Full-thickness human foreskin transplantation onto nude rats as an in vivo model of acute human wound healing.

Current wound-healing models do not fully duplicate the in vivo human environment. The feasibility of grafting human full-thickness foreskin onto nude rats, as a model of acute wound healing, was evaluated. Incisions were then created on the grafted skin, and wound healing was evaluated. Full-thickness human skin was obtained after elective circumcision and was grafted subcutaneously onto the dorsal thorax of nude rats. At 10 days after transplantation, graft beds were judged for graft viability, on the basis of gross appearance, texture, and adherence. Full-thickness wounds were then made in the foreskin. Graft wounds were left to close by secondary intention. The wounds were allowed to heal for 7 days. Wounds were excised and tested for breaking stress. Histological evaluations included proliferating cell nuclear antigen, factor VIII, hematoxylin and eosin, and trichrome staining. Twenty grafts were performed, with 100 percent viability. Upon incision, all grafts bled freely, indicating a rich vascular supply and tissue viability. Graft viability was confirmed by the presence of proliferating cells in the parabasal stratum of the epithelium. Furthermore, there was evidence of angiogenesis, as confirmed by staining for factor VIII. Breaking stress was evaluated by tensiometry, 7 days after wounding. Histological evaluations revealed viable grafts and active wound-healing events. Full-thickness human skin can be successfully transplanted onto nude rats, providing a larger, more physiological model of human wound healing. This model closely parallels the in vivo situation, providing a promising model for study of the complex biological processes of acute human wound healing, in a reproducible manner.

Infiltrating, moderately differentiated neuroendocrine tumor of the larynx: a brief report.

We report a rare case of moderately differentiated neuroendocrine carcinoma of the larynx. We describe the clinical and pathologic findings relevant to this case, and we review the literature on the pathologic features of this malignancy. We also discuss treatment options.

Cross-linked matrix tissue sealant protects against mortality and hemorrhage in an acute renal injury model in heparinized rats.

PURPOSE: We evaluated the efficacy of a cross-linked matrix tissue sealant compared with oxidized cellulose and electrocautery in an acute renal injury model. MATERIALS AND METHODS: Sprague-Dawley rats underwent partial nephrectomy after intravenous heparin anticoagulation. The cut surface received 1 of 4 therapies, namely no treatment, cross-linked matrix tissue sealant, electrocautery or Surgicel (Johnson & Johnson, New Brunswick, New Jersey) oxidized cellulose. Blood pressure was continually monitored, survival time was determined and total blood loss was quantified in each animal. RESULTS: Animals that received no treatment, electrocautery or oxidized cellulose died within 13 minutes of injury with a decline in blood pressure to 0 mm. Hg. In cross-linked matrix treated rats hemostasis was immediate, resulting in no blood loss after cross-linked matrix application. Mean arterial pressure +/- SEM was maintained at 136 +/- 6 mm. Hg. All cross-linked matrix treated animals survived. CONCLUSIONS: Cross-linked matrix tissue sealant provided immediate hemostasis and protection from a decline in blood pressure after renal trauma in heparinized rats. Cross-linked matrix tissue sealant may benefit patients with severe renal injuries. In the future cross-linked matrix may be useful for long-term partial nephrectomy repair.

Evaluation of octylcyanoacrylate for wound repair of clinical circumcision and human skin incisional healing in a nude rat model.

PURPOSE: Alternative methods of circumcision wound closure have been studied to decrease repair time and complications, and improve cosmesis. This study includes a clinical and a laboratory research portion. Clinical parameters, wound outcome, closure time and operative time were compared for octylcyanoacrylate and suture approximation of circumcision incisions. An in vivo incisional model using human foreskin was used to compare the wound breaking strength of octylcyanoacrylate and suture repair. MATERIALS AND METHODS: Circumcision incisions were closed with suture or octylcyanoacrylate. Wound closure time and operating room time were recorded. Patients were evaluated 1 and 12 weeks postoperatively. Foreskin samples from another group of patients were engrafted to an immunodeficient rat and allowed to heal. Incisions were made in the human skin and the wounds were repaired with sutures or octylcyanoacrylate. After 7 days breaking stress was tested and healing was evaluated by histological testing. RESULTS: Optimal wound healing was noted in all patients 1 week after surgery. Scarring was absent in the octylcyanoacrylate group. Octylcyanoacrylate closure time was significantly shorter than suture time (p <0.001). Mean total operating room time for octylcyanoacrylate plus or minus standard deviation was shorter than for suture (19.4 +/- 0.51 versus 26.9 +/- 0.94 minutes, p <0.001). Octylcyanoacrylate wound breaking stress was equivalent to suture on tensiometry. Histological testing revealed normal healing in all wounds. CONCLUSIONS: Circumcision wounds may be closed by octylcyanoacrylate with shorter wound closure and operative time than by suture. In an animal model of human skin healing, wound breaking stress after octylcyanoacrylate closure was equivalent to suture repair. Octylcyanoacrylate may be a useful alternative to suture closure for circumcision incisions.

Local pharmaceutical release from a new hydrogel implant.

BACKGROUND: Solid hydrogel polymers can act as reservoirs for controlled drug release. The object of this study was to quantify release kinetics for a single example of a class of uniquely structured hydrogels. The polymer of this study belongs to a class of permanent implants that release pharmaceuticals by diffusion from an entangled cross-linked matrix rather than by absorption of the implant by the body. The cross-linked matrix (CLM) of this study is biocompatible and polymerized in situ, forming a solid that is mechanically bonded to the implant site. It can seal tissue as well as deliver drugs at predetermined rates. We evaluated dye and antibiotic egress and assessed release kinetics and retention of antibiotic activity following elution from the CLM. MATERIALS AND METHODS: The prepolymerized test CLM was prepared in two ratios, 6 and 20% prepolymer, in an activating aqueous solution. Aqueous solutions were prepared from dyes of varying molecular weights. Aliquots of prepolymerized test CLM were allowed to solidify and dye release into the supernatant was quantified by spectrophotometry over a 168-h period. Antibiotic solutions were also employed to form solid CLMs. Tetracycline release over time was characterized by spectrophotometry. Antibiotic dosed solid CLMs were placed on agar plates streaked with Escherichia coli and incubated. Growth inhibition was assessed for each antibiotic. RESULTS: In the test CLM, dye and antibiotic release were found to be inversely related to molecular weight and consistent with a diffusion model. CLMs formed from aqueous solutions containing higher molecular weight dyes and antibiotics released those constituents more slowly than lower molecular weight constituents. This finding, as well as the effect on release rate under varying prepolymer concentration, was consistent with a diffusion release mechanism. Antibiotic released from the tissue sealant was shown to be potent by consistent inhibition of E. coli. CONCLUSIONS: Pharmaceutical release by a representative CLM was found to be controllable by varying the concentration of the pharmaceutical in the activating aqueous solution. The polymerization and release mechanisms did not degrade antibiotic biologic activity. CLMs may be a general class of biocompatible polymers that can locally deliver clinically useful biologics, the release kinetics of which are unaffected by the variability of implant absorption/inflammation mechanisms.

Ex vivo evaluation of human fetal membrane closure.

BACKGROUND AND OBJECTIVE: This study compares stress and leak point pressure of human fetal membranes following closure with suture, laser welding, or a new tissue sealant, SynthaSeal. STUDY DESIGN/MATERIALS AND METHODS: Samples of fetal membrane were bisected and repaired with suture, laser welding with albumin solders, or a tissue sealant. Representative tissue samples were assessed by histology. Anastomotic strength was evaluated by tensiometry. Additionally, leak pressure was measured after membrane samples were placed onto an infusion pump/pressure transducer, incised, and repaired as above. RESULTS: Membrane stress was strongest (P<0.001) for the tissue sealant group. Sutured samples were stronger than laser-welded samples. Membrane leak pressure was greatest for the tissue sealant group. The suture group demonstrated a higher leak pressure than the laser-welded group. CONCLUSIONS: Human fetal membranes were not suited for repair with laser welding under the conditions tested. A new tissue sealant, SynthaSeal, may provide a simple, effective method for membrane closure following fetoscopy, amniocentesis, and open fetal surgery.

Transforming growth factor-beta2 (TGF-beta2) reverses the inhibitory effects of fibrin sealant on cutaneous wound repair in the pig.

Tensile strength of 2-cm, full-thickness, surgically incised porcine skin wounds sealed with fibrin sealant was enhanced compared to conventionally sutured wounds at 6 hours postwounding, but was significantly reduced after 3 days. Supplementation of fibrin sealant with transforming growth factor-beta2 (TGF-beta2) reversed the inhibitory effects of fibrin sealant on tensile strength at 3 days, and enhanced tensile strength at 7 days compared to suture or fibrin sealant alone. By 14 days, the tensile strengths of all wounds were similar, although wounds treated with fibrin sealant supplemented with TGF-beta2 showed a small, but statistically significant, improvement in wound strength compared to wounds treated with fibrin sealant alone. Histological assessment at day 7 revealed significant remnants of fibrin sealant at the wound site following fibrin sealant treatment alone, while wounds treated with fibrin sealant supplemented with TGF-beta2 or suture exhibited fibroblast infiltration and extracellular matrix deposition. At day 7, TGF-beta was immunolocalized in the base and margins of only wounds treated with fibrin sealant supplemented with TGF-beta2. A significant increase in matrix metalloproteinase-9 activity was found in fibrin sealant-treated wounds at day 7 as compared to sutured wounds. Addition of TGF-beta to the fibrin sealant suppressed the up-regulation of matrix metalloproteinase-9 in these wounds. These results suggest that fibrin sealant supplemented with TGF-beta may provide superior wound healing as compared to fibrin sealant alone.