Antonio Espinosa-de-los-Monteros

Promotion of incisional wound repair by human mesenchymal stem cell transplantation.

Abstract:  The purpose of this study was to determine the effect of transplanted human mesenchymal stem cells (hMSCs) on wound healing. In this model, full‐thickness cutaneous wounds were created by incision in the skin of adult New Zealand white rabbits and treated by transplanted hMSCs into the wounds. Wound healing was evaluated by histological analysis and tensiometry over time. A total of 15 New Zealand white rabbits with 10 wounds per animal were examined in this study. Animals were treated with hMSCs and euthanised at 3, 7, 14, 21 and 80 days after manipulation. The hMSCs were labelled with a fluorescent dye (CM‐DiI), suspended in phosphate‐buffered saline and used to treat full‐thickness incisional wounds in rabbit skin. Tensiometry and histology were used to characterise the wound‐healing rate of the incisional wounds. These results showed that transplanted hMSCs significantly inhibited scar formation and increased the tensile strength of the wounds. Importantly, MSCs from genetically unrelated donors did not appear to induce an immunologic response. In conclusion, human mesenchymal stem cell therapy is a viable approach to significantly affect the course of normal cutaneous wound healing and significantly increase the tensile strength.

Athletic pubalgia: definition and surgical treatment.

Introduction:Athletic pubalgia, or “sports hernia,” affects people actively engaged in sports. Previously described in high-performance athletes, it can occur in recreational athletes. It presents with inguinal pain exacerbated with physical activity. Examination reveals absence of a hernia with pubic point tenderness accentuated by resisted adduction of the hip. Diagnosis is by history and physical findings. Treatment with an internal oblique flap reinforced with mesh alleviates symptoms. Methods:A retrospective review from December 1998 to November 2004 for patients with athletic pubalgia who underwent operative repair was performed. Descriptive variables included age, gender, laterality, sport, time to presentation, outcome, anatomy, and length of follow-up. Results:Twelve patients, 1 female, with median age 25 years were evaluated. Activities included running (33%), basketball (25%), soccer (17%), football (17%), and baseball (8%). The majority were recreational athletes (50%). Median time to presentation was 9 months, with a median 4 months of follow-up. The most common intraoperative findings were nonspecific attenuation of the inguinal floor and cord lipomas. All underwent open inguinal repair, with 9 being reinforced with mesh. Four had adductor tenotomy. Results were 83.3% excellent and 16.7% satisfactory. All returned to sports. Conclusion:Diagnosis of athletic pubalgia can be elusive, but is established by history and physical examination. It can be found in recreational athletes. An open approach using mesh relieves the pain and restores activity.

The Importance of Radical Intravelar Veloplasty during Two-flap Palatoplasty

Background: The purpose of this study was to compare the two-flap palatoplasty technique for cleft palate repair, with and without radical intravelar veloplasty, with special emphasis on the fistula rate and speech outcome. Methods: A retrospective, time-series cohort of 213 consecutive patients with primary two-flap palatoplasty before and after the introduction of a radical intravelar veloplasty was studied. The main outcome measures were immediate postoperative complications, oronasal fistula rate, and speech. A perceptual speech evaluation was performed by two speech pathologists and included hypernasality, nasal emission, articulation, intelligibility, and overall velopharyngeal competence. The need for secondary palate surgery for velopharyngeal insufficiency was also analyzed. Results: There were no differences in postoperative complications between the two study groups. Postoperative morbidity occurred in six patients (2.8 percent) and consisted of two patients with respiratory compromise, two patients who required reoperation for bleeding, and two patients with oronasal fistula. Perceptual speech evaluation demonstrated significantly better speech outcomes (81.9 percent versus 49.5 percent, p < 0.001) and a significantly lower rate of secondary palate surgery for velopharyngeal insufficiency (29 percent versus 6.7 percent, p = 0.008) in the radical intravelar veloplasty group. The most important predictive factor of speech outcome was the addition of a radical intravelar veloplasty (odds ratio, 0.175; 95 percent confidence interval, 0.039 to 0.785). Conclusions: Despite study design limitations, such as experience bias and follow-up differences, this study demonstrates that radical intravelar veloplasty may enhance the functional results of the two-flap palatoplasty without increasing postoperative morbidity. A novel classification of the muscle repair is proposed based on the amount of muscle dissection and retropositioning.

Effect of adenoviral mediated overexpression of fibromodulin on human dermal fibroblasts and scar formation in full-thickness incisional wounds

Fibromodulin, a member of the small leucine-rich proteoglycan family, has been recently suggested as a biologically significant mediator of fetal scarless repair. To assess the role of fibromodulin in the tissue remodeling, we constructed an adenoviral vector expressing human fibromodulin cDNA. We evaluated the effect of adenovirus-mediated overexpression of fibromodulin in vitro on transforming growth factors and metalloproteinases in fibroblasts and in vivo on full-thickness incisional wounds in a rabbit model. In vitro, we found that Ad-Fibromodulin induced a decrease of expression of TGF-β1 and TGF-β2 precursor proteins, but an increase in expression of TGF-β3 precursor protein and TGF-β type II receptor. In addition, fibromodulin overexpression resulted in decreased MMP-1 and MMP-3 protein secretion but increased MMP-2, TIMP-1, and TIMP-2 secretion, whereas MMP-9 and MMP-13 were not influenced by fibromodulin overexpression. In vivo evaluation by histopathology and tensile strength demonstrated that Ad-Fibromodulin administration could ameliorate wound healing in incisional wounds. In conclusion, although the mechanism of scar formation in adult wounds remains incompletely understood, we found that fibromodulin overexpression improves wound healing in vivo, suggesting that fibromodulin may be a key mediator in reduced scarring.

Abdominoplasty with Total Abdominal Liposuction for Patients with Massive Weight Loss

BackgroundMassive weight loss after bariatric surgery is associated with significant skin excess, laxity, and ptosis over the abdomen. Good results have been achieved with abdominoplasty and circumferential lipectomy. However, blood transfusions are sometimes needed, and patients may require long hospital stays. Furthermore, morbidity rates are high. Total abdominal liposuction performed with abdominoplasty allows for the preservation of lymphatic vessels below Scarpa’s fascia and eliminates the need for upper flap undermining. This study aimed to evaluate this technique in patients with anterior abdominal redundancy attributable to massive weight loss after bariatric surgery.MethodsThe charts of 60 patients treated between December 2001 and October 2004 were retrospectively reviewed. All the patients had undergone previous bariatric surgery as well as subsequent total abdominal liposuction and abdominoplasty.ResultsThe average amount of wetting solution used was 3.1 l, and the average total aspirate was 2.5 l. The mean pannus weight was 3,649 g, and the average dimension was 48 × 25 × 6 cm. No patient required a blood transfusion. The median in-hospital stay was 1 day, with 42% of the patients treated as outpatients. The median follow-up period was 3 months. Morbidity was 22%. Factors associated with the development of complications were weight of the pannus, transverse dimension of the pannus, and body mass index. All the patients were satisfied with the results.ConclusionsTotal abdominal liposuction followed by abdominoplasty is adequate treatment for anterior abdominal redundancy for patients with massive weight loss.

Strategies to enhance transductional efficiency of adenoviral‐based gene transfer to primary human fibroblasts and keratinocytes as a platform in dermal wounds

Genetically modified keratinocytes and fibroblasts are suitable for delivery of therapeutic genes capable of modifying the wound healing process. However, efficient gene delivery is a prerequisite for successful gene therapy of wounds. Whereas adenoviral vectors (Ads) exhibit superior levels of in vivo gene transfer, their transductional efficiency to cells resident within wounds may nonetheless be suboptimal, due to deficiency of the primary adenovirus receptor, coxsackie‐adenovirus receptor (CAR). We explored CAR‐independent transduction to fibroblasts and keratinocytes using a panel of CAR‐independent fiber‐modified Ads to determine enhancement of infectivity. These fiber‐modified adenoviral vectors included Ad 3 knob (Ad5/3), canine Ad serotype 2 knob (Ad5CAV‐2), RGD (Ad5.RGD), polylysine (Ad5.pK7), or both RGD and polylysine (Ad5.RGD.pK7). To evaluate whether transduction efficiencies of the fiber‐modified adenoviral vectors correlated with the expression of their putative receptors on keratinocytes and fibroblasts, we analyzed the mRNA levels of CAR, αυ integrin, syndecan‐1, and glypican‐1 using quantitative polymerase chain reaction. Analysis of luciferase and green fluorescent protein transgene expression showed superior transduction efficiency of Ad5.pK7 in keratinocytes and Ad5.RGD.pK7 in fibroblasts. mRNA expression of αυ integrin, syndecan‐1 and glypican‐1 was significantly higher in primary fibroblasts than CAR. In keratinocytes, syndecan‐1 expression was significantly higher than all the other receptors tested. Significant infectivity enhancement was achieved in keratinocytes and fibroblasts using fiber‐modified adenoviral vectors. These strategies to enhance infectivity may help to achieve higher clinical efficacy of wound gene therapy.