Zong Hongjie, Wang Bo, Li Guifei, Yan Shifeng, Zhang Kunxi, Shou Yufeng, Yin Jingbo
Department of Polymer Materials, School of Materials Science and Engineering, Shanghai University, No. 99 Shangda Road, Shanghai 200444, P. R. China.
ACS Biomater Sci Eng. 2020 Aug 10;6(8):4702-4713. doi: 10.1021/acsbiomaterials.0c00915. Epub 2020 Jul 27.
Currently, biodegradable hydrogels are one of the most promising materials in tissue engineering. From the perspective of clinical needs, hydrogels with high strength and minimally invasive implantation are preferred for the reconstruction of load-bearing tissues. In this work, a biodegradable, high-strength, and injectable hydrogel was developed by one-step photo-cross-linking of two biomacromolecules, polyethylene glycol acrylated poly(l-glutamic acid) (PLGA-APEG) and methacrylated gellan gum (GG-MA). The hydrogels, named as PLGA/GG hydrogels, exhibited high mechanical properties. The compression stress of the hydrogels was 0.53 MPa, and the fracture energy was 7.7 ± 0.2 kJ m. Meanwhile, the storage modulus could reach 44.0 ± 0.6 kPa. The hydrogel precursor solution loaded with adipose-derived stem cells (ASCs) was subcutaneously injected into C57BL/6 mice and then cross-linked via in situ transdermal irradiation, which demonstrated the excellent injectability and subcutaneous gelatinization of PLGA/GG hydrogels as cell carriers. Furthermore, three-dimensional encapsulation of ASCs in hydrogels after 7, 14, and 21 days showed outstanding cytocompatibility, and the viability of ASCs was up to 84.0 ± 1.7%. The PLGA/GG hydrogels exhibited ideal behaviors of degradation, with 60 ± 5% of hydrogels degraded in phosphate buffered solution (PBS) after 11 weeks. H&E staining demonstrated that the hydrogels degraded gradually after 6 weeks and supported tissue invasion without inflammatory reactions, which indicated the laudable biodegradability of hydrogels. Hence, the biodegradable and high-strength hydrogels with well-performed injectability and biocompatibility possessed high potential applications in tissue engineering, especially in load-bearing tissue regeneration.
目前,可生物降解水凝胶是组织工程中最具前景的材料之一。从临床需求的角度来看,具有高强度和微创植入特性的水凝胶更适合用于承重组织的重建。在这项工作中,通过对两种生物大分子,即聚乙二醇丙烯酸化聚(L-谷氨酸)(PLGA-APEG)和甲基丙烯酸化结冷胶(GG-MA)进行一步光交联,制备了一种可生物降解、高强度且可注射的水凝胶。这种水凝胶被命名为PLGA/GG水凝胶,具有较高的力学性能。水凝胶的压缩应力为0.53MPa,断裂能为7.7±0.2kJ/m。同时,储能模量可达44.0±0.6kPa。将负载脂肪干细胞(ASCs)的水凝胶前体溶液皮下注射到C57BL/6小鼠体内,然后通过原位经皮照射进行交联,这证明了PLGA/GG水凝胶作为细胞载体具有出色的可注射性和皮下凝胶化性能。此外,在7天、14天和21天后,水凝胶中ASCs的三维包封显示出优异的细胞相容性,ASCs的活力高达84.0±1.7%。PLGA/GG水凝胶表现出理想的降解行为,11周后在磷酸盐缓冲溶液(PBS)中有60±5%的水凝胶发生降解。苏木精-伊红(H&E)染色表明,6周后水凝胶逐渐降解,并支持组织侵入且无炎症反应,这表明水凝胶具有良好的生物降解性。因此,这种具有良好可注射性和生物相容性的可生物降解高强度水凝胶在组织工程中,尤其是在承重组织再生方面具有很高的潜在应用价值。