邻苯二酚/微纤维胶原止血水凝胶的制备及其性能研究

Preparation and characterization of catechol/microporous collagen hemostatic hydrogel

目的:将邻苯二酚共聚物与微纤维胶原结合制备水凝胶止血材料,提高高湿环境下战创伤的快速止血效果。方法:基于贻贝仿生技术,利用3,4-二甲氧基苯乙烯(3,4-dimethoxystyrene,DMS)与4-乙烯基苯甲酸(4-vinyl benzoic acid,VBA)通过过硫酸钾引发聚合,经甲氧基脱保护后制备邻苯二酚共聚物P(DHS-co-VBA)。利用凝胶渗透色谱、核磁共振氢谱和傅里叶变换红外光谱等对P(DHS-co-VBA)材料进行表征,评价P(DHS-co-VBA)是否制备成功。将微纤维胶原与制备的P(DHS-co-VBA)共混,制备P(DHS-co-VBA)/微纤维胶原水凝胶材料,评价P(DHS-co-VBA)/微纤维胶原水凝胶材料的亲疏水性能、湿黏附效果及细胞毒性。通过体外凝血实验及兔肝损伤模型止血实验,对P(DHS-co-VBA)/微纤维胶原水凝胶在湿面组织的止血效果进行评价。结果:凝胶渗透色谱、核磁共振氢谱和傅里叶变换红外光谱结果表明,P(DHS-co-VBA)制备成功。实验表明P(DHS-co-VBA)/微纤维胶原水凝胶材料较为亲水,细胞毒性低,具有良好的生物相容性,且湿黏附能力优异。动物实验表明,P(DHS-co-VBA)/微纤维胶原水凝胶材料的止血时间短且失血量少,止血效果较好。结论:制备的邻苯二酚/微纤维胶原止血水凝胶在高强黏附、快速止血、封闭创面方面表现出优异的性能,有望实现高湿环境下战创伤的快速止血,进一步提升我军的卫勤保障能力。

Objective To prepare a hydrogel hemostatic material by combining catechol polymer with microfibrillar collagen to improve rapid hemostasis of combat wounds in the high humidity environment.Methods Based on mussel mimicry catechol copolymers(P(DHS-co-VBA))were made using 3,4-dimethoxystyrene(DMS)and 4-vinyl benzoic acid(VBA)by potassium persulfate initiated polymerization after methoxy deprotection.Gel permeation chromatography,nuclear magnetic resonance hydrogen spectroscopy and Fourier transform infrared spectroscopy were used to evaluate whether P(DHS-co-VBA)material was prepared successfully.The microfibrillar collagen was blended with the prepared P(DHS-co-VBA)to obtain P(DHS-co-VBA)/microfibrillar collagen hydrogel material,and the hydrophilic properties,wet adhesionand cytotoxicity of P(DHS-co-VBA)/microfibrillar collagen hydrogel material were evaluated.The hemostatic effect of P(DHS-co-VBA)/microfibrillar collagen hydrogel in wet surface was assessed by the in vitro coagulation assay and the hemostasis assay of the rabbit liver injury model.Results The results of gel permeation chromatography,nuclear magnetic resonance hydrogen spectroscopy and Fourier transform infrared spectroscopy proved that P(DHS-co-VBA)material was prepared successfully.The experiments showed that the P(DHS-co-VBA)/microfibrillar collagen hydrogel material had high hydrophilicity,low cytotoxicity,high biocompatibility and excellent wet adhesion ability.Animal experiments indicated that the P(DHS-co-VBA)/microfibrillar collagen hydrogel material had short hemostatic time,low blood loss and high hemostatic effect.Conclusion The P(DHS-co-VBA)/microfibrillar collagen hydrogel material prepared has excellent performances in high strength adhesion,rapid hemostasis and closed wound.It is expected to achieve rapid hemostasis in war wounds under the high humidity environment and further enhance medical support ability of the PLA.