Thirupathi Kumara Raja S, Thiruselvi T, Aravindhan R, Mandal Asit Baran, Gnanamani A
Microbiology Division, CSIR-CLRI, Adyar, Chennai, Tamil Nadu, India.
J Mater Chem B. 2015 Feb 21;3(7):1230-1244. doi: 10.1039/c4tb01196a. Epub 2014 Dec 17.
Imparting functional properties on a biomaterial for high end applications is always a challenging task. In the present study, an attempt was made to construct an injectable hydrogel through bioconjugation of dihydroxy phenolic acids to a gelatin backbone. Bioconjugating caffeic acid with gelatin followed by oxidation with mild oxidation agents provided a hydrogel with all the requisite properties (biocompatibility, controlled biodegradability, and antioxidant, antimicrobial and wound healing ability). Bioconjugation was performed using EDC/NHS and the resultant gel named as caffeic acid bioconjugated gel (CBG gel). The physicochemical, rheological, swelling, in vitro (biocompatibility, biodegradability, antimicrobial properties, antioxidant properties and drug release properties) and in vivo (biocompatibility, biodegradability and wound healing properties) studies on the CBG gel were carried out using standard protocols. The bioconjugation was confirmed by H NMR and UV-Vis analysis. Rheological analysis of the CBG gel revealed that the storage modulus was greater than the loss modulus at all the frequencies and suggested the elastic nature of the gel. About 50% weight gain within 12 hours during swelling studies and 50% weight loss within 12 hours during evaporation suggested the suitability of the CBG gel as a drug carrier. The drug release studies implied that there was an initial burst and later the release was sustained. The CBG gel promotes cell migration and demonstrates radical scavenging behavior. When subcutaneously injected into the animal, as in situ CBG gel, the gel was highly biocompatible and did not cause any necrosis. The crosstalk with adjacent tissue cells was smooth and the gel completely degraded within 24 days. The wound healing efficacy on full-thickness wounds suggested that the CBG gel accelerated healing and imparted high strength on the healed skin at an appreciable level. With all these additional functional properties, the CBG gel could be useful for biomedical applications.
赋予生物材料高端应用所需的功能特性始终是一项具有挑战性的任务。在本研究中,尝试通过将二羟基酚酸生物共轭到明胶主链上来构建一种可注射水凝胶。将咖啡酸与明胶进行生物共轭,然后用温和的氧化剂氧化,得到了一种具有所有必要特性(生物相容性、可控的生物降解性以及抗氧化、抗菌和伤口愈合能力)的水凝胶。使用EDC/NHS进行生物共轭,所得凝胶命名为咖啡酸生物共轭凝胶(CBG凝胶)。采用标准方案对CBG凝胶进行了物理化学、流变学、溶胀、体外(生物相容性、生物降解性、抗菌性能、抗氧化性能和药物释放性能)以及体内(生物相容性、生物降解性和伤口愈合性能)研究。通过¹H NMR和紫外可见光谱分析证实了生物共轭。CBG凝胶的流变学分析表明,在所有频率下储能模量均大于损耗模量,表明该凝胶具有弹性。溶胀研究表明,在12小时内重量增加约50%,蒸发研究表明,在12小时内重量损失50%,这表明CBG凝胶适合作为药物载体。药物释放研究表明,存在初始突释,随后释放持续。CBG凝胶促进细胞迁移并表现出自由基清除行为。当作为原位CBG凝胶皮下注射到动物体内时,该凝胶具有高度生物相容性,不会引起任何坏死。与相邻组织细胞的相互作用顺畅,凝胶在24天内完全降解。对全层伤口的伤口愈合效果表明,CBG凝胶加速了愈合,并在相当程度上使愈合后的皮肤具有高强度。具备所有这些额外的功能特性后,CBG凝胶可用于生物医学应用。