| Objective: Heparin is widely applied in clinical practice. Its main physiologicalfunction includes anticoagulation, antithrombus, inhibiting platelet adhesion,regulating blood lipids, and it can act on multiple aspects of the complement systemto suppress excessive activation system. In addition, study found that heparin hasanti-inflammatory effects, and can inhibit the growth of fibroblast and lens epithelialcell. In addition, heparin can inhibit the incidence of capsular opacification to acertain extent, which leads to an application in ophthalmology. However, for heparinis not stable in the body and need frequent injections, to establish a long-term, stableadministration has a great significance. Heparin-release material can maintain theconcentration of heparin in the administration site, and has a less damage to thepatient. Containing heparin tissue engineering material has been applied to theartificial blood vessels and the treatment of myocardial infarction and cataracts.However, the materials applied currently are limited by the mechanical strength, therate of sustained release, the release time, the degradation rate, the immune rejectionand so on.Therefore, the experiment is to find an excellent material to serve asheparin sustained release carrier material, in order to obtain a material with certainmechanical strength, durable heparin-release capability, good biocompatibility andcan degrade gradually, to providing experimental evidence for the sustained release ofheparin administration.Methods:(1) Prepare heparin-hydroxyethyl chitosan membrane and heparin-Gelatin membrane, which was crosslinked by1,4-butanediol diglycidyl ether.Evaluate the mechanical strength, water absorption, swelling ratio and heparinbinding ratio of the two membranes to select the optimum material. (2) Select the optimum mixed-linked carrier and laying heparin, to prepare differentdegree of crosslinking of different materials than the diaphragm, the mechanicalstrength of the membrane, water absorption, swelling ratio and heparin binding,heparin was evaluated in vitro sustained release property, select the optimum degreeof crosslinking and material ratio.(3) Evaluate the biocompatibility and degradation in vivo of the optimum membrane,include cytotoxicity, cell compatibility and tissue compatibility and biologicaldegradation rate in rat subcutaneous and leg muscles.Results:(1) Heparin-Gelatin membrane has a superior mechanical strength, heparinbinding rate than gelatin-hydroxyethyl chitosan membrane, so this experimentselected gelatin as a sustained release carrier.(2) After screening, two membrane, a#(Gelatin: heparin=3:2, the degree ofcrosslinking was10:1), b#（Gelatin: heparin=3:2, the degree of crosslinking was20:1）, had good mechanical properties and sustained heparin releasing effect with31d-cumulative heparin releasing concentrations of401μg/mL and635μg/mL.(3) The cytotoxicity of a#and b#membrane was compliance with the requirements ofthe body implant. The membrane surface can significantly inhibit the growth of L929cells. And the membrane has a preferably histocompatibility. The degradation time ofthe membrane in rats was about12weeks.Conclusions: In this study, a biodegradable membrane material can sustained releaseheparin was prepared. The material is easy to prepare, and it has a good mechanicalproperties, they can release heparin in a high rate with a lasting effect. And thematerials’ tissue compatibility were good and could significantly inhibit the growth ofL929fibroblast cells. It is expected to have a good application prospect in terms ofophthalmic tissue engineering materials. |
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