The healing effects of L-carnitine and spongostan on cartilage defect in rat model.

PURPOSE: We aimed to determine the effect of L-carnitine and spongostan on cartilage healing in an experimental animal model with a full-thickness cartilage defect. METHODS: In the study 32 Sprague-Dawley rats were divided into four groups in equal numbers. A cartilage defect with a diameter of 1 mm and a depth of 3 mm was created in the femoral intercondylar region of rats in groups A, B, and C. Group A received no treatment in the defective area. Group B received treatment with spongostan. Group C received treatment with spongostan soaked in L-carnitine. Group D served as the healthy control group. The rats were euthanized 6 weeks after the treatment. Histological evaluation of the condyles was done with the modified Mankin scoring. RESULTS: In the histopathological imaging of the cartilage structure, it was observed that in group A, there was complete disorganization and cellular structure was completely absent up to the subchondral bone. In group B, moderate structural improvement, partially intact appearance in border integrity and mostly diffuse hypercellularity were observed. In group C, a near-normal healing, a completely intact appearance in boundary integrities and normal or hypercellularity in cellular structure were observed. The total score of the modified Mankin decreases numerically from A to D. There was no statistically significant difference observed between the A-B (p = 0.176), C-D (p = 0.145), and C-B (p = 0.580) groups, while significant differences were detected between the A-C (p = 0.004), B-D (p = 0.007), and A-D (p = 0.000) groups. CONCLUSION: It has been known that mitochondrial activity is reduced in the osteoarthritis, and as a result, decrease in cellular activity occurs with ATP synthesis. For this reason, we found that L-carnitine, which we expect to stimulate cell proliferation by stimulating ATP synthesis, makes a positive contribution to cartilage healing, as expected. It has been found that combining spongostan with L-carnitine for the treatment of cartilage healing, instead of applying spongostan alone, provides near-normal healing.

The effects of different packing materials on healing and hearing after trauma to middle ear mucosa, an experimental study in rats.

PURPOSE: To compare the performance of Spongostan, Otopore, Spongostan soaked with dexamethasone and Spongostan soaked with Hyaluronic acid (HA) as middle ear packing material after mucosal trauma. METHODS: Twenty rats were divided into 4 groups. In control group (group 1), the middle ear cavities of animals were bilaterally packed with Spongostan; in group 2, with Otopore; in group 3, with Spongostan soaked with dexamethasone; and in group 4, with Spongostan soaked with HA. Auditory brainstem responses (ABRs) were performed preoperatively and 1 and 6 weeks postoperatively. Histological analyses were performed to evaluate the inflammatory reaction and wound healing in the middle ear cavity. RESULTS: ABR recordings demonstrate that threshold level changes from baseline were minor in Otopore and Spongostan soaked with dexamethasone packed ears. Threshold levels were higher in the Spongostan and Spongostan soaked with HA packed ears compared with both Otopore and Spongostan soaked with dexamethasone packed ears. Histological analyses showed that Spongostan caused inflammation more intense than Otopore and Spongostan soaked with dexamethasone. Residual material at postoperative week 6, new bone formation and adhesion were common in the Spongostan group compared with other groups. Fibrosis was more common in Spongostan group compared with other groups but the difference was not significant. CONCLUSION: Otopore appears to be safe and effective for use in otologic surgery. The inflammation, adhesion and new bone formation decreased when Spongostan was used with steroid or HA, when compared to Spongostan alone.

Histopathologic Analysis of Tamoxifen on Epidural Fibrosis.

BACKGROUND: Epidural fibrosis is a challenging topic in spinal surgery. This phenomenon constitutes one of the main reasons behind postlaminectomy syndrome or failed back surgery syndrome, which leads to persistent back and leg pain in association with compression and/or stretching the nerve root or the dura. The exact mechanism of action in epidural fibrosis is complex and remains uncertain. Excessive deposition of collagen, fibronectin, and dermatan sulfate, known as the "extracellular matrix," and decrease of tissue cellularity results in epidural fibrosis. The most investigated and important actor in epidural fibrosis as well as in other forms of aberrant wound healing is presumed to be transforming growth factor-1ß formation. Tamoxifen (TAM), a synthetic nonsteroidal antiestrogen used in breast cancer, is also effective in inhibiting fibroblast proliferation via downregulation of transforming growth factor-1ß. METHODS: Twenty-four adult male rats were randomly divided into 3 groups. Laminectomy was the sole intervention in the control group. Spongostan was placed in the operation lodge after laminectomy in the second group. In the treatment group, TAM was administrated orally after laminectomy. Epidural fibrosis, dural thickness, inflammatory response, and arachnoidal involvement were evaluated and graded histopathologically. RESULTS: Epidural fibrosis, dural thickness, and inflammatory response in the subjects treated with TAM were significantly less than in the control and Spongostan group and the differences were statistically significant. Although arachnoidal involvement was observed in a subject in the TAM group, the differences between all groups weren't statistically significant. CONCLUSIONS: Tamoxifen reduced epidural fibrosis, dural thickness, and inflammatory response after laminectomy in rats.

A new model for dura mater healing: human dural fibroblast culture.

OBJECTIVE: Dura mater healing is crucial to prevent cerebrospinal fluid (CSF) leaks after neurosurgical procedures. Biological mechanisms leading to dural closure are only partially understood and have been studied in animals exclusively. We studied an in vitro model of dural closure which uses human cells. MATERIALS AND METHODS: We used human dura intended for disposal after surgery. Explant primary cultures were performed. Cells were characterized through common staining and immunohistochemistry. A cell growth curve was elaborated and the effect of dexamethasone on cell count was assessed. Spongostan®, oxidized regenerated cellulose and autologous plastic materials were also evaluated for their effect on cellular growth. RESULTS: All specimens showed growth in fusiform cells, which project pseudopods and fuse into spindles. Cells showed desmin and vimentin positivity, and were negative for all the other stains, behaving phenotypically like fibroblasts. No collagen base was necessary for cell growth. Dexamethasone decreased cell count in the primary culture as well as in the explant, and reduced the cell proliferation marker Ki-67. Spongostan® was successfully used as a graft, and fibroblast cultures were additionally developed with muscle, pericranium, galea, and fascia. Oxidized cellulose induced cell death by lowering the pH of the solution. DISCUSSION: According to the findings, unlike mini-pigs and rabbits, in humans, dural fibroblast sensitivity to collagen seems to be lower. Dexamethasone inhibits fibroblast invasion, which is the biological base of wound dehiscence in cranial surgery. Although Spongostan is useful, Surgicel® can lower the media pH, thereby inhibiting cellular growth.

Evaluation of a new foam to increase skin hydration of the foot in type 2 diabetes: a pilot study.

The aim of the present study was to evaluate the efficacy of a new product (Neuropad repair foam(®)) in promoting skin hydration of the foot in type 2 diabetes. Included in this study were 20 type 2 diabetic patients (10 men, mean age 61·40 ± 2·44 years). Patients applied Neuropad repair foam(®) on the plantar aspect of the right foot twice daily. No agent was applied on the left foot. Patients were examined at baseline, after 7 treatment days and after 14 treatment days. Evaluation of skin dryness was performed by means of the Multi Skin test Corneometer MC 900. In the right foot, skin capacitance was 26·55 ± 4·14 arbitrary units (a.u.) at baseline, 28·90 ± 4·53 a.u. after 7 days of treatment and 32·05 ± 4·54 a.u. after 14 days of treatment. There was a significant increase in skin capacitance from baseline to 7 days of treatment (P < 0·001), from baseline to 14 treatment days (P < 0·001), as well as from 7 to 14 days of treatment (P < 0·001). The same significant (P < 0·001) increases were observed both in men and in women. No changes were noted in the left foot. At baseline, there was no difference in skin capacitance between right and left foot (P = 0·186). However, skin capacitance was significantly higher on the right versus left foot, both after 7 days (P < 0·001) and after 14 days of treatment (P < 0·001). In conclusion, results with the new foam appear encouraging in ameliorating skin dryness in the diabetic foot and further investigation is warranted.

Experimental xenoimplantation of antlerogenic cells into mandibular bone lesions in rabbits: two-year follow-up.

Different types of cells require activation, and take part in annual, dynamic growth of deer antlers. Stem cells play the most important role in this process. This report shows the results of a two-year long observation of xenogenic implant of antlerogenic stem cells (cell line MIC-1). The cells were derived from growing antler of a deer (Cervus elaphus), seeded onto Spongostan and placed in postoperative lesions of mandibular bones of 15 experimental rabbits. The healing process observed in the implantation sites in all rabbits was normal, and no local inflammatory response was ever observed. Histological and immunohistochemical evaluations were performed after 1, 2, 6, 12 and 24 months, and confirmed the participation of xenogenic cells in the regeneration processes, as well as a lack of rejection of the implants. The deficiencies in the bones were replaced by newly formed, thick fibrous bone tissue that underwent mineralization and was later remodelled into lamellar bone. The results of the experiment with rabbits allow us to believe that antlerogenic cells could be used in reconstruction of bone tissues in other species as well.

Gelatin-based haemostyptic Spongostan as a possible three-dimensional scaffold for a chondrocyte matrix?: an experimental study with bovine chondrocytes.

The gelatin-based haemostyptic compound Spongostan was tested as a three-dimensional (3D) chondrocyte matrix in an in vitro model for autologous chondrocyte transplantation using cells harvested from bovine knees. In a control experiment of monolayer cultures, the proliferation or de-differentiation of bovine chondrocytes was either not or only marginally influenced by the presence of Spongostan (0.3 mg/ml). In monolayers and 3-D Minusheet culture chambers, the cartilage-specific differentiation markers aggrecan and type-II collagen were ubiquitously present in a cell-associated fashion and in the pericellular matrix. The Minusheet cultures usually showed a markedly higher mRNA expression than monolayer cultures irrespective of whether Spongostan had been present or not during culture. Although the de-differentiation marker type-I collagen was also present, the ratio of type-I to type-II collagen or aggrecan to type-I collagen remained higher in Minusheet 3-D cultures than in monolayer cultures irrespective of whether Spongostan had been included in or excluded from the monolayer cultures. The concentration of GAG in Minusheet cultures reached its maximum after 14 days with a mean of 0.83 +/- 0.8 microg/10(6) cells; mean +/-, SEM, but remained considerably lower than in monolayer cultures with/without Spongostan. Our results suggest that Spongostan is in principle suitable as a 3-D chondrocyte matrix, as demonstrated in Minusheet chambers, in particular for a culture period of 14 days. Clinically, differentiating effects on chondrocytes, simple handling and optimal formability may render Spongostan an attractive 3-D scaffold for autologous chondrocyte transplantation.

Does sealing of the tract with absorbable gelatin (Spongostan) facilitate tubeless PCNL? A prospective study.

PURPOSE: To prospectively evaluate and study the role, relative safety, and efficacy of using absorbable gelatin tissue hemosealant (Spongostan) in patients selected for a gelatin-assisted "tubeless" percutaneous nephrolithotomy (PCNL); to study whether it facilitates and further reduces the morbidity vis-à-vis tubeless PCNL without gelatin; and to compare postoperative pain, analgesia requirement, hospital stay, return to work time, and other parameters in patients undergoing tubeless PCNL with gelatin and tubeless PCNL without the gelatin sealant. In addition, we briefly review various hemosealants used in tubeless PCNL by other workers. PATIENTS AND METHODS: Fifty selected previously qualified patients underwent tubeless PCNL. All procedures were performed by a single urologist (IS), and a resident administered random chit numbers and recorded pain scores and results of all the chosen parameters. Patients who fulfilled our criteria for tubeless PCNL were randomized to either the placement of a gelatin sealant or its omission. The data were analyzed with respect to several parameters. RESULTS: The mean age, stone burden, preoperative hemoglobin, blood urea, and serum creatinine values, hematocrit drop, and the time to return to work were not significantly different between the two groups. The hospital stay (P = 0.057), urinary extravasation (P < 0.001), and analgesia requirement (P < 0.001) were significantly lower in the patients who had undergone gelatin-sealant-assisted tubeless PCNL. CONCLUSIONS: Significantly less pain, lower analgesia requirement, and shorter hospital stay with lower wound soakage/discomfort were observed in the gelatin-assisted tubeless PCNL group v tubeless PCNL without gelatin packing. The use of absorbable gelatin sealant is safe, feasible, and a useful adjunct toward a safer tubeless PCNL in patients who previously qualified for tubeless PCNL.

High-pressure fibrin sealant foam: an effective hemostatic agent for treating severe parenchymal hemorrhage.

BACKGROUND: The majority of early trauma deaths are related to uncontrolled, noncompressible, parenchymal hemorrhage from truncal injuries. The purpose of this study was to formulate a fibrin sealant foam (FSF) able to control severe parenchymal bleeding without compression or vascular control. MATERIALS AND METHODS: FSF with high fibrinogen concentration (20 mg/mL) and low thrombin activity (5 U/mL) was prepared and pressurized by addition of liquid gas propellant. The efficacy of this foam was tested against a severe parenchymal hemorrhage, created by partial resection of liver lobes in anticoagulated rabbits (n = 7) and compared to untreated injury (n = 8) and placebo treatment (n = 7). The hemostatic efficacy of pressurized FSF (n = 8) was also compared to a commercially available liquid fibrin sealant (n = 8) and a developing dry powdered fibrin sealant product (n = 8) in the same model. RESULTS: The liver injury resulted in 122 +/- 11.5 mL blood loss and death of 75% of untreated rabbits (3.2-3.4 kg) within 1 h. Treatment with placebo foam had no effect on blood loss or mortality rate. Pressurized FSF significantly reduced bleeding, resulting in 56% (P < 0.05) and 66% (P < 0.01) reduction in blood loss as compared to untreated or placebo-treated animals, respectively, and 100% survival (P = 0.008). When pressurized FSF was compared with liquid and powdered forms of fibrin sealant, only foam significantly reduced blood loss (49%, P < 0.05) and mortality rate (54%, P < 0.05) of rabbits as compared to untreated control animals (n = 9). CONCLUSION: Biological nature, rapid preparation, coverage of large wound areas, and effective hemostatic properties make pressurized FSF an ideal candidate for treating nonoperable parenchymal injuries in damage control procedures.

The effects of fibrin sponge (Fibrinol), fibrin adhesive material (Tissucol), and epsilon-aminocaproic acid (Eaca) on the healing of experimental rat tibial lesions / Efeitos da esponja de fibrina (Fibrinol), adesivo fibrínico (Tissucol) e ácido épsilon-aminocapróico (EACA) no repara de defeitos ósseo em tíbia de rato

Foram estudados, histologicamente, os efeitos das associações Tissucol/Fibrinol e Tissucol/Fibrinol/EACA no reparo osseo. Cavidades cirúrgicas foram realizadas em ambas as tíbias de 25 ratos, de tal sorte que as tíbias direitas receberam duas cavidades e a esquerda, apenas uma. Os materiais testados foram colocados nas tíbias direitas, enquanto que as esquerdas serviram como controle. Em grupos de cinco, os animais foram sacrificados aos 1, 3, 7, 14 e 21 dias pós-operatórios. Os resultados obtidos mostram que: a) as associações Tissucol/Fibrinol e Tissucol/Fibrinol/EACA não interferiram na formação dos tecidos conjuntivo e ósseo; b) as associações Tissucol/Fibrinol e Tissucol/Fibrinol/EACA permitiram a neoformação óssea; c) resíduos de Tissucol/Fibrinol observados aos 21 dias pós-operatórios não impediram o reparo; d) no grupo Tissucol/Fibrinol/EACA, o material foi completamente absorvido e o reparo completou-se aos 21 dias pós-operatórios

Tissue reaction to three subcutaneously implanted local hemostatic agents.

Soft tissue response to three subcutaneously implanted local hemostatic agents; oxidised regenerated cellulose (Surgicel), gelatin sponge (Spongostan) and collagen sponge (Hemostagen) were evaluated histopathologically 7, 14, 21, 30 and 45 days following their implantation in rats. The results showed that all materials were well tolerated by soft tissues. These materials neither seemed to impair nor contribute to wound healing.

The influence of factor XIII on the fibrosing of a nerve anastomosis in the rat.

Although the fibrin adhesion enjoys increasing success in many areas of surgery, it has not become fully established in nerve anastomosis. It was in this area particularly that significant advantages were expected. As the fibrin clot dissolved prematurely, however, and dehiscences ensued, antifibrinolytic substances had to be added to the adhesive. Fibroses occurred frequently as a result, which to date encumber nerve adhesive. We examined Faktor XIII for his fibrosis-inducing effect because both presently available fibrin adhesives contain unphysiologically high concentrations of it. We were able to establish that Factor XIII possesses a fibrosis-promoting effect.