Search

Fibrin sealants are well-established components of the surgical toolbox, especially in procedures that harbor a high risk of perioperative bleeding. Their widespread use as hemostats, sealants or tissue-adhesives in various surgical settings has shown that the choice of the appropriate sealant system affects the clinical outcome. While many studies have compared the hemostatic efficiency of fibrin sealants to that of other natural or synthetic sealants, there is still limited data on how subtle differences in fibrin sealant formulations relate to their biological performance. Here, we performed an in-depth physicochemical and biological characterization of the two most commonly used fibrin sealants in the US and Europe: TISSEEL™ ("FS") and VISTASEAL™/VERASEAL™ ("FS+Osm"). Our chemical analyses demonstrated differences between the two sealants, with lower fibrinogen concentrations and supraphysiological osmolality in the FS+Osm formulation. Rheological testing revealed FS clots have greater clot stiffness, which strongly correlated with network density. Ultrastructural analysis by scanning electron microscopy revealed differences between FS and FS+Osm fibrin networks, the latter characterized by a largely amorphous hydrogel structure in contrast to the physiological fibrillar network of FS. Cytocompatibility experiments with human fibroblasts seeded on FS and FS+Osm fibrin networks, or cultured in presence of sealant extracts, revealed that FS+Osm induced apoptosis, which was not observed with FS. Although differential sealant osmolality and amounts of fibrinogen, as well as the presence of Factor XIII or additives such as antifibrinolytics, may explain the mechanical and structural differences observed between the two fibrin sealants, none of these substances are known to cause apoptosis at the respective concentrations in the sealant formulation. We thus conclude that hyper osmolality in the FS+Osm formulation is the primary trigger of apoptosis-a mechanism that should be evaluated in more detail, as it may affect the cellular wound healing response in situ., (© 2022 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Purpose: Topical hemostatic agents can be classified as active or passive. This study compared the hemostatic efficacy of an active agent, recombinant thrombin (RECOTHROM ® [rT]) plus gelatin sponge carrier versus a passive agent, oxidized regenerated cellulose (TABOTAMP ® /SURGICEL ® [ORC]), in a porcine liver abrasion model., Materials and Methods: Eight pigs were used, four of them were heparinized. A total of 80 liver lesions were created, 40 of them in heparinized pigs. Lesions were treated with rT plus gelatin sponge or ORC. Bleeding rate was quantified before treatment by applying pre-weighed gauze. Time to hemostasis was assessed visually for 10 minutes., Results: Seven of the 80 lesions were excluded for having initial bleeding rates exceeding the target of 10 g/min. Sixteen and 20 lesions were treated with rT plus gelatin sponge and 19 and 18 lesions were treated with ORC, in non-heparinized and heparinized animals, respectively. Time to hemostasis (median [IQR]) was significantly shorter with rT plus gelatin sponge (30 [30,30] seconds) in heparinized and non-heparinized animals versus ORC in non-heparinized (180 [120,210] seconds) and heparinized animals (215 [135,345] seconds); P  < 0.0001 for both comparisons. In heparinized animals, ORC took longer to achieve hemostasis, with treatment failure in 2/18 lesions. Time to hemostasis with ORC was longer for lesions in heparinized animals with initial bleeding rates of >5-10 g/min (285 [225,394] seconds) versus ≤5 g/min (175 [108,290] seconds)., Conclusions: In this model, rT plus gelatin sponge carrier (active) was a more effective hemostat than ORC (passive) in both heparinized and non-heparinized animals.

Purpose: Management of bleeding during surgery can be aided by the application of topical hemostatic agents. This study compared the hemostatic efficacy of a new powder agent containing collagen, chondroitin sulfate, and thrombin (PCCT) with a flowable gelatin-thrombin matrix with smooth particles (SmGM) in a porcine liver bleeding model. Materials and Methods: Lesions 4-6 mm deep and ∼10 mm in diameter were created in porcine livers and treated with either SmGM or PCCT. Bleeding rate and grade were quantified before and 3, 7, and 11 minutes after treatment. Results: Thirty-two lesions each were treated with SmGM or PCCT; the median (Q1, Q3) initial bleeding rate was comparable between the two groups (8.43 [6.18, 10.68] g/min and 7.15 [5.16, 9.63] g/min, respectively). The residual bleeding rate was significantly lower at all time-points post treatment for SmGM compared with PCCT (3 minutes: 0.14 [0.07, 0.21] versus 0.46 [0.20, 1.20] g/min, p  < 0.0001; 7 minutes: 0.07 [0.04, 0.11] versus 0.12 [0.08, 0.39] g/min, p  = 0.001; 11 minutes: 0.05 [0.03, 0.08] versus 0.07 [0.05, 0.12] g/min, p  = 0.043). Bleeding grade at 3 minutes was also significantly lower for SmGM compared with PCCT (median [Q1, Q3] 0.0 [0.0, 0.0] versus 1.0 [1.0, 2.0], p  < 0.0001). PCCT required reapplication in approximately one-third of applications due to insufficient hemostasis 4 minutes after initial application and showed a tendency to stick to the wet gauze during approximation. Conclusions: In this bleeding model, treatment with SmGM resulted in reduced blood loss, no need for reapplication and was easier to apply compared with PCCT.

Two self-adhering hemostatic patches, based on either PEG-coated collagen (PCC) or PEG-coated oxidized cellulose (PCOC), are compared regarding to maximum burst pressure, mechanical stability, and swelling. In addition, the induction of tissue adhesions by the materials was assessed in a rabbit liver abrasion model. Both materials showed comparable sealing efficacy in a burst pressure test (37 ± 16 vs. 35 ± 8 mmHg, P = 0.730). After incubation in human plasma, PCC retained its mechanical properties over the test period of 8 h, while PCOC showed faster degradation after the 2 h time-point. The degradation led to a significantly decreased force at break (minimum force at break 0.55 N during 8 h for PCC, 0.27 N for PCOC; p < 0.001). Further, PCC allowed significantly higher deformation before break (52% after 4 h and 50% after 8 h for PCC, 18% after 4 h and 23% after 8 h for PCOC; p = 0.003 and p < 0.001 for 4 h and 8 h, respectively) and showed less swelling in human plasma (maximum increase in thickness: ~20% PCC, ~100% PCOC). Faster degradation of PCOC was visible macroscopically and histologically in vivo after 14 days. PCC showed visible structural residues with little cellular infiltration while strong infiltration with no remaining structural material was seen with PCOC. In vivo, a higher incidence of adhesion formation after PCOC application was detected. In conclusion, PCC has more reliable mechanical properties, reduced swelling, and less adhesion formation than PCOC. PCC may offer greater clinical benefit for surgeons in procedures that have potential risk for body fluid leakage or that require prolonged mechanical stability.

Trends in the development of hemostatic agents are towards self-adhering pads. This study investigates a novel biomaterial made of a polyethylene glycol-coated collagen pad (PCC). The swelling and adherence of PCC were investigated in vitro, and the hemostatic and sealing ability was investigated in vivo. In vitro, the maximum swell of PCC submerged in human plasma for 24 h is 65%. The greatest swell was in thickness, averaging 24% to a mean thickness of 2.5 ± 0.19 mm (mean±SD) (N = 20). PCC withstood clinically relevant pressures when applied to a collagen casing washed with bile, lymph, urine, saline, and cerebrospinal fluid mixed at 33% and 67% with blood. In vivo, PCC provided complete hemostasis when applied to severe, arterial bleeds of actively ventilated pulmonary parenchyma at 3, 5, 8, and 10 min after application in a heparinized porcine pulmonary segmentectomy model. The mean rate of bleeding was 17.7 ± 8.6 ml/min. The lungs were ventilated at 15 ± 4 breaths per min and an airway pressure of 19 ± 2 cm H2O. PCC had no incidence of hematoma and an 11% incidence of intraoperative air leak (N = 36). These data are promising for future clinical application of a new versatile, self-adhering hemostatic sealing pad consisting of a polyethylene glycol-coated collagen., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)