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Evaluation of a novel thermosensitive heparin-poloxamer hydrogel for improving vascular anastomosis quality and safety in a rabbit model.

Zhao YZ, Lv HF, Lu CT, Chen LJ, Lin M, Zhang M, Jiang X, Shen XT, Jin RR, Cai J, Tian XQ, Wong HL - PLoS ONE (2013)

Bottom Line: Our results showed that HP copolymer displayed special gel-sol-gel phase transition behavior with increasing temperature from 5 to 60 °C.In animal studies, imaging and histological examination of rabbit common jugular artery confirmed that HP hydrogel group had similar equivalent patency, flow and burst strength as Poloxamer 407 group.Moreover, HP hydrogel was superior to poloxamer 407 hydrogel and hand-sewn method for restoring the functions and epithelial structure of the broken vessel junctions after operation.

View Article: PubMed Central - PubMed

Affiliation: Wenzhou Medical University, Wenzhou City, Zhejiang Province, China ; College of Medicine, Drexel University, Philadelphia, Pennsylvania, United States of America.

ABSTRACT
Despite progress in the design of advanced surgical techniques, stenosis recurs in a large percentage of vascular anastomosis. In this study, a novel heparin-poloxamer (HP) hydrogel was designed and its effects for improving the quality and safety of vascular anastomosis were studied. HP copolymer was synthesized and its structure was confirmed by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ((1)H-NMR). Hydrogels containing HP were prepared and their important characteristics related to the application in vascular anastomosis including gelation temperature, rheological behaviour and micromorphology were measured. Vascular anastomosis were performed on the right common carotid arteries of rabbits, and the in vivo efficiency and safety of HP hydrogel to achieve vascular anastomosis was verified and compared with Poloxamer 407 hydrogel and the conventional hand-sewn method using Doppler ultrasound, CT angiograms, scanning electron microscopy (SEM) and histological technique. Our results showed that HP copolymer displayed special gel-sol-gel phase transition behavior with increasing temperature from 5 to 60 °C. HP hydrogel prepared from 18 wt% HP solution had a porous sponge-like structure, with gelation temperature at approximately 38 °C and maximum elastic modulus at 10,000 Pa. In animal studies, imaging and histological examination of rabbit common jugular artery confirmed that HP hydrogel group had similar equivalent patency, flow and burst strength as Poloxamer 407 group. Moreover, HP hydrogel was superior to poloxamer 407 hydrogel and hand-sewn method for restoring the functions and epithelial structure of the broken vessel junctions after operation. By combining the advantages of heparin and poloxamer 407, HP hydrogel holds high promise for improving vascular anastomosis quality and safety.

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Procedures of medical adhesive anastomosis combined with HP hydrogel.(A: Fractured vessels; B: Liquid HP was introduced into one side of the broken vessel; C: Liquid HP was introduced into the other side of the broken vessel, and transferred into solid phase under controlling environmental temperature; D: Alignment of HP perfused vessels; E: Coating of cyanoacrylate on the outer periphery of the vascular junction; F:HP was transferred from solid to liquid under in vivo temperature, and blood flowed through the anastomosis junction).
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pone-0073178-g002: Procedures of medical adhesive anastomosis combined with HP hydrogel.(A: Fractured vessels; B: Liquid HP was introduced into one side of the broken vessel; C: Liquid HP was introduced into the other side of the broken vessel, and transferred into solid phase under controlling environmental temperature; D: Alignment of HP perfused vessels; E: Coating of cyanoacrylate on the outer periphery of the vascular junction; F:HP was transferred from solid to liquid under in vivo temperature, and blood flowed through the anastomosis junction).

Mentions: Medical adhesive anastomosis: The HP hydrogel formulation or poloxamer 407 hydrogel formulation (see Table 1) was heated above the transition temperature and infused it into the divided blood vessel ends to maintain an open lumen. The procedures of medical adhesive anastomosis combined with poloxamer 407 or HP hydrogel were shown in Figure 2. A radiant halogen heat source was used to maintain the surgical field temperature precisely above the phase-transition temperature to achieve the maximum elastic modulus, but below the 43°C threshold where thermal damage occurs. After precise approximation of the intimal layer of the vessel, we applied 2-octylcyanoacrylate solution without dilution in a circumferential manner to complete the anastomosis. On removal of the heat source, the temperature of the operative field quickly returned to ambient temperatures (below the poloxamer transition temperature). Patency was assessed with a milking test immediately following removal of the vascular clamps. Once the anastomosis had been completed, wound muscle layers were sutured closed with 4/0 Vicryl Rapide, and the skin was closed with 2/0 Vicryl Rapide. For all animals the time taken from the moment the vascular was clamped until the clamps were released was noted. After surgery the animals received 0.5 mg/kg amoxicillin and clavulanic acid injected subcutaneously as a bolus antibiotic prophylaxis. Pain management consisted of a single subcutaneous dose of 0.03 mg/kg buprenorphine as motor function returned.


Evaluation of a novel thermosensitive heparin-poloxamer hydrogel for improving vascular anastomosis quality and safety in a rabbit model.

Zhao YZ, Lv HF, Lu CT, Chen LJ, Lin M, Zhang M, Jiang X, Shen XT, Jin RR, Cai J, Tian XQ, Wong HL - PLoS ONE (2013)

Procedures of medical adhesive anastomosis combined with HP hydrogel.(A: Fractured vessels; B: Liquid HP was introduced into one side of the broken vessel; C: Liquid HP was introduced into the other side of the broken vessel, and transferred into solid phase under controlling environmental temperature; D: Alignment of HP perfused vessels; E: Coating of cyanoacrylate on the outer periphery of the vascular junction; F:HP was transferred from solid to liquid under in vivo temperature, and blood flowed through the anastomosis junction).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3755001&req=5

pone-0073178-g002: Procedures of medical adhesive anastomosis combined with HP hydrogel.(A: Fractured vessels; B: Liquid HP was introduced into one side of the broken vessel; C: Liquid HP was introduced into the other side of the broken vessel, and transferred into solid phase under controlling environmental temperature; D: Alignment of HP perfused vessels; E: Coating of cyanoacrylate on the outer periphery of the vascular junction; F:HP was transferred from solid to liquid under in vivo temperature, and blood flowed through the anastomosis junction).
Mentions: Medical adhesive anastomosis: The HP hydrogel formulation or poloxamer 407 hydrogel formulation (see Table 1) was heated above the transition temperature and infused it into the divided blood vessel ends to maintain an open lumen. The procedures of medical adhesive anastomosis combined with poloxamer 407 or HP hydrogel were shown in Figure 2. A radiant halogen heat source was used to maintain the surgical field temperature precisely above the phase-transition temperature to achieve the maximum elastic modulus, but below the 43°C threshold where thermal damage occurs. After precise approximation of the intimal layer of the vessel, we applied 2-octylcyanoacrylate solution without dilution in a circumferential manner to complete the anastomosis. On removal of the heat source, the temperature of the operative field quickly returned to ambient temperatures (below the poloxamer transition temperature). Patency was assessed with a milking test immediately following removal of the vascular clamps. Once the anastomosis had been completed, wound muscle layers were sutured closed with 4/0 Vicryl Rapide, and the skin was closed with 2/0 Vicryl Rapide. For all animals the time taken from the moment the vascular was clamped until the clamps were released was noted. After surgery the animals received 0.5 mg/kg amoxicillin and clavulanic acid injected subcutaneously as a bolus antibiotic prophylaxis. Pain management consisted of a single subcutaneous dose of 0.03 mg/kg buprenorphine as motor function returned.

Bottom Line: Our results showed that HP copolymer displayed special gel-sol-gel phase transition behavior with increasing temperature from 5 to 60 °C.In animal studies, imaging and histological examination of rabbit common jugular artery confirmed that HP hydrogel group had similar equivalent patency, flow and burst strength as Poloxamer 407 group.Moreover, HP hydrogel was superior to poloxamer 407 hydrogel and hand-sewn method for restoring the functions and epithelial structure of the broken vessel junctions after operation.

View Article: PubMed Central - PubMed

Affiliation: Wenzhou Medical University, Wenzhou City, Zhejiang Province, China ; College of Medicine, Drexel University, Philadelphia, Pennsylvania, United States of America.

ABSTRACT
Despite progress in the design of advanced surgical techniques, stenosis recurs in a large percentage of vascular anastomosis. In this study, a novel heparin-poloxamer (HP) hydrogel was designed and its effects for improving the quality and safety of vascular anastomosis were studied. HP copolymer was synthesized and its structure was confirmed by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ((1)H-NMR). Hydrogels containing HP were prepared and their important characteristics related to the application in vascular anastomosis including gelation temperature, rheological behaviour and micromorphology were measured. Vascular anastomosis were performed on the right common carotid arteries of rabbits, and the in vivo efficiency and safety of HP hydrogel to achieve vascular anastomosis was verified and compared with Poloxamer 407 hydrogel and the conventional hand-sewn method using Doppler ultrasound, CT angiograms, scanning electron microscopy (SEM) and histological technique. Our results showed that HP copolymer displayed special gel-sol-gel phase transition behavior with increasing temperature from 5 to 60 °C. HP hydrogel prepared from 18 wt% HP solution had a porous sponge-like structure, with gelation temperature at approximately 38 °C and maximum elastic modulus at 10,000 Pa. In animal studies, imaging and histological examination of rabbit common jugular artery confirmed that HP hydrogel group had similar equivalent patency, flow and burst strength as Poloxamer 407 group. Moreover, HP hydrogel was superior to poloxamer 407 hydrogel and hand-sewn method for restoring the functions and epithelial structure of the broken vessel junctions after operation. By combining the advantages of heparin and poloxamer 407, HP hydrogel holds high promise for improving vascular anastomosis quality and safety.

Show MeSH
Related in: MedlinePlus