Sedaghat Alireza, Shokrolahi Fatemeh, Yeganeh Hamid, Shokrollahi Parvin, Hosseini Samaneh
Department of Biomaterials, Faculty of Science, Iran Polymer and Petrochemical Institute, Tehran, Iran.
Department of Biomaterials, Faculty of Science, Iran Polymer and Petrochemical Institute, Tehran, Iran.
Int J Biol Macromol. 2025 Sep;321(Pt 1):146092. doi: 10.1016/j.ijbiomac.2025.146092. Epub 2025 Jul 17.
Injectable Gellan Gum-Gelatin hydrogel (GG/gelatin hydrogel) with PLGA-LDH composite microspheres (Gel-PMA) was developed for controlled alendronate (ALN) release and enhanced bone regeneration. Manganese-Zinc Layered Double Hydroxide (LDH) nanoparticles (∼142 nm) were synthesized, loaded with ALN (ALN-LDH, about 25 %), and encapsulated in poly (d,l-lactide-co-glycolide) (PLGA) microspheres (∼120 μm) via a solid-in-oil-in-water (S/O/W) double-emulsion technique. Microspheres (10 wt%) were incorporated into a GG/gelatin hydrogel and crosslinked with CaCl₂. Physicochemical and morphological analyses confirmed successful fabrication of LDH, ALN-LDH, ALN-LDH-loaded PLGA microspheres, and composite hydrogels. Mechanical testing showed that incorporating PLGA microspheres increased compressive strength from 30 to 170 kPa. Gel-PMA enabled sustained ALN release (∼95 % in 28 days), significantly improving ALN cumulative released amount (drug availability) over previous studies. Gel-PMA also exhibited excellent biocompatibility (>90 % cell viability). In vitro studies demonstrated osteogenic potential of Gel-PMA through increased ALP activity (0.0062 to 0.022 μmol/min/mg), calcium deposition (0.0125 to 0.022 μg/μl), and Alizarin Red staining over 28 days. ARS and MT assays, alongside upregulated ALP, Col I, and OCN gene expression, further confirmed osteogenic differentiation. These findings highlight Gel-PMA as a promising injectable scaffold for bone tissue engineering, offering controlled drug release, enhanced mechanical properties, and superior osteogenic potential.
开发了一种含有聚乳酸-羟基乙酸共聚物-层状双氢氧化物（PLGA-LDH）复合微球的可注射结冷胶-明胶水凝胶（GG/明胶水凝胶）（Gel-PMA），用于阿仑膦酸盐（ALN）的控释和增强骨再生。合成了锰锌层状双氢氧化物（LDH）纳米颗粒（约142纳米），负载ALN（ALN-LDH，约25%），并通过水包油包水（S/O/W）双乳液技术封装在聚（d，l-丙交酯-共-乙交酯）（PLGA）微球（约120微米）中。将微球（10重量%）掺入GG/明胶水凝胶中，并用CaCl₂交联。物理化学和形态分析证实成功制备了LDH、ALN-LDH、负载ALN-LDH的PLGA微球和复合水凝胶。力学测试表明，掺入PLGA微球使抗压强度从30 kPa提高到170 kPa。Gel-PMA能够实现ALN的持续释放（28天内约95%），与以往研究相比，显著提高了ALN的累积释放量（药物利用率）。Gel-PMA还表现出优异的生物相容性（细胞活力>90%）。体外研究通过在28天内增加碱性磷酸酶（ALP）活性（从0.0062至0.022微摩尔/分钟/毫克）、钙沉积（从0.0125至0.022微克/微升）和茜素红染色，证明了Gel-PMA的成骨潜力。茜素红染色（ARS）和甲基噻唑啉酮（MT）测定，以及上调的ALP、I型胶原（Col I）和骨钙素（OCN）基因表达，进一步证实了成骨分化。这些发现突出了Gel-PMA作为一种有前景的用于骨组织工程的可注射支架，具有控释药物、增强的力学性能和优异的成骨潜力。
