The Use of Self-Assembling Peptides (PuraStat™) in Functional Endoscopic Sinus Surgery for Haemostasis and Reducing Adhesion Formation. A Case Series of 94 Patients.

INTRODUCTION: Functional endoscopic sinus surgery (FESS) is a treatment option for patients with chronic rhinosinusitis. Bleeding and adhesions are common complications postoperatively. OBJECTIVE: To assess the effectiveness of PuraStat™ (3-D Matrix Medical Technology Pty Ltd, Melbourne, Australia) for use in FESS to achieve haemostasis and reduce adhesion formation. MATERIALS AND METHODS: A retrospective chart review over four years was performed on 94 patients undergoing FESS by a single surgeon, using PuraStat™ in absence of nasal packing. RESULTS: Twenty-eight patients underwent complete FESS and 66 cases limited FESS most often combined with nasal surgery. Six patients had bleeding postoperatively, of which only four required additional treatment (4.25%). Twenty-three patients (24.47%) required debridement during the follow up, simply performed by suction for 13 or by scissors for 10. No patient required revision surgery for adhesion. CONCLUSION: PuraStat™ used for the first time in context of FESS seems to be effective in achieving haemostasis, reducing adhesion formation, and avoiding nasal packing in most patients.

Clinical Use of the Self-Assembling Peptide RADA16: A Review of Current and Future Trends in Biomedicine.

RADA16 is a synthetic peptide that exists as a viscous solution in an acidic formulation. In an acidic aqueous environment, the peptides spontaneously self-assemble into ß-sheet nanofibers. Upon exposure and buffering of RADA16 solution to the physiological pH of biological fluids such as blood, interstitial fluid and lymph, the nanofibers begin physically crosslinking within seconds into a stable interwoven transparent hydrogel 3-D matrix. The RADA16 nanofiber hydrogel structure closely resembles the 3-dimensional architecture of native extracellular matrices. These properties make RADA16 formulations ideal topical hemostatic agents for controlling bleeding during surgery and to prevent post-operative rebleeding. A commercial RADA16 formulation is currently used for hemostasis in cardiovascular, gastrointestinal, and otorhinolaryngological surgical procedures, and studies are underway to investigate its use in wound healing and adhesion reduction. Straightforward application of viscous RADA16 into areas that are not easily accessible circumvents technical challenges in difficult-to-reach bleeding sites. The transparent hydrogel allows clear visualization of the surgical field and facilitates suture line assessment and revision. The shear-thinning and thixotropic properties of RADA16 allow its easy application through a narrow nozzle such as an endoscopic catheter. RADA16 hydrogels can fill tissue voids and do not swell so can be safely used in close proximity to pressure-sensitive tissues and in enclosed non-expandable regions. By definition, the synthetic peptide avoids potential microbiological contamination and immune responses that may occur with animal-, plant-, or mineral-derived topical hemostats. In vitro experiments, animal studies, and recent clinical experiences suggest that RADA16 nanofibrous hydrogels can act as surrogate extracellular matrices that support cellular behavior and interactions essential for wound healing and for tissue regenerative applications. In the future, the unique nature of RADA16 may also allow us to use it as a depot for precisely regulated drug and biopharmaceutical delivery.

Tolerance and osteointegration of TricOs(TM)/MBCP(®) in association with fibrin sealant in mastoid obliteration after canal wall-down technique for cholesteatoma.

CONCLUSION: The TricOs™/MBCP(®) and fibrin sealant composite was a convenient, effective, and well-tolerated material for mastoid cavity filling and immediate reconstruction of the external auditory meatus after cholesteatoma surgery with canal wall down (CWD). OBJECTIVE: To assess the tolerance and osteointegration of a bone graft substitute, TricOs™/MBCP(®), in association with fibrin sealant for filling the mastoid cavity after cholesteatoma surgery using the CWD technique. METHODS: In this prospective observational study 57 patients with cholesteatoma suitable for CWD were recruited from April 2006 to April 2008 and followed up for 1 year. The mastoid cavity was filled with TricOs™/MBCP(®) followed by immediate reconstruction of the external auditory meatus covered with fascia temporalis and/or cartilage. The main outcome was skin tolerance assessed by a novel weighted score emphasizing long-term results. The typical weighted reference score was 1.67; skin tolerance was considered acceptable if 75% of patients had a score ≤ 1.67. Secondary outcomes were otorrhea and/or otalgia, hearing, and osteointegration assessed through computed tomography scanning at 12 months. RESULTS: Forty-one patients had a complete follow-up; 34 (82.3%) patients achieved the main end point with scores ≤ 1.67. Otorrhea decreased postoperatively. No otalgia interfering with daily tasks was reported. Ossicular reconstruction was carried out in 29 patients. Absence of cochlear toxicity was confirmed by unimpaired bone conduction. Preoperative and postoperative speech audiometry results were similar. No serious adverse events were observed. Osteointegration was satisfactory with hyperdensity or intermediate density in 95% of patients at 12 months.

Tensile strength of biological fibrin sealants: a comparative study.

BACKGROUND: Fibrin sealants are commonly used in liver surgery, although their effectiveness in routine clinical practice remains controversial. Individual sealant characteristics are based on hemostatic effects and adhesion properties that can be experimentally measured using the 'rat skin test' or the 'pig skin test'. This study used a more relevant and realistic experimental canine model to compare the differences in the adhesive properties of four fibrin sealants in hepatectomy: Tisseel/Tissucol, Tachosil, Quixil, and Beriplast. MATERIALS AND METHODS: A partial hepatectomy was performed in beagle dogs under general anesthesia to obtain liver cross-sections. Fibrin sealants were allocated to dog livers using a Youden square design. The tensile strength measurement was performed using a traction system to measure the rupture stress point of a small wooden cylinder bonded to the liver cross-section. RESULTS: Significantly greater adhesion properties were observed with Tisseel/Tissucol compared with Quixil or Beriplast (P = 0.002 and 0.001, respectively). Similarly, Tachosil demonstrated significantly greater adhesive properties compared with Beriplast (P = 0.009) or Quixil (P = 0.014). No significant differences were observed between Tisseel/Tissucol and Tachosil or between Beriplast and Quixil. CONCLUSIONS: The results of this comparative study demonstrate that different fibrin sealants exhibit different adhesive properties. Tisseel/Tissucol and Tachosil provided greatest adhesion to liver cross-section in our canine model of hepatectomy. These results may enable the optimal choice of fibrin sealants for this procedure in clinical practice.

Comparison of two bone substitute biomaterials consisting of a mixture of fibrin sealant (Tisseel) and MBCP (TricOs) with an autograft in sinus lift surgery in sheep.

OBJECTIVES: The aim of this study was to assess the efficacy and safety of macroporous biphasic calcium phosphate (MBCP())/fibrin grafts (TricOs((R)))/(Tisseel((R))) for sinus lift augmentation in sheep. Autologous bone grafts were used as a positive control, and dental implants were placed to assess the efficiency of the composite. MATERIALS AND METHODS: A total of 12 adult sheep (24 maxillary sinuses) were randomized to receive sinus lift augmentation with MBCP()/fibrin grafts obtained by either simultaneous or sequential addition of thrombin and fibrinogen to MBCP(), or autologous bone grafts. Six months post-sinus lift surgery, dental implants were placed. At 6 months post-sinus lift and 3 months after dental implant placement, the characteristics of newly formed bone and dental implant stability were assessed. The methods used were radiography, scanning electron microscopy, light microscopy, micro-CT analysis, radio frequency analysis (RFA), and image analysis. RESULTS: There were no clinical adverse events in the post-operative period. New bone formation was similar for MBCP()/fibrin grafts and autografts at 21-20% and 20%, respectively, at 6 months, and at 34-35% and 35%, respectively, at 9 months. Implantability of dental implants was better at the time of placement with MBCP()/fibrin grafts than autografts at 81-88% and 69%, respectively. Three months after placement, RFA showed better implantability with MBCP()/fibrin grafts than with autografts at 75-82% and 71%, respectively. The bone contact measurements were around 50% for the three groups, without significant differences. CONCLUSIONS: This study shows that following sinus lift augmentation in sheep, MBCP()/fibrin grafts support new bone formation that is comparable to autografts, while providing better support for the dental implants.

In vivo biological performance of composites combining micro-macroporous biphasic calcium phosphate granules and fibrin sealant.

INTRODUCTION: Fibrin glues are currently used by surgeons and can facilitate the handling of biomaterials. Combining fibrin glue with calcium phosphate bioceramics gives a mouldable composite that cements the granules into the implantation site. In addition to the mechanical aspect of the composite, it has been suggested that the mixture also promotes wound healing. These human blood derivatives contain natural (aprotinin) or synthetic (tranexamic acid) antifibrinolytic substances. We compared the bioactivity of two composites combining calcium phosphate granules with two different types of fibrin glue, one with aprotinin and the other with tranexamic acid. MATERIALS AND METHODS: The composite was composed of fibrin glue (Tissucol) and 1 to 2 mm granules of biphasic calcium phosphate granules (MBCP) with a volume ratio of 1 for 2. Bone cavities were drilled in 12 New Zealand rabbits and filled with a composite with aprotinin-fibrin glue on the right condyle and one with tranexamic acid-fibrin glue on the left condyle. The rabbits were randomized into two groups: 3 and 6 weeks of delay. Light microscopy, scanning electron microscopy and image analysis were performed. RESULTS: No adverse reactions were observed in either sample. Bony ingrowth associated with bioceramic resorption by osteoclastic TRAP-positive cells was noted. No significant difference was observed between the two composites. The bony ingrowth and ceramic resorption were qualitatively and quantitatively similar with both composites. CONCLUSION: This study demonstrated that the choice of a natural (aprotinin) or synthetic (tranexamic acid) antifibrinolytic agent in the fibrin sealant associated with calcium phosphate granules and used as a bone substitute had no effect on the bioactivity of the composite. It remained efficient in bone reconstruction, no adverse effects were observed, and the bony ingrowth was qualitatively and quantitatively equivalent with the two types of fibrin sealant.

MBCP biphasic calcium phosphate granules and tissucol fibrin sealant in rabbit femoral defects: the effect of fibrin on bone ingrowth.

An ageing population implies an increase in bone and dental diseases, which are in turn a source of numerous handicaps. These pathologies are an expensive burden for the European health system. As no specific bioactive materials are efficient enough to cope with this burden, we have to develop an injectable, mouldable, self-hardening bone substitute to support bone tissue reconstruction and augmentation. New, highly bioactive and suitable biomaterials have been developed to replace bone grafts in orthopedic revision and maxillofacial surgery for bone augmentation. These mouldable, self-hardening materials are based on the association of MBCP Biphasic Calcium Phosphate Granules and Tissucol Fibrin Sealant. The in vivo evaluation of ingrowth in relation to the composite was made in an experiment on rabbits. The results indicate that in the presence of fibrin sealant, newly-formed bone developed at a small distance from the surface of the calcium phosphate ceramic. Two different bone apposition processes were identified. Without the fibrin component (MBCP group), bone rested directly on the surface of the granules. This observation is commonly described as osteoconduction in calcium phosphate materials. On the contrary, the presence of the fibrinogen component seemed to modify this standard osteoconduction phenomenon: the newly-formed bone essentially grew at a distance from the surface of the granules, on the fibrillar network, and could be considered as an inductive phenomenon for osteogenic cell differentiation from mesenchymal stem cells.

Biphasic ceramics and fibrin sealant for bone reconstruction in ear surgery.

Bone reconstruction is still a matter of concern in middle ear surgery despite the large number of surgical techniques proposed. A composite made of biphasic calcium phosphate ceramic granules mixed with human fibrin sealant, forming a moldable material that is easy to set for bone reconstruction, has been used with success over a 16-year period for reconstruction of the posterior canal wall or for mastoid obliteration. In a retrospective series of 72 ears with long-term follow-up (average follow-up of 46 months), regular microscopic examination, and computed tomographic controls, we have evaluated this bone reconstruction technique for radical mastoidectomy cavities or the closed technique. The bone reconstruction material provided an immediate anatomic reconstruction that remains stable and is well tolerated over the long term. A slight leakage of granules in the meatus was initially observed in several patients with transient aseptic otorrhea. Fifty-seven ears were followed up for 1 year or more. Satisfactory clinical results with complete regression of the mucous membrane disease were found in 82.4% of the patients, with perfect stability of the material in 65%. We did not observe any cases of recurrent cholesteatoma in or behind the filling material. Eighteen biopsies were performed between 8 and 84 months after surgery during a second surgical step performed for functional purposes or for recurrent cholesteatoma; 17 of the 18 cases showed osteointegration of the filling material. After a 16-year experiment, we consider this technique to be a highly satisfactory procedure that could be extended to other situations of bone reconstruction.