Sauce-Guevara Mildred A, García-Schejtman Sergio D, Alarcon Emilio I, Bernal-Chavez Sergio A, Mendez-Rojas Miguel A
Department of Chemical and Biological Sciences, Universidad de las Americas Puebla, Ex-Hacienda de Santa Catarina Martir s/n, San Andres Cholula, Puebla 72820, Mexico.
Bioengineering and Therapeutic Solutions (BEaTS) Program, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, Canada.
Pharmaceuticals (Basel). 2025 Apr 23;18(5):616. doi: 10.3390/ph18050616.
In tissue engineering, developing injectable hydrogels with tailored mechanical and bioactive properties remains a challenge. This study introduces an injectable hydrogel composite for soft tissue regeneration, composed of oxidized alginate (OA) and N-succinyl chitosan (NSC) cross-linked via Schiff base reaction, reinforced with graphene oxide (GOx) and cyclic arginylglycylaspartic acid (c-RGD). The objective was to create a multifunctional platform combining injectability, bioactivity, and structural stability. The OA/NSC/GOx-cRGD hydrogel was synthesized through Schiff base cross-linking (aldehyde-amine reaction). Characterization included FTIR (C=N bond at 1650 cm⁻¹), Raman spectroscopy (D/G bands at 1338/1567 cm⁻¹), SEM (porous microstructure), and rheological analysis (shear-thinning behavior). In vitro assays assessed fibroblast viability (MTT) and macrophage secretion (ELISA), while ex-vivo injectability and retention were evaluated using chicken cardiac tissue. The hydrogel exhibited shear-thinning behavior (viscosity: 10 to <1 Pa·s) and elastic-dominated mechanics (G' > G″), ensuring injectability. SEM revealed an interconnected porous structure mimicking native extracellular matrix. Fibroblast viability remained ≥95%, and secretion in macrophages decreased by 80% (30 vs. 150 pg/μL in controls), demonstrating biocompatibility and anti-inflammatory effects. The hydrogel adhered stably to cardiac tissue without leakage. The OA/NSC/GOx-cRGD composite integrates injectability, bioactivity, and structural stability, offering a promising scaffold for tissue regeneration. Its modular design allows further functionalization with peptides or growth factors. Future work will focus on translational applications, including scalability and optimization for dynamic biological environments.
在组织工程中,开发具有定制机械和生物活性特性的可注射水凝胶仍然是一项挑战。本研究介绍了一种用于软组织再生的可注射水凝胶复合材料,它由通过席夫碱反应交联的氧化海藻酸盐(OA)和N-琥珀酰壳聚糖(NSC)组成,并用氧化石墨烯(GOx)和环化精氨酰甘氨酰天冬氨酸(c-RGD)增强。目的是创建一个结合可注射性、生物活性和结构稳定性的多功能平台。OA/NSC/GOx-cRGD水凝胶通过席夫碱交联(醛-胺反应)合成。表征包括傅里叶变换红外光谱(1650 cm⁻¹处的C=N键)、拉曼光谱(1338/1567 cm⁻¹处的D/G带)、扫描电子显微镜(多孔微观结构)和流变学分析(剪切变稀行为)。体外试验评估了成纤维细胞活力(MTT)和巨噬细胞分泌(酶联免疫吸附测定),而使用鸡心脏组织评估了离体可注射性和保留情况。该水凝胶表现出剪切变稀行为(粘度:10至<1 Pa·s)和以弹性为主的力学性能(G' > G″),确保了可注射性。扫描电子显微镜显示出模仿天然细胞外基质的相互连接的多孔结构。成纤维细胞活力保持≥95%,巨噬细胞分泌减少了80%(对照组为150 pg/μL,试验组为30 pg/μL),证明了生物相容性和抗炎作用。该水凝胶稳定地粘附在心脏组织上且无渗漏。OA/NSC/GOx-cRGD复合材料整合了可注射性、生物活性和结构稳定性,为组织再生提供了一个有前景的支架。其模块化设计允许用肽或生长因子进行进一步功能化。未来的工作将集中在转化应用上,包括扩大规模和针对动态生物环境进行优化。