Tissue Engineering and Regenerative Medicine Laboratory, Department of Biomedical Engineering, International University, Vietnam National University-Ho Chi Minh City (VNU-HCM), 700000, Viet Nam.
Tissue Engineering and Regenerative Medicine Laboratory, Department of Biomedical Engineering, International University, Vietnam National University-Ho Chi Minh City (VNU-HCM), 700000, Viet Nam.
Mater Sci Eng C Mater Biol Appl. 2019 Oct;103:109670. doi: 10.1016/j.msec.2019.04.049. Epub 2019 Apr 25.
The purpose of this research is to investigate the effect of different oxidation degrees and volume ratios of components on the physical properties and biocompatibility of an in situ cross-linking chitosan-hyaluronic acid-based hydrogel for skin wound healing applications. Carboxymethyl groups (-CHCOOH) were introduced to the polymer chain of chitosan, producing N,O - Carboxymethyl Chitosan (NOCC). Hyaluronic acid was oxidized to obtain aldehyde hyaluronic acid (AHA) with three oxidation degrees (AHA40, AHA50 and AHA60). The gelation was induced by forming Schiff base linkage between aldehyde groups of AHA and amino groups of NOCC. Then, the polysaccharide derivatives were combined at three NOCC:AHA volume ratios (3:7, 5:5 and 7:3) to form composite hydrogels without using any additional cross-linker. FT-IR analysis, surface morphology observation and wettability test, in vitro degradation test and rheological analysis were carried out to characterize the hydrogels. Additionally, in vitro cytotoxicity and in vivo wound healing evaluations were also conducted to study the biocompatibility of the composite. Our findings showed that when increasing the volume of NOCC, the homogeneity and hydrophobicity of the resulting hydrogels were also improved and their pore walls became thicker, leading to slower degradation rate. On the other hand, when raising the oxidation degree of AHA, the hydrophilicity of the gels decreased and less time was required to form the gel matrix. Besides, the obtained in vitro and in vivo results indicated that lower oxidation degree of AHA supports cell proliferation, cell attachment and wound healing process better. It is also concluded that NOCC-AHA40 5:5 hydrogel is most suitable for skin wound healing applications since it possesses superior morphology with high uniformity, favorable pore size and suitable density along with appropriate wettability. The NOCC-AHA gel matrix is expected to be used as a delivery system for other factors and employed as an effective bio-glue in further tissue engineering applications.
本研究旨在探讨不同氧化程度和组分体积比对用于皮肤伤口愈合应用的原位交联壳聚糖-透明质酸水凝胶的物理性能和生物相容性的影响。壳聚糖的聚合物链上引入了羧甲基基团（-CHCOOH），生成 N,O-羧甲基壳聚糖（NOCC）。透明质酸被氧化，得到三种氧化程度（AHA40、AHA50 和 AHA60）的醛基透明质酸（AHA）。AHA 的醛基与 NOCC 的氨基之间形成席夫碱键，引发凝胶化。然后，将多糖衍生物以三种 NOCC:AHA 体积比（3:7、5:5 和 7:3）结合，形成无需使用任何额外交联剂的复合水凝胶。通过傅里叶变换红外光谱（FT-IR）分析、表面形貌观察和润湿性测试、体外降解试验和流变学分析对水凝胶进行了表征。此外，还进行了体外细胞毒性和体内伤口愈合评价，以研究复合材料的生物相容性。研究结果表明，随着 NOCC 体积的增加，所得水凝胶的均匀性和疏水性也得到提高，其孔壁变厚，导致降解速率变慢。另一方面，随着 AHA 氧化程度的提高，凝胶的亲水性降低，形成凝胶基质所需的时间也减少。此外，获得的体外和体内结果表明，较低氧化程度的 AHA 更有利于细胞增殖、细胞附着和伤口愈合过程。研究还得出结论，NOCC-AHA40 5:5 水凝胶最适合用于皮肤伤口愈合应用，因为它具有高均匀性、良好的孔径和适宜的密度，以及适宜的润湿性。NOCC-AHA 凝胶基质有望作为其他因素的递送系统，并在进一步的组织工程应用中用作有效的生物胶。
