Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, 94305, USA.
Adv Healthc Mater. 2019 Mar;8(5):e1801147. doi: 10.1002/adhm.201801147. Epub 2019 Feb 4.
Hydrogels have emerged as a diverse class of biomaterials offering a broad range of biomedical applications. Specifically, injectable hydrogels are advantageous for minimally invasive delivery of various therapeutics and have great potential to treat a number of diseases. However, most current injectable hydrogels are limited by difficult and time-consuming fabrication techniques and are unable to be delivered through long, narrow catheters, preventing extensive clinical translation. Here, the development of an easily-scaled, catheter-injectable hydrogel utilizing a polymer-nanoparticle crosslinking mechanism is reported, which exhibits notable shear-thinning and self-healing behavior. Gelation of the hydrogel occurs immediately upon mixing the biochemically modified hyaluronic acid polymer with biodegradable nanoparticles and can be easily injected through a high-gauge syringe due to the dynamic nature of the strong, yet reversible crosslinks. Furthermore, the ability to deliver this novel hydrogel through a long, narrow, physiologically-relevant catheter affixed with a 28-G needle is highlighted, with hydrogel mechanics unchanged after delivery. Due to the composition of the gel, it is demonstrated that therapeutics can be differentially released with distinct elution profiles, allowing precise control over drug delivery. Finally, the cell-signaling and biocompatibility properties of this innovative hydrogel are demonstrated, revealing its wide range of therapeutic applications.
水凝胶作为一类具有广泛生物医学应用的生物材料已经崭露头角。具体来说，可注射水凝胶有利于各种治疗药物的微创输送，并且具有治疗许多疾病的巨大潜力。然而，大多数现有的可注射水凝胶受到制造技术困难且耗时的限制，并且无法通过长而窄的导管输送，从而阻止了广泛的临床转化。在这里，报告了一种利用聚合物-纳米粒子交联机制的易于规模化、可通过导管注射的水凝胶的开发，该水凝胶表现出明显的剪切变稀和自修复行为。水凝胶的凝胶化在将生物化学修饰的透明质酸聚合物与可生物降解的纳米粒子混合后立即发生，并且由于强但可逆交联的动态性质，可以很容易地通过高规格注射器进行注射。此外，突出强调了通过附有 28-G 针头的长而窄的生理相关导管输送这种新型水凝胶的能力，输送后水凝胶的力学性能保持不变。由于凝胶的组成，证明可以通过不同的洗脱曲线来实现治疗药物的差异化释放，从而可以精确控制药物输送。最后，展示了这种创新水凝胶的细胞信号转导和生物相容性特性，揭示了其广泛的治疗应用。
