Hybrid Shear-thinning Hydrogel Integrating Hyaluronic Acid with ROS-Responsive Nanoparticles.
Hybrid Shear-thinning Hydrogel Integrating Hyaluronic Acid with ROS-Responsive Nanoparticles.
复制标题
将透明质酸与 ROS 响应纳米颗粒结合在一起的混合剪切稀化水凝胶。
DOI：
10.1002/adfm.202213368
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发表时间：
2023
影响因子：
19
通讯作者：
Gupta,MukeshK
中科院分区：
文献类型：
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作者：
Bezold,MariahG;Hanna,AndrewR;Dollinger,BryanR;Patil,Prarthana;Yu,Fang;Duvall,CraigL;Gupta,MukeshK
纳米粒子（NP）超组装提供了独特的机会来调整宏观水凝胶的机械强度、材料降解和药物递送特性。在这里，合成的活性氧（ROS）响应性NP通过客体-主体化学与透明质酸（HA）物理交联以产生剪切稀化NP/HA水凝胶。合成了具有不同三嵌段结构和金刚烷接枝密度的聚（丙烯硫醚）-B-聚（N，N-二甲基丙烯酰胺）-B-聚（N，N-二甲基丙烯酰胺-co-N-（1-金刚烷基）丙烯酰胺）三嵌段共聚物库，然后自组装成表面显示金刚烷的纳米粒子。将自组装的NP与β-环糊精接枝的HA混合以产生十八种NP/HA水凝胶制剂。NP/HA水凝胶平台显示出比仅含HA的水凝胶具有上级机械强度、对氧化/酶降解的敏感性以及固有的细胞保护和抗氧化功能。NP/HA水凝胶的性能被证明是受三嵌段结构，客体/主体接枝密度，和HA组合物。特别是，自组装NP的亲水性第二嵌段的长度和金刚烷接枝密度显著影响水凝胶的机械性能和剪切变稀行为，而聚（丙烯硫醚）的ROS反应性保护细胞免受细胞毒性ROS的影响，并与仅HA的水凝胶相比减少HA的氧化降解。这项研究为设计混合NP/HA水凝胶提供了聚合物结构-功能考虑因素，并确定了抗氧化剂，剪切稀化水凝胶作为小分子药物和治疗细胞的有前途的可注射递送平台。
Nanoparticle (NP) supra‐assembly offers unique opportunities to tune macroscopic hydrogels’ mechanical strength, material degradation, and drug delivery properties. Here, synthetic, reactive oxygen species (ROS)‐responsive NPs are physically cross‐linked with hyaluronic acid (HA) through guest‐host chemistry to create shear‐thinning NP/HA hydrogels. A library of triblock copolymers composed of poly(propylene sulfide)‐b‐poly(N,N‐dimethylacrylamide)‐b‐poly(N,N‐dimethylacrylamide‐co‐N‐(1‐adamantyl)acrylamide) are synthesized with varied triblock architectures and adamantane grafting densities and then self‐assembled into NPs displaying adamantane on their surface. Self‐assembled NPs are mixed with β‐cyclodextrin grafted HA to yield eighteen NP/HA hydrogel formulations. The NP/HA hydrogel platform demonstrates superior mechanical strength to HA‐only hydrogels, susceptibility to oxidative/enzymatic degradation, and inherent cell‐protective, antioxidant function. The performance of NP/HA hydrogels is shown to be affected by triblock architecture, guest/host grafting densities, and HA composition. In particular, the length of the hydrophilic second block and adamantane grafting density of self‐assembled NPs significantly impacts hydrogel mechanical properties and shear‐thinning behavior, while ROS‐reactivity of poly(propylene sulfide) protects cells from cytotoxic ROS and reduces oxidative degradation of HA compared to HA‐only hydrogels. This study provides insight into polymer structure‐function considerations for designing hybrid NP/HA hydrogels and identifies antioxidant, shear‐thinning hydrogels as promising injectable delivery platforms for small molecule drugs and therapeutic cells.