RESUMEN
STUDY DESIGN: Burst strength study in porcine dural models and functional and histological study in rat dural models. OBJECTIVE: This study aimed to investigate the sealing strength and biocompatibility of Alaska pollock-derived gelatin (ApGltn) and fibrin sealants in disrupted dural injuries. SUMMARY OF BACKGROUND DATA: Disruption of the dura mater occurs during spine surgery, leading to cerebrospinal fluid leakage. Fibrin sealant is usually applied to ruptured sites; however, it lacks sealing strength. A novel biocompatible sealant composed of ApGltn was recently demonstrated to have good burst strength and biocompatibility in the porcine aorta. METHODS: Ten porcine dura maters with central holes were covered with ApGltn and fibrin sealants (five samples per group). The maximum burst strength of each sealant was measured, and histological examination was performed after burst testing. Twenty-seven dura maters of male Wistar rats were used for functional and histopathological evaluations. The rats were treated with three surgical interventions: defect + ApGltn sealant; defect + fibrin sealant; defect alone (nine rats per group). Macroscopic confirmation of the sealant, hindlimb motor function analysis, and histopathological examination were performed at two, four, and eight weeks after the procedure. RESULTS: The maximum burst strength of the ApGltn sealant was ~4.4 times higher than that of the fibrin sealant (68.1±12.1 vs . 15.6±8.7 mmHg; P <0.001). Histological examination confirmed that the ApGltn sealant showed tight adhesion to the dural surface, whereas a gap was observed between the fibrin sealant and the dura mater. In the rat model, the ApGltn sealant resulted in spinal function and dural histological findings similar to those of the fibrin sealant. CONCLUSION: The ApGltn sealant had a higher sealing strength than, and comparable effect on dura regeneration with, the fibrin sealant.
Asunto(s)
Duramadre , Adhesivo de Tejido de Fibrina , Gelatina , Ratas Wistar , Animales , Duramadre/cirugía , Duramadre/efectos de los fármacos , Ratas , Porcinos , Masculino , Materiales Biocompatibles , Adhesivos Tisulares , Ensayo de Materiales , Modelos Animales de Enfermedad , Pérdida de Líquido CefalorraquídeoRESUMEN
Adhesives/sealants are used after suturing to prevent leakage of cerebrospinal fluid from an anastomotic site. Commercial adhesives/sealants have been used to close the cerebral dura. However, swelling of the cured adhesives/sealants induces increased intracranial pressure and decreases the strength of the seal. In the present study, tissue adhesive hydrogels with improved swelling property using inclusion complex composed of α-cyclodextrin (αCD) and decyl group (C10)-modified Alaska pollock-derived gelatin (C10-ApGltn) with a high degree of substitution (DS) (>20 mol%) are developed. Viscosity of C10-ApGltn with a high DS solution remarkably decreased by the addition of αCD. The resulting αCD/C10-ApGltn adhesive hydrogel composed of αCD/C10-ApGltn inclusion complexes and poly(ethylene glycol) (PEG)-based crosslinker showed improved swelling property after immersion in saline. Also, the resulting adhesive has a significantly higher burst strength than fibrin-based adhesives and is as strong as a PEG-based adhesive. Quantitative analysis of αCD revealed that the improved swelling property of the resulting adhesive hydrogels is induced by the release of αCD from cured adhesive, and the subsequent assembly of decyl groups in the saline. These results suggest that adhesives developed using the αCD/C10-ApGltn inclusion complex can be useful for closing the cerebral dura mater.
Asunto(s)
Adhesivos Tisulares , alfa-Ciclodextrinas , Adhesivos Tisulares/farmacología , Hidrogeles/farmacología , Gelatina/farmacología , Alaska , Adhesivo de Tejido de Fibrina , AdhesivosRESUMEN
OBJECTIVES: Postoperative prolonged air leakage is a frequent complication following lung resection. We have shown the high adhesive quality of a newly developed sealant based on a hydrophobically modified Alaska pollock-derived gelatin (ApGltn) sealant in acute in vivo settings. The purpose of this study was to investigate the long-term efficacy and safety of ApGltn sealant using rats as a preclinical model. METHODS: An air leakage rat model with a 5-mm pleural defect was created, to which ApGltn sealant or fibrin sealant was applied. In both groups, the rats were evaluated on days 1, 7, 14 and 28. In the ApGltn sealant group, days 56 and 84 were added to evaluate absorption as sealant was still present on day 28. The number of rats in each subgroup was 4 (for a total of 40). Lung specimens and blood samples were obtained for histological and haematological assessment. RESULTS: No findings suggesting infection or air leakage were observed. ApGltn sealant was absorbed from day 56 to day 84. Histologically, although neutrophil and lymphocyte infiltrations on the lung side did not differ between groups, those on the sealant side were significantly less in the ApGltn sealant group. Blood sample tests revealed no significant findings suggesting inflammation or organ damage in either group. CONCLUSIONS: ApGltn sealant showed long-term sealing efficacy and safety with mild inflammation in a pulmonary air leakage rat model. ApGltn sealant is expected to be a safe and effective sealant for clinical applications.
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Enfermedades Pulmonares , Adhesivos Tisulares , Ratas , Animales , Gelatina/uso terapéutico , Adhesivos Tisulares/uso terapéutico , Alaska , Inflamación , Adhesivo de Tejido de Fibrina/uso terapéuticoRESUMEN
Aortic anastomotic leak is a potentially fatal complication that can occur after treatment of aortic dissection or aneurysm. Several surgical adhesives have been used to prevent this complication, but all have problems with regard to tissue adhesion or biocompatibility. In the present study, we developed a surgical adhesive composed of boric acid-protected catechol groups-modified Alaska pollock-derived gelatin (Cat-ApGltn) and a poly(ethylene glycol)-based crosslinker (4S-PEG). By avoiding oxidation of catechol groups using boric acid, resulting Cat-ApGltn adhesive formed a strong hydrogel by double crosslinking: chemical crosslinking by 4S-PEG, and chemical and physical crosslinking by the catechol groups. The catechol groups modification contributed to increased bulk strength and decreased gelation time/swelling ratios. The Cat-ApGltn adhesive, in which 7.8 mol% of the amino groups of the original ApGltn (Org-ApGltn) were modified with catechol groups, demonstrated 2.3 times higher burst strength compared with the Org-ApGltn adhesive, and 3.9 times higher burst strength compared with a commercial fibrin adhesive. When the Cat-ApGltn adhesive was implanted subcutaneously into rats, it induced only weak inflammation similar to that induced by the Org-ApGltn adhesive, and was completely degraded within 2 months. Therefore, the Cat-ApGltn adhesive has great potential for use in the field of cardiovascular surgery.
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Gelatina , Adhesivos Tisulares , Ratas , Animales , Gelatina/farmacología , Adhesivos Tisulares/farmacología , Alaska , Interacciones Hidrofóbicas e Hidrofílicas , Hidrogeles/farmacología , Adhesivos/farmacología , CatecolesRESUMEN
Air leakage is one of the major complications related to pulmonary surgeries. To reduce this complication, we developed a decyl group (C10)-modified Alaska pollock gelatin (ApGltn) (C10-ApGltn) sealant and evaluated its practical performance against commercially available sealants, Beriplast® and DuraSeal®. C10-ApGltn was synthesized by reductive amination of the amino groups in ApGltn with decanal. C10-ApGltn was crosslinked with a poly(ethylene glycol)-based crosslinker to form a tissue sealant. The crosslinking time of the C10-ApGltn sealant was fast enough for curing on tissue and application as a spray system. Although the percent swelling of C10-ApGltn and DuraSeal was significantly greater than Beriplast, C10-ApGltn and DuraSeal exhibited excellent tissue sealing properties on pleura tissue under a long-term moist condition. Additionally, C10-ApGltn and DuraSeal did not cause severe inflammatory responses in a rat subcutaneous example. Therefore, C10-ApGltn sealant had comparable tissue sealing properties to DuraSeal under a moist condition, indicating the potential of C10-ApGltn sealant for pulmonary surgeries.
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Gelatina , Adhesivos Tisulares , Animales , Gelatina/farmacología , Interacciones Hidrofóbicas e Hidrofílicas , Polietilenglicoles , Ratas , Adhesivos Tisulares/farmacologíaRESUMEN
BACKGROUND: Postoperative prolonged air leakage is a frequent complication after lung resection. We have developed a new sealant based on a hydrophobically modified Alaska pollock-derived gelatin (ApGltn) sealant. The purpose of this study was to evaluate the adhesive strength of the ApGltn sealant in comparison with a fibrin sealant using a new spray system in ex vivo and in vivo models. METHODS: Pleural defects in ex vivo and in vivo porcine models were created, to which the ApGltn sealant or the fibrin sealant was applied. The pressure resistance was assessed with a stepwise increase in airway pressure to confirm air leakage from the sealing site. Tissue samples covered with each sealant were obtained for histologic assessment. RESULTS: In the ex vivo experiment, the leak pressures of the ApGltn sealant were significantly greater than those of the fibrin sealant (102.94 ± 15.6 cm H2O and 28.37 ± 5.1 cm H2O, respectively) (P < .01). In the in vivo experiment, the leak pressures of the ApGltn sealant were also significantly greater than those of the fibrin sealant (68.82 ± 18.04 cm H2O and 43.33 ± 7.13 cm H2O, respectively) (P = .043). The histologic examination confirmed that the ApGltn sealant adhered tightly to both the pleura and the surface of the pleural defect. CONCLUSIONS: The ApGltn sealant has sufficiently high adhesive quality in ex vivo and in vivo porcine lungs, which could be considered suitable and effective for use in the prevention of air leakage from the lungs.
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Enfermedades Pulmonares , Adhesivos Tisulares , Alaska , Animales , Adhesivo de Tejido de Fibrina/uso terapéutico , Gelatina/uso terapéutico , Humanos , Porcinos , Adhesivos Tisulares/farmacología , Adhesivos Tisulares/uso terapéuticoRESUMEN
Anastomotic leakage and tissue adhesion are significant complications associated with colorectal surgeries, such as the resection of colorectal cancer. However, an effective biomedical apparatus has yet to be developed to address both complications. In the present study, we developed a tissue-sealing, anti-adhesive hydrogel composed of decyl group-modified gelatin (C10-ApGltn) and a poly (ethylene glycol)-based crosslinker. C10-ApGltn based hydrogel (C10-gel) demonstrated increased elastic modulus and suppressed swelling ratio compared with the unmodified ApGltn. Furthermore, C10-gel effectively sealed a water leakage model of intestine tissue and prevented contact between two intestinal tissue samples. In vivo experiments revealed that C10-gel degraded almost entirely in 28 days and prevented cell infiltration for 14 days, which effectively inhibits tissue adhesion. Therefore, C10-gel is a biocompatible hydrogel that can be used to mitigate or prevent anastomotic leakage and prevent tissue adhesion in colorectal surgery.