To guide the natural bone regeneration process, bone tissue engineering strategies rely on the development of a scaffold architecture that mimics the extracellular matrix and incorporates important extracellular signaling molecules, which promote fracture healing and bone formation pathways. Incorporation of growth factors into particles embedded within the scaffold can offer both protection of protein bioactivity and a sustained release profile. In this work, a novel method to immobilize carrier nanoparticles within scaffold pores is proposed. A biodegradable, osteoconductive, porous chitosan scaffold was fabricated via the “freeze‐drying method,” leading to scaffolds with a storage modulus of 8.5 kPa and 300 μm pores, in line with existing bone scaffold properties. Next, poly(methyl methacrylate‐co‐methacrylic acid) nanoparticles were synthesized and immobilized to the scaffold via carbodiimide‐crosslinker chemistry. A fluorescent imaging study confirmed that the conventional methods of protein and nanocarrier incorporation into scaffolds can lead to over 60% diffusion out of the scaffold within the first 5 min of implantation, and total disappearance within 4 weeks. The novel method of nanocarrier immobilization to the scaffold backbone via carbodiimide‐crosslinker chemistry allows full retention of particles for up to 4 weeks within the scaffold bulk, with no negative effects on the viability and proliferation of human umbilical vein endothelial cells.

中文翻译：

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将纳米载体固定在多孔壳聚糖支架内，用于在骨组织工程应用中持续递送生长因子。

为了指导自然骨再生过程，骨组织工程策略依赖于模拟细胞外基质并结合重要的细胞外信号分子的支架结构的发展，这些分子促进骨折愈合和骨形成途径。将生长因子掺入嵌入支架内的颗粒中可以提供蛋白质生物活性的保护和缓释曲线。在这项工作中，提出了一种将载体纳米颗粒固定在支架孔内的新方法。通过“冷冻干燥法”制造了一种可生物降解、骨传导性、多孔壳聚糖支架，其储能模量为 8.5 kPa，孔隙为 300 μm，与现有的骨支架特性一致。下一个，聚（甲基丙烯酸甲酯-共聚-甲基丙烯酸）纳米粒子被合成并通过碳二亚胺-交联剂化学固定在支架上。一项荧光成像研究证实，将蛋白质和纳米载体掺入支架的传统方法可导致在植入的前 5 分钟内超过 60% 的扩散从支架中扩散出来，并在 4 周内完全消失。通过碳二亚胺-交联剂化学将纳米载体固定到支架骨架的新方法可以将颗粒完全保留在支架本体中长达 4 周，对人脐静脉内皮细胞的活力和增殖没有负面影响。一项荧光成像研究证实，将蛋白质和纳米载体掺入支架的常规方法可导致在植入的前 5 分钟内超过 60% 的扩散从支架中扩散出来，并在 4 周内完全消失。通过碳二亚胺-交联剂化学将纳米载体固定到支架骨架的新方法可以将颗粒完全保留在支架本体中长达 4 周，对人脐静脉内皮细胞的活力和增殖没有负面影响。一项荧光成像研究证实，将蛋白质和纳米载体掺入支架的常规方法可导致在植入的前 5 分钟内超过 60% 的扩散从支架中扩散出来，并在 4 周内完全消失。通过碳二亚胺-交联剂化学将纳米载体固定到支架骨架的新方法可以将颗粒完全保留在支架本体中长达 4 周，对人脐静脉内皮细胞的活力和增殖没有负面影响。