 2010-2014
    • Yale-New Haven Hospital
      • Department of Laboratory Medicine
      New Haven, Connecticut, United States
    • Yale University
      • Department of Surgery
      New Haven, Connecticut, United States
  • 2008-2011
    • NYU Langone Medical Center
      New York, New York, United States
  • 2009-2010
    • American Society of Ophthalmic Plastic and Reconstructive Surgery
      New York City, New York, United States
  • 2008-2010
    • CUNY Graduate Center
      New York, New York, United States