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Slow release of bone morphogenetic protein 2 from a gelatin sponge to promote regeneration of tracheal cartilage in a canine model.

OBJECTIVES: We investigated whether bone morphogenetic protein 2, released slowly from a gelatin sponge, could induce cartilage regeneration in a canine model of tracheomalacia and evaluated the long-term results. METHODS: A 1 x 5-cm gap was made in the anterior cervical trachea by removing 5-cm long strips of 10 sequential cartilagines. In the control group (n = 5), the gaps were left untreated. In the gelatin sponge group (n = 5), a gelatin sponge soaked in a buffer solution was implanted in each defect. In the bone morphogenetic protein group (n = 5), a gelatin sponge soaked in a buffer solution containing 12 microg bone morphogenetic protein 2 was implanted in each defect. RESULTS: Tracheomalacia was observed in the control and gelatin sponge groups but not in the bone morphogenetic protein group. No regenerated cartilage was detected in the control or gelatin sponge groups, even 6 months after surgery. In contrast, regenerated cartilage, which had developed from the host perichondrium, was observed around the stumps of the resected cartilagines in the bone morphogenetic protein group. This regenerated cartilage maintained the integrity of the internal lumen for longer than 6 months. A compressive fracture test revealed that the tracheal cartilage in the bone morphogenetic protein group was significantly more stable than that in the gelatin sponge and control groups (P =.0015 and P =.0001, respectively). CONCLUSIONS: In this canine model of tracheomalacia, cartilage regeneration was induced around the stumps of tracheal cartilagines by bone morphogenetic protein 2 released slowly from a gelatin sponge. This regenerated cartilage was not reabsorbed for longer than 6 months and was strong enough to maintain the integrity of the internal lumen of the trachea.

Animals↗

The use of hemostatic agents and sealants in urology.

PURPOSE: While hemostatic agents and sealants have long been used in the fields of surgery and urology, confusion persists about their indications for use and the optimal agent choice. We comprehensively defined and evaluated the scientific basis for hemostatic agent and sealant use in urology, and provide a conceptual framework for future research and discussion. MATERIALS AND METHODS: A MEDLINE search of all available literature concerning hemostatic agents in urology was performed, including topical hemostats, anti-fibrinolytics, fibrin sealants and matrix hemostats. Select references were also chosen from the broader surgical literature. Animal studies, case reports, retrospective and prospective studies, and opinion articles were reviewed. RESULTS: Hemostatic agents include a wide range of components. Recent literature has focused on fibrin sealants and matrix agents. Two main indications exist for hemostatic agents, including 1) hemostasis and 2) sealant. The best evidence for efficacy and safety exists for hemostasis, especially for nephrectomy and trauma. Newer data highlight urinary tract reconstruction, fistula and percutaneous tract closure, suture line strengthening and infertility as potential uses. Novel drug delivery and tissue engineering are areas with large clinical potential. CONCLUSIONS: Hemostatic agent use is promising and yet unproven for most conditions currently treated in urology. Hemostasis continues to be the main indication, which is well established. Few trials have examined comparative efficacy among hemostatic agents and further prospective studies are needed to justify additional indications as well as determine the optimal mode of use. Minimally invasive surgery will further drive the use of hemostatic agents and sealants. Cost-effective, evidence based hemostatic agent use will continue to challenge all urologists.

Anastomosis, Surgical↗

Involvement of reactive nitrogen oxides for acquisition of metastatic properties of benign tumors in a model of inflammation-based tumor progression.

The cells of a weakly tumorigenic and non-metastatic murine fibrosarcoma (QR-32) are converted into highly malignant tumors (acquiring metastatic potential) once they have grown in vivo after being co-implanted with gelatin sponge which induces inflammation. In the present study, we examined whether nitric oxide (NO) is involved in the inflammation-based tumor progression by administrating a specific inhibitor to inducible nitric oxide synthase, aminoguanidine (AG). First, we co-implanted 1 x 10(5) QR-32 cells with gelatin sponge (10 x 5 x 3 mm piece) into a subcutaneous space in C57BL6 mice. Administration of AG in drinking water (1%) had started 2 days before the tumor implantation and continued until the termination of the experiment. The incidence of tumor formation and the tumor growth did not differ between AG-treated group and -untreated group. On day 28, we excised the arising tumors to establish culture cell lines for evaluation of their acquisition of metastatic phenotype in other normal mice. Metastasis incidence and the number of metastatic colonies were significantly reduced in the tumor cell lines obtained from AG-treated mice compared to those from non-treated mice (p < 0.05). Immunohistochemical analysis demonstrated that inducible nitric oxide synthase and nitrotyrosine in the inflamed lesion were reduced in the AG-administered mice. However, intensity of 8-hydroxy-2-deoxyguanosine was not different between the groups. These results showed that nitric oxide and its reactive nitrogen oxide species cooperatively play a pivotal role in the progression of benign tumor cells in inflamed lesions.

Animals↗

Stem cell repair of physeal cartilage.

To evaluate the ability of cultured mesenchymal stem cells (MSC) to repair physeal defects, MSC-matrix constructs with 5% gelatin (group A), 10% gelatin/Gelfoam (Pharmacia, Peapack, NJ) (group B), and MSC grown in the presence of TGF-beta3 with Gelfoam (group C) were implanted in proximal tibial physeal defects created in 20 immature rabbits. Control groups (untreated partial defect and partial defect treated with Gelfoam) showed bony bar formation with varus deformities of 30 degrees and 28 degrees, respectively. Group A had an average 23 degrees varus deformity with bony bridge formation, and group B had mild varus angulation (average 14 degrees) of the proximal tibia. In group C, there was no significant varus deformity (average 9 degrees), and histologic examination showed that some of the columnation areas interspersed with chondrocytes were irregularly arranged in the matrix. These findings suggest that repair of physeal defects can be enhanced by the implantation of MSC cultured with TGF-beta3.

Animals↗

Direct round window application of gentamicin with varying delivery vehicles: a comparison of ototoxicity.

OBJECTIVE: To evaluate patterns of ototoxic damage sustained from gentamicin applied directly to the round window in varying delivery vehicles. SETTING: The search for a reliable method of drug delivery to the inner ear continues. Vehicles such as Gelfoam, hyaluronic acid, and fibrin may allow for a more reproducible pattern of ototoxic damage. STUDY DESIGN: Histological evaluation of vestibular and cochlear damage was performed on Mongolian gerbils after a known dosage of gentamicin in different delivery vehicles. RESULTS: Variable ototoxic damage was caused by Gelfoam and fibrin-based vehicles. No ototoxic damage was found in the Healon vehicle. The vehicle of fibrin and Gelfoam combined resulted in severe damage. There was no evidence of selective cochlear or vestibular ototoxicity in any of the vehicles tested. CONCLUSIONS AND SIGNIFICANCE: The fibrin/Gelfoam vehicle was the only delivery system to produce reliable damage. Ototoxic damage depended on the vehicle. We found no evidence for selective vestibular ototoxicity with gentamicin.

Administration, Topical↗

Prospective, randomized, controlled clinical trial of a novel matrix hemostatic sealant in children undergoing adenoidectomy.

PROBLEM ADDRESSED: Floseal is a novel matrix hemostatic sealant composed of collagen-derived particles and topical bovine-derived thrombin. It is applied as a high-viscosity gel for hemostasis and has been clinically proven to control bleeding. This study is a prospective, randomized, controlled clinical trial of Floseal sealant compared to traditional suction cautery hemostasis in children undergoing adenoidectomy. METHODS AND MEASURES: Seventy patients (mean age 7.0 yrs, 45.7% male) with obstructive sleep apnea underwent traditional cold steel adenoidectomy with an adenoid curette and were then randomized to receive the hemostatic sealant (Floseal) or cautery to obtain hemostasis. Patients were crossed over to the other hemostatic technique if hemostasis was not achieved after more than 100 mL of blood loss or 15 minutes elapsed time. Objective data collected included time to hemostasis and blood loss during hemostasis. Visual analog scales (VAS) were used to record subjective data by the operating surgeon including bleeding following adenoid pack removal (0 = none, 3 = brisk) and ease of operation (1 = extremely easy, 6 = extremely difficult). Parents recorded diet on a journal and were contacted by phone at postoperative day 7 and questioned with regard to return to regular diet and use of narcotics. RESULTS: Compared to patients in the cautery group (n = 35), Floseal patients (n = 35) had significantly shorter times to hemostasis (0.6 +/- 1.3 minutes vs 9.5 +/- 5.4 minutes [mean +/- SD], P < 0.001), less blood loss (2.5 +/- 9.2 mL vs 29.4 +/- 27.1 mL, P < 0.001), less subjective bleeding (0.0 +/- 0.6 vs 2.0 +/- 0.7, [median 4-point VAS +/- SD], P < 0.001), and subjectively easier operations (2.6 +/- 1.0 vs 5.2 +/- 1.0 [mean 6-point VAS +/- SD], P < 0.001). Furthermore, Floseal patients returned to regular diet earlier (2.7 +/- 0.7 vs 4.1 +/- 0.5 days [mean +/- SD], P < 0.001) and had less use of narcotics at 7 days postoperatively (40% vs 69%, P < 0.05). Lastly, three patients in the cautery group were crossed over to the Floseal group, but no Floseal subjects were crossed over to the cautery group. The retail cost of Floseal is US 85 dollars. Operating room costs are estimated at US 12 dollars/minute. Reducing the operative length by 8.9 minutes on average produces a cost savings of US 106.80 dollars per operation. There were no complications in either experimental group including postoperative hemorrhage, hospitalization, blood transfusion, or aspiration. CONCLUSIONS: Floseal matrix hemostatic sealant is a safe, efficacious, easy, and cost-effective technique for obtaining hemostasis in children undergoing adenoidectomy. Limitations of the study include the fact that it is nonblinded, which does allow for some bias in the subjective data recorded. However, utilizing 4 different operating surgeons, 3 of whom were not affiliated with the study, minimized this. CLINICAL SIGNIFICANCE OF STUDY: This study demonstrates the safety and efficacy of a novel hemostatic sealant in children undergoing adenoidectomy. Floseal matrix hemostatic sealant can be used as a first-line hemostatic agent, and it is a good tool in the armamentarium of otolaryngologists who encounter significant bleeding following adenoidectomy.

Adenoidectomy↗

Split-thickness skin grafting in postmastoidectomy revision and in lateral temporal bone resection.

OBJECTIVES: Use of split-thickness skin grafts (STSG) in revision canal wall-down (CWD) mastoidectomy was compared with STSG in lateral temporal bone resection (LTBR). STUDY DESIGN AND SETTING: A retrospective study of 11 patients undergoing revision CWD mastoidectomy and 6 patients undergoing LTBR with STSG in an academic health center setting. RESULTS: Successful epithelialization of the mastoid cavity occurred in 9 patients (82%) undergoing CWD mastoidectomy. Subjective success, measured as reduction in complaints of otorrhea, occurred in 10 patients (91%). In the 6 patients who underwent LTBR and STSG successful epithelialization of the temporal bone defect occurred in 5 patients (83%). CONCLUSIONS: Successful and rapid epithelialization occurred in the revision mastoidectomy cohort as well as in the primary temporal bone resection cohort. SIGNIFICANCE: Placement of STSG is a useful adjunct in revision CWD mastoidectomy as well as in primary LTBR for cancer.

Adult↗

Crosslinked hydrogels for tympanic membrane repair.

PROBLEM: To provide a less expensive and more convenient protocol for the treatment of tympanic membrane perforations (TMPs). METHODS: Several materials were prepared and compared for TMP repair including Carbylan-SX, Gelatin-DTPH-PEGDA (GX), Carbylan-S/Gelatin-DTPH (Carbylan-GSX) (injectable and sponge), Gelfoam, Epifilm, and crosslinked thiolated chondroitin sulfate (CS-DTPH-PEGDA [CS-SX]). Hartley pigmented guinea pigs (Elm Hill) underwent bilateral myringotomy with 1 ear left as a control and the other treated with one of the previously mentioned materials. RESULTS: Carbylan-GSX (injectable and sponge), Gelfoam with saline, and CS-SX had the shortest time for TMP closure. Epifilm, Carbylan, and gelatin preparations resulted in closure rates similar to controls. CS-SX showed a marked inflammatory reaction compared with controls and other materials based on neutrophil, lymphocyte, epitheloid counts, and degree of fibrosis. CONCLUSIONS: This study shows the validity of Carbylan-GSX compared with Gelfoam as a material to promote TMP closure in an acute TMP guinea pig model.

Animals↗

[3D cellular models: a powerful access to cutaneous physiology and to innovative developments of cosmetic active compounds].

Two different anti-ageing cosmetic actives based respectively, on dermal compartment regeneration and on dermoepidermal reinforcement, have been developed using tissular engineering models. Conjointly use of different innovative three-dimensional models such as reconstructed dermis and skin built with human cells coming from variable aged donors allowed first, a better understanding of matrix modifications due to ageing and second, the screening of active ingredients highly targeted to reverse observed damages. The validity of such three-dimensional models has been then confirmed by in vivo studies on healthy volunteers.

Adult↗

Evaluation of hyaluronic acid sheet for the prevention of postlaminectomy adhesions.

BACKGROUND CONTEXT: Various materials have been tested for their ability to maintain a barrier between muscles and epidural space in order to physically or chemically inhibit scar ingrowths. Hyaluronic acid (HA) solution and gel have been reported to be effective in preventing adhesions postlaminectomy; however, neither has been used clinically after spinal surgery. PURPOSE: To determine the efficacy of HA sheet for the prevention of postlaminectomy adhesions compared with that of HA gel or another sheet. STUDY DESIGN/SETTING: An animal model of lumbar laminectomy in rabbits was used to study postoperative scar tissue formation around the spinal cord. The histologic effects of HA sheet were compared with those of Gelfoam (GF) and further evaluated by an inflammation model using rhTNF-alpha. PATIENT SAMPLE: Rabbit. OUTCOME MEASURES: Histologic examination. METHODS: Five rabbits were killed at 2, 4, 8, and 24 weeks after laminectomy, respectively. Another 18 rabbits were examined in an environment of active inflammation experimentally induced by rhTNF-alpha to compare the effects of HA sheet with those of GF or HA gel. Histologic examination was performed to quantitatively assess invasive scar formation or inflammation postlaminectomy, and then, the histologic effects of HA sheet were compared with those of GF or HA gel. RESULTS: In the HA group, significantly, the area of subarachnoid space was larger, distance from the surface of dura to scar tissues was greater, the number of inflammatory cells in the scar tissues at the site of laminectomy was less, and enlargement of dura was suppressed. Using an inflammation model, we also demonstrated the efficacy of HA sheet treatment. CONCLUSIONS: In an experimental laminectomy model, HA sheet formed a solid interpositional membrane barrier and exhibited anti-inflammatory activity. Further investigations will be needed for HA sheet to be used clinically.

Animals↗

An in vitro and in vivo analysis of fibrin glue use to control bone morphogenetic protein diffusion and bone morphogenetic protein-stimulated bone growth.

BACKGROUND CONTEXT: Recombinant human bone morphogenetic protein-2 (rh-BMP2) has become popular for augmenting spine fusion in the lumbar and cervical spine. Concerns exist, however, over bone morphogenetic protein (BMP)-stimulated soft-tissue swelling and bone growth stimulation in areas where bone is not desired, especially as the material "leaks" into such spaces. The most detrimental effects of such leakage might be airway compromise, while heterotopic bone formation into the spinal canal has been reported in animal and human studies. Fibrin glue has been used as a carrier of many osteoinductive materials; however, its efficacy at modulating the clinical effects of BMP are not known. The amorphous nature of fibrin glue makes it a candidate to control diffusion of BMP and possibly limit bone formation by limiting BMP diffusion to areas where such bone is not desired. PURPOSE: To evaluate the use of fibrin glue to limit BMP diffusion and BMP-stimulated bone growth. STUDY DESIGN/SETTING: This is an in vitro basic science study and an in vivo prospective randomized animal study. STUDY SAMPLE: Eighteen Lewis rats. OUTCOME MEASURES: In vitro study: Enzyme-linked immunosorbent assay measurement of rh-BMP2 concentration in saline. In vivo study: At day 60, rats were evaluated for neurologic deficits before sacrifice. Spines were harvested, and the following studies were performed: 1) manual testing for fusion and bone growth; 2) X-ray evaluation; 3) Micro-computed tomography (micro-CT) scans. METHODS: In vitro study: Collagen sponges soaked with BMP at two different concentrations were incubated in saline solution with and without encapsulation by fibrin glue. Saline BMP concentrations were measured at consecutive time points. In vivo study: A rat fusion model using rh-BMP2 for fusion has been developed and tested with resultant100% fusion in over 100 rats. Lewis rats were divided into two groups and treated as follows: I: Exposure of L4-L5 transverse processes, decortication, and placement of BMP sponge in the lateral intertransverse space. II: Exposure and decortication as above and placement of fibrin glue before BMP sponge placement. RESULTS: In vitro study: Peak rh-BMP2 concentrations in saline were 20% and 45% of the maximum possible for fibrin glue encapsulated sponges and controls, respectively, with a more gradual increase to peak concentration in samples encapsulated in fibrin glue. In vivo study: No rats exhibited any neurologic deficits. X-rays revealed at least partial bone formation in all rats. Manual testing of intertransverse fusion spines revealed 100% fusion in rats treated with BMP only, whereas rats treated with fibrin glue before placement of BMP sponges revealed only one possible fusion. Posterior-lateral bone formation was present on X-ray in both groups, and micro-CT imaging revealed bridging bone from transverse processes to the BMP-stimulated bone in the control groups. In spines treated with fibrin glue before rh-BMP2 placement, bone formation could still be seen within the soft tissues; however, bridging bone connecting to the transverse processes was either significantly decreased or not present. CONCLUSIONS: Fibrin glue can limit rh-BMP2 diffusion. Also, because it limited bone formation at the transverse processes, it can be inferred that fibrin glue can limit bone formation when used to separate areas of desired bone formation from areas where bone formation is not desired.

Animals↗

An alternative approach to maxillofacial arteriovenous malformations with transosseous direct puncture embolization.

The management of arteriovenous (AVM) malformations of the jaws is complex and requires an integrated team approach. Subspecialists, such as maxillofacial surgeons, interventional radiologists, and critical care intensivists, are commonly involved in the management of these patients. The current treatment options for maxillofacial AVMs are surgical resection combined with endovascular embolization. Surgical treatment of arteriovenous malformations has been associated with significant morbidity and mortality due to potential for massive blood loss. In the pediatric population extensive resection of the craniofacial skeleton may be associated with growth disturbance, functional compromise, and cosmetic deformity. We report a novel technique using endovascular embolization via direct transosseous puncture for a high-flow vascular malformation, obviating the need for extensive surgical resection, and review the important clinical aspects of these life-threatening lesions.

Arteriovenous Malformations↗

Improved hemostasis during laparoscopic partial nephrectomy using gelatin matrix thrombin sealant.

OBJECTIVES: To evaluate whether using a biologic hemostatic sealant facilitates hemostasis during laparoscopic partial nephrectomy. Secure and durable parenchymal hemostasis is a critical requirement during laparoscopic partial nephrectomy. METHODS: Since September 1999, laparoscopic partial nephrectomy has been performed in more than 300 patients by a single surgeon, duplicating open surgical principles. Recently, from patient 225 onward, we modified our technique by incorporating topical application of a gelatin matrix thrombin sealant (FloSeal) to cover the partial nephrectomy bed before sutured renorrhaphy over a Surgicel bolster. The impact of FloSeal on reducing hemorrhagic complications was evaluated by comparing two sequential groups of patients: group 1 consisted of 68 patients in whom FloSeal was not used (patients 156 to 224) and group 2 consisted of 63 patients in whom it was used (patients 225 to 288). RESULTS: Groups 1 (no FloSeal) and 2 (FloSeal) were comparable in tumor size, number of central tumors, and performance of pelvicaliceal suture repair (84% versus 92%; P = 0.16). Intraoperative variables were also comparable in terms of mean warm ischemia time (36.1 versus 37.2 minutes; P = 0.55), blood loss (150 versus 106 mL; P = 0.36), operative time, and hospital stay. However, the FloSeal group had significantly fewer overall complications (37% versus 16%; P = 0.008) and tended toward a lower rate of hemorrhagic complications (12% versus 3%), although this did not achieve statistical significance (P = 0.08). CONCLUSIONS: The results of this study have shown that adjunctive use of gelatin matrix thrombin sealant substantially enhances parenchymal hemostasis and has decreased our procedural and hemorrhagic complications to levels comparable with contemporary open partial nephrectomy series. This gelatin matrix-thrombin tissue sealant is now a routine part of laparoscopic partial nephrectomy at our institution.

Gelatin Sponge, Absorbable↗

Placenta percreta: balloon occlusion and embolization of the internal iliac arteries to reduce intraoperative blood losses.

Obstetric hemorrhage is still a potential cause of maternal mortality and morbidity. Angiographic embolization techniques have been described in cases of postcesarean bleeding, vaginal wall hematomas, cervical ectopic pregnancies, and postpartum bleeding to control persistent bleeding from pelvic vessels. We describe two cases of pregnancy complicated with placenta percreta. Balloon occlusion and embolization of the hypogastric arteries were performed during the cesarean section and hysterectomy, resulting in a remarkable reduction in intraoperative blood loss. Balloon occlusion and embolization of the internal iliac arteries significantly reduce intraoperative blood losses.

Adult↗

Gelatin sponge plug to seal fetoscopy port sites: technique in ovine and primate models.

Amniotic fluid leakage and rupture of membranes are common complications of fetoscopy. We describe a plug technique for leakproof removal of endoscopic cannulas. Thirty gelatin sponge plugs were introduced in 5 pregnant ewes and 5 pregnant rhesus monkeys. In the primate model no evidence of amniorrhexis was noted on postoperative ultrasonography. Myometrium and membranes at the port sites were intact at term. A gelatin sponge plug technique may facilitate leakproof port removal after fetoscopy.

Amniotic Fluid↗

Preventing symblepharon formation with a gelatin sponge in the eye of a patient with an alkali burn.

PURPOSE: To report a patient with symblepharon caused by an alkali injury whom we treated by using a gelatin sponge. METHODS: Four days after the burn, a gelatin sponge was inserted into the upper conjunctival sac to separate the raw conjunctival surfaces. RESULTS: The gelatin sponge adhered to the tarsal side of the upper fornix and was kept there for 11 days until no epithelial defect was visible in the bulbar conjunctiva. No symblepharon formation was observed 6 months after the injury. CONCLUSION: Application of a gelatin sponge proved to be a simple and effective way of preventing symblepharon formation after an alkali burn.

Alkalies↗