School of Materials Science and Engineering, Nanjing University of Science and Technology, 409 Room, 338 Building, 200 Xiao Ling Wei Street, Nanjing 210094, China.
School of Materials Science and Engineering, Nanjing University of Science and Technology, 409 Room, 338 Building, 200 Xiao Ling Wei Street, Nanjing 210094, China.
Acta Biomater. 2022 Nov;153:159-177. doi: 10.1016/j.actbio.2022.09.036. Epub 2022 Sep 22.
Injectable hydrogels based on various functional biocompatible materials have made rapid progress in the field of bone repair. In this study, a self-healing and injectable polysaccharide-based hydrogel was prepared for bone tissue engineering. The hydrogel was made of carboxymethyl chitosan (CMCS) and calcium pre-cross-linked oxidized gellan gum (OGG) cross-linked by the Schiff-base reaction. Meanwhile, magnetic hydroxyapatite/gelatin microspheres (MHGMs) were prepared by the emulsion cross-linking method. The antibacterial drugs, tetracycline hydrochloride (TH) and silver sulfadiazine (AgSD), were embedded into the MHGMs. To improve the mechanical and biological properties of the hydrogels, composite hydrogels were prepared by compounding hydroxyapatite (HAp) and drug-embedded MHGMs. The physical, chemical, mechanical and rheological properties of the composite hydrogels were characterized, as well as in vitro antibacterial tests and biocompatibility assays, respectively. Our results showed that the composite hydrogel with 6% (w/v) HAp and 10 mg/mL MHGMs exhibited good magnetic responsiveness, self-healing and injectability. Compared with the pure hydrogel, the composite hydrogel showed a 38.8% reduction in gelation time (196 to 120 s), a 65.6% decrease in swelling rate (39.4 to 13.6), a 51.9% increase in mass residual after degradation (79.5 to 120.8%), and a 143.7% increase in maximum compressive stress (53.6 to 130.6 KPa). In addition, this composite hydrogel showed good drug retardation properties and antibacterial effects against both S. aureus and E. coli. CCK-8 assay showed that composite hydrogel maintained high cell viability (> 87%) and rapid cell proliferation after 3 days, indicating that this smart hydrogel is expected to be an alternative scaffold for drug delivery and bone regeneration. STATEMENT OF SIGNIFICANCE: Biopolymer hydrogels have been considered as the promising materials for the treatment of tissue engineering and drug delivery. Injectable hydrogels with and self-healing properties and responsiveness to external stimuli have been extensively investigated as cell scaffolds and bone defects, due to their diversity and prolonged lifetime. Magnetism has also been involved in biomedical applications and played significant roles in targeted drug delivery and anti-cancer therapy. We speculate that development of dual cross-linked hydrogels basing biopolymers with multi-functionalities, such as injectable, self-healing, magnetic and anti-bacterial properties, would greatly broaden the application for bone tissue regeneration and drug delivery.
基于各种功能生物相容性材料的可注射水凝胶在骨修复领域取得了快速进展。在这项研究中，我们制备了一种自修复和可注射的多糖基水凝胶，用于骨组织工程。该水凝胶由羧甲基壳聚糖（CMCS）和经席夫碱反应交联的预交联氧化结冷胶（OGG）制成。同时，通过乳化交联法制备磁性羟磷灰石/明胶微球（MHGMs）。将抗菌药物盐酸四环素（TH）和磺胺嘧啶银（AgSD）包埋在 MHGMs 中。为了提高水凝胶的机械和生物学性能，通过复合羟磷灰石（HAp）和载药 MHGMs 制备了复合水凝胶。分别对复合水凝胶的物理、化学、力学和流变性能进行了表征，并进行了体外抗菌试验和生物相容性试验。结果表明，含有 6%（w/v）HAp 和 10mg/mL MHGMs 的复合水凝胶具有良好的磁响应性、自修复性和可注射性。与纯水凝胶相比，复合水凝胶的凝胶时间缩短了 38.8%（196 秒至 120 秒），溶胀率降低了 65.6%（39.4%至 13.6%），降解后的质量残留率增加了 51.9%（79.5%至 120.8%），最大压缩应力增加了 143.7%（53.6kPa 至 130.6kPa）。此外，该复合水凝胶具有良好的药物缓释性能和对金黄色葡萄球菌和大肠杆菌的抗菌效果。CCK-8 试验表明，复合水凝胶在第 3 天仍保持较高的细胞活力（>87%）和快速增殖，表明这种智能水凝胶有望成为药物输送和骨再生的替代支架。意义声明：生物聚合物水凝胶已被认为是组织工程和药物输送治疗的有前途的材料。具有可注射性、自修复性和对外界刺激的响应性的可注射水凝胶因其多样性和延长的寿命而被广泛研究作为细胞支架和骨缺损。磁性也已应用于生物医学领域，并在靶向药物输送和抗癌治疗中发挥了重要作用。我们推测，开发基于具有多种功能（如可注射、自修复、磁性和抗菌性）的生物聚合物的双重交联水凝胶，将极大地拓宽其在骨组织再生和药物输送方面的应用。
