Salcedo-Abraira Pablo, Fernández-Grajera María, Guerrero-Román Francisco A, Rodríguez-Diéguez Antonio, Luque-Agudo Veronica, González-Martín María Luisa, Gallardo-Moreno Amparo M, Rojas Sara
Department of Inorganic Chemistry, University of Granada, Avda. Fuente nueva s/n, 18071 Granada, Spain.
Center for Networked Biomedical Research on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Badajoz 06006, Spain.
Cryst Growth Des. 2025 Feb 20;25(5):1415-1422. doi: 10.1021/acs.cgd.4c01478. eCollection 2025 Mar 5.
Metal-organic frameworks (MOFs) can be prepared from bioactive molecules, which are released during the degradation of the material in the body. Particularly, MOFs have recently emerged as bisphosphonate (BP) drug delivery systems. In this work, two novel MOFs based on the smallest bisphosphonate medronic acid (MA) and calcium with formulas [Ca-(CHOP)·HO] (GR-MOF-23) and [Ca-(CHOP)·CHOH] (GR-MOF-24) in aqueous and/or methanolic solutions at room temperature were synthesized and fully characterized. The stability test performed in simulated physiological conditions (a phosphate buffer saline (PBS, pH = 7.4, 10 mM) solution at 37 °C) showed a progressive Ca leaching from both GR-MOF-23 and GR-MOF-24, achieving 38.0 ± 2.8 and 35.8 ± 3.9% release of calcium after 1 week of suspension. Interestingly, the recovered solid residues from the stability tests were identified as apatite and calcium phosphate phases, which might facilitate the formation of bone apatite and collagen. The antibacterial activity of GR-MOF-23 and GR-MOF-24 was investigated against Escherichia coli and Staphylococcus aureus, among the most relevant human pathogens, causing a wide variety of infections in bone fracture in osteoporosis and prosthesis. While both materials exhibited bacteria growth inhibition, GR-MOF-24 also showed a bactericide action, likely due to a more progressive release of Ca, which is the ion related to the improved stability of the biofilm. These innovative materials present exciting opportunities for developing antibacterial surfaces in prosthetics and the treatment of bone fracture infections.
金属有机框架（MOFs）可由生物活性分子制备，这些生物活性分子在材料于体内降解过程中释放出来。特别地，MOFs最近已成为双膦酸盐（BP）药物递送系统。在本工作中，在室温下于水性和/或甲醇溶液中合成了两种基于最小双膦酸盐美罗昔康酸（MA）和钙的新型MOFs，其化学式分别为[Ca-(CHOP)·HO]（GR-MOF-23）和[Ca-(CHOP)·CHOH]（GR-MOF-24），并对其进行了全面表征。在模拟生理条件（37℃下的磷酸盐缓冲盐水（PBS，pH = 7.4，10 mM）溶液）中进行的稳定性测试表明，GR-MOF-23和GR-MOF-24均有钙的逐步浸出，悬浮1周后钙的释放量分别达到38.0±2.8%和35.8±3.9%。有趣的是，稳定性测试中回收的固体残留物被鉴定为磷灰石和磷酸钙相，这可能有助于骨磷灰石和胶原蛋白的形成。研究了GR-MOF-23和GR-MOF-24对大肠杆菌和金黄色葡萄球菌的抗菌活性，这两种菌是最相关的人类病原体，可在骨质疏松症骨折和假体中引起多种感染。虽然两种材料都表现出细菌生长抑制作用，但GR-MOF-24还表现出杀菌作用，这可能是由于钙的释放更为渐进，而钙是与生物膜稳定性提高相关的离子。这些创新材料为开发用于假体的抗菌表面和治疗骨折感染提供了令人兴奋的机会。
