Bone formation with a biphasic calcium phosphate combined with fibrin sealant in maxillary sinus floor elevation for delayed dental implant.

OBJECTIVES: The aim of this study was to evaluate the extent and quality of new bone 6 months after sinus lift with biphasic micro- and macroporous calcium phosphate combined with fibrin sealant (MBCP-FS) and the 1-year implant success rate in the augmented site. MATERIAL AND METHODS: MBCP-FS was applied to one sinus in 96 subjects requiring augmentation for delayed dental implant placement. In subjects who required bilateral lifts (N = 33), the MBCP-FS sinus was randomly selected; the contralateral sinus was grafted with autologous bone (mixed with Bio-Oss when harvested bone volume was insufficient. Panoramic views were taken periodically prior to and up to 18 months post-lift. Histomorphometric analysis was conducted on biopsies taken during implant placement 6 months after augmentation. Implant functionality and prosthesis success were assessed clinically 1 year after implant placement. RESULTS: In MBCP-FS sinuses, 20.6 ± 8.5% new, mainly lamellar bone was observed. Implants were placed as planned in 78/85 evaluable subjects (91.8%) 6 months after sinus lift. Graft heights remained stable 1 year after placement; 94.7% (142/150) of implants were functional. The amount and quality of new bone and implant success rates with MBCP-FS were similar to autologous bone graft (mixed with Bio-Oss in 30/31 evaluable subjects). MBCP-FS was safe and well-tolerated. CONCLUSIONS: MBCP-FS is safe and effective in sinus floor elevation for dental implant placement, supporting bone regeneration and with high 1-year implant success rates similar to autologous bone mixed with Bio-Oss.

Use of fibrin sealant as a hemostatic agent in expanded polytetrafluoroethylene graft placement surgery.

BACKGROUND: The low thrombogenicity, porosity, and limited elasticity of expanded polytetrafluoroethylene (ePTFE) vascular grafts, although beneficial, may exacerbate the problem of suture-line bleeding at vascular anastomoses and consequently lead to increased operating times. The overall objective of this prospective, randomized, controlled, subject-blinded, multicenter phase 2 study was to evaluate the efficacy and safety of a fibrin sealant containing 500 IU/mL thrombin and synthetic aprotinin (FS; marketed in the United States under the name TISSEEL) for hemostasis in subjects undergoing vascular surgery and receiving prosthetic ePTFE vascular grafts. METHODS: FS was compared with manual compression with surgical gauze pads, a standard of care for hemostasis in vascular surgery. Two FS polymerization/setting times (60 and 120 seconds) were investigated to evaluate influence on the efficacy results. Patients undergoing ePTFE graft placement surgery (N = 73) who experienced bleeding that required treatment after surgical hemostasis were randomized to be treated with FS with clamps opened at 60 seconds (FS-60; N = 26), with FS with clamps opened at 120 seconds (FS-120; N = 24), or with manual compression with surgical gauze pads (control; N = 23). The proportion of subjects achieving hemostasis at 4 minutes (primary endpoint) as well as at 6 and 10 minutes (secondary endpoints) in the three treatment groups was analyzed using logistic regression analysis, taking into account gender, age, type of intervention, severity of bleeding, systolic blood pressure, diastolic blood pressure, heparin coating of the ePTFE graft, and platelet inhibitors. RESULTS: There were substantial differences in the proportion of subjects who achieved hemostasis at the study suture line at 4 minutes from treatment application between FS-120 (62.5%) and control (34.8%) groups (a 79.6% relative improvement). Logistic regression analyses found a statistically significant treatment effect at the 10% level in the odds ratio (OR) of achieving hemostasis at 4 minutes between the FS-120 and control groups (OR = 3.98, p = 0.0991). Furthermore, it has been shown that the perioperative administration of platelet inhibitors significantly influences (OR = 3.89, p = 0.0607) hemostasis rates at the primary endpoint. No statistically significant treatment effects were found for the other factors. Logistic regression analyses performed on the secondary endpoints demonstrated a significant treatment effect of achieving hemostasis at 6 minutes (OR = 9.92, p = 0.0225) and at 10 minutes (OR = 6.70, p = 0.0708) between the FS-120 and control groups. Statistically significant effects in the logistic regression analyses were found at the 10% level in the OR of achieving hemostasis at 6 and 10 minutes, respectively, for the following factors: FS-120 versus control group (OR = 9.92; p = 0.0225 and OR = 6.70; p = 0.0708, respectively), type of intervention (OR = 0.3; p = 0.0775 and OR = 0.25; p = 0.0402, respectively), and heparin coating of the ePTFE prosthesis (OR = 4.83; p = 0.0413 and OR = 3.65; p = 0.0911, respectively). FS was safe and well-tolerated, as indicated by the lack of any related serious adverse events. CONCLUSION: The findings from this phase 2 study support the strong safety profile of FS and suggest that it is an efficacious hemostatic agent in ePTFE graft placement surgery, as well as a useful tool in peripheral vascular surgery applications.

Efficacy and safety of a fibrin sealant for adherence of autologous skin grafts to burn wounds: results of a phase 3 clinical study.

The objective of this phase 3, multicentered, prospective, randomized, evaluator-blinded, clinical study was to compare skin graft adherence utilizing a fibrin sealant containing 4 IU/ml thrombin (FS 4IU VH S/D [FS 4IU VH S/D will be marketed under the trade name ARTISS upon licensure in the United States]) to graft adherence utilizing staples in burn patients requiring wound excision and skin grafting. FS 4IU VH S/D was compared with staples in 138 patients. Patients had burn wounds measuring < or =40% of total body surface area with two comparable test sites measuring between 1 and 4% total body surface area each. Wound closure at day 28 was assessed using test site planimetry and review of day 28 photographs by three independent blinded evaluators (primary endpoint analysis). Secondary efficacy measures included hematoma/seroma on day 1, engraftment on day 5, and wound closure on day 14. Investigator and patient-reported outcomes were also assessed. The proportion of test sites with complete wound closure at day 28 was 70.3% in FS 4IU VH S/D treated sites and 65.8% in stapled sites, as assessed by planimetry. Blinded review of day 28 photographs confirmed that the rate of complete wound closure was similar between the two treatments, although the overall assessed rates of closure were lower than those determined by planimetry: FS 4IU VH S/D (43.3%) and staples (37.0%). The lower limit of the 97.5% confidence interval of the difference between FS 4IU VH S/D and staples was -0.029, which is above the predefined noninferiority margin of -0.1. Therefore, FS 4IU VH S/D is at least as efficacious as staples at the 97.5% one-sided level for complete wound closure by day 28. Hematoma/seroma on day 1 occurred at significantly (P < .0001) fewer FS 4IU VH S/D-treated sites (29.7% [95% CI 22.2-38.1%]) compared with stapled sites (62.3% [95% CI 53.7-70.4%]). Engraftment on day 5 was deemed to be 100% in 62.3% (95% CI 53.7-70.4%) of the FS 4IU VH S/D-treated sites and 55.1% (95% CI 46.4-63.5%) of the stapled sites (P = .0890). Complete wound closure by day 14 occurred in 48.8% (95% CI 39.9-57.8%) of the FS 4IU VH S/D treated sites and 42.6% (95% CI 34.0-51.6%) of the stapled sites (P = .2299). FS 4IU VH S/D scored significantly better than staples for all investigator-assessed outcomes, namely quality of graft adherence (P < .0001), preference for method of fixation (P < .0001), satisfaction with graft fixation (P < .0001), and overall quality of healing (P < .0001). Likewise, FS 4IU VH S/D scored significantly better than staples for all patient-assessed outcomes, namely anxiety about pain (P < .0001) and treatment preference (P <.0001). The safety profile of FS 4IU VH S/D was excellent as indicated by the lack of any related serious adverse experiences. These findings demonstrate that FS 4IU VH S/D is safe and effective for attachment of skin grafts, with outcomes at least as good as or better than staple fixation.

Comparison of fibrin sealant and staples for attaching split-thickness autologous sheet grafts in patients with deep partial- or full-thickness burn wounds: a phase 1/2 clinical study.

We undertook a multicenter, randomized, controlled, phase 1/2 clinical study to investigate the safety and efficacy of a fibrin sealant containing 4 IU/ml thrombin (FS 4IU) for the attachment of autologous sheet grafts in patients with deep partial-thickness or full-thickness burn wounds. Fibrin sealant (FS 4IU) was compared with staples for adherence of sheet grafts in 40 patients. Patients had to have burn wounds measuring 40% TBSA or less with two comparable test sites measuring between 1% and 4% TBSA each. Wound beds were prepared before treatment assignment, which was randomized. Percent area of hematoma/seroma at Day 1 (P = .0138) and questionable viability at Day 5 (P = .0182) were significantly less for FS 4IU-treated sites. Median percent area of graft survival on Day 14 was 100% for both treatments (P = .3525). The percentage of completely closed sites generally was greater for FS 4IU-sites on Days 5 to 91; the maximum difference occurred at Day 28 (79.5% vs 59%; P = .0215). The safety profile of FS 4IU was excellent as indicated by the lack of any related serious adverse experiences. These findings indicate that FS 4IU is safe and effective for fixation of skin grafts, with outcomes similar to or better than staple fixation. The data suggest that FS 4IU is a promising candidate for further clinical studies focusing on skin graft adhesion and burn wound healing.