Mahran Alaa, Howaili Fadak, Bhadane Rajendra, Mathiyalagan Rathna, Viitala Tapani, Wang Xiaoju, Rosenholm Jessica M
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland; Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt.
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland.
Eur J Pharm Sci. 2025 Aug 1;211:107132. doi: 10.1016/j.ejps.2025.107132. Epub 2025 May 18.
Three-dimensional (3D) printed hydrogel-based scaffolds have emerged as promising for the delivery of biologicals. Recently, we developed a printable plant-based nanocomposite hydrogel, composed of anionic cellulose nanofibers (T-CNF) and methacrylated galactoglucomannan (GGMMA), reinforced with mesoporous silica nanoparticles (MSNs) of different surface charges. However, ensuring the biological activity of the delivered biomolecules requires further investigation to validate the functionality of the developed biomaterial. To investigate this, in this study, horseradish peroxidase (HRP) and lysozyme were selected as distinct model proteins, assessing their immobilization stability and biological activity after MSN immobilization and 3D printing. The interactions between the enzymes and differently surface-modified MSNs were explored using multi-parametric surface plasmon resonance (MP-SPR) and molecular dynamics (MD) simulations. We observed that MSN surface charge is key to the extent of enzyme adsorption and activity control. Positively charged MSNs showed the highest HRP immobilization but caused significant activity loss in both enzymes. In contrast, near-neutral and negatively charged MSNs provided improved stability and activity retention for HRP and lysozyme, respectively. Except for lysozyme/hydrogel, HRP/hydrogel and enzyme-loaded nanocomposite hydrogels (HRP-loaded near-neutral and lysozyme-loaded negatively charged MSNs) were successfully 3D printed using different UV post-curing times. While enzyme-laden nanocomposite scaffolds showed promising immobilization stability, the presence of the photoinitiator caused significant inactivation for both enzymes. Irrespective of the crosslinking approach, this matrix demonstrates significant potential as a delivery carrier for various biomolecules, with promising applications in tissue engineering and wound healing.
基于三维（3D）打印水凝胶的支架已成为递送生物制剂的有前景的材料。最近，我们开发了一种可打印的植物基纳米复合水凝胶，它由阴离子纤维素纳米纤维（T-CNF）和甲基丙烯酸化半乳甘露聚糖（GGMMA）组成，并用不同表面电荷的介孔二氧化硅纳米颗粒（MSN）增强。然而，要确保所递送生物分子的生物活性，还需要进一步研究以验证所开发生物材料的功能。为了对此进行研究，在本研究中，选择辣根过氧化物酶（HRP）和溶菌酶作为不同的模型蛋白，评估它们在MSN固定化和3D打印后的固定稳定性和生物活性。使用多参数表面等离子体共振（MP-SPR）和分子动力学（MD）模拟探索了酶与不同表面修饰的MSN之间的相互作用。我们观察到MSN表面电荷是酶吸附程度和活性控制的关键。带正电荷的MSN显示出最高的HRP固定率，但导致两种酶的活性显著损失。相比之下，近中性和带负电荷的MSN分别为HRP和溶菌酶提供了更好的稳定性和活性保留。除了溶菌酶/水凝胶外，HRP/水凝胶和载酶纳米复合水凝胶（载有HRP的近中性和载有溶菌酶的带负电荷的MSN）使用不同的紫外后固化时间成功进行了3D打印。虽然载酶纳米复合支架显示出有前景的固定稳定性，但光引发剂的存在导致两种酶都发生了显著失活。无论交联方法如何，这种基质作为各种生物分子的递送载体都具有巨大潜力，在组织工程和伤口愈合方面有广阔的应用前景。
