<br>锶取代和雷奈酸锶负载羟基磷灰石纳米粒子的理化性质和体外生物相容性的比较研究,ACS Applied Bio Materials

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锶取代和雷奈酸锶负载羟基磷灰石纳米粒子的理化性质和体外生物相容性的比较研究
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2023-12-01 , DOI: 10.1021/acsabm.3c00539
Liga Stipniece _{1,

2} , Anna Ramata-Stunda ₃ , Jana Vecstaudza _{1,

2} , Inta Kreicberga _{1,

2} , Dora Livkisa ₃ , Anna Rubina _{1,

2} , Artemijs Sceglovs _{1,

2} , Kristine Salma-Ancane _{1,

2}

Affiliation

合成羟基磷灰石纳米粒子（nHAp）与骨矿物质具有相似的成分和结构，在骨再生医学中发挥着关键作用。用 Sr 对磷酸钙生物材料进行功能化， i 。骨细胞外基质微量元素，已被证明是一种有效的基于生物材料的体外和体内促进成骨的策略。用 Sr ²⁺离子或雷奈酸锶 (SrRAN) 功能化 nHAp 可以通过将生物活性分子局部递送到骨缺损微环境来提供有利的骨组织再生。此外，将抗骨质疏松药物 SrRAN 直接注射到特定部位的骨缺损中可以显着减少所需的药物剂量和可能的副作用的风险。我们的研究评估了用于通过湿沉淀功能化 nHAp 的 Sr 源（Sr ²⁺离子和 SrRAN）对其体外细胞活性的影响。对所开发的 Sr 功能化 nHAp 的理化性质、体外Sr ²⁺和 Ca ²⁺离子释放及其对体外细胞活性的影响进行了系统比较。 TRIS-HCl 中的离子释放测试表明，Sr 取代的 nHAp 和负载 SrRAN 的 HAp 中的 Sr ²⁺和 Ca ²⁺离子可在 21 天内缓慢且连续地释放。此外，在 DMEM 中评估了 SrRAN 和 Sr ²⁺离子释放动力学，以了解它们与同一时间范围内的体外细胞效应的相关性。 nHAp 中相对较低浓度（最高 2 wt%）的 Sr 导致前成骨细胞中碱性磷酸酶活性的增加以及成骨细胞中胶原蛋白 I 和骨钙素的表达，证明了它们促进骨形成的能力。

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A Comparative Study on Physicochemical Properties and In Vitro Biocompatibility of Sr-Substituted and Sr Ranelate-Loaded Hydroxyapatite Nanoparticles

Synthetic hydroxyapatite nanoparticles (nHAp) possess compositional and structural similarities to those of bone minerals and play a key role in bone regenerative medicine. Functionalization of calcium phosphate biomaterials with Sr, i.e., bone extracellular matrix trace element, has been proven to be an effective biomaterial-based strategy for promoting osteogenesis in vitro and in vivo. Functionalizing nHAp with Sr²⁺ ions or strontium ranelate (SrRAN) can provide favorable bone tissue regeneration by locally delivering bioactive molecules to the bone defect microenvironment. Moreover, administering an antiosteoporotic drug, SrRAN, directly into site-specific bone defects could significantly reduce the necessary drug dosage and the risk of possible side effects. Our study evaluated the impact of the Sr source (Sr²⁺ ions and SrRAN) used to functionalize nHAp by wet precipitation on its in vitro cellular activities. The systematic comparison of physicochemical properties, in vitro Sr²⁺ and Ca²⁺ ion release, and their effect on in vitro cellular activities of the developed Sr-functionalized nHAp was performed. The ion release tests in TRIS-HCl demonstrated a 21-day slow and continuous release of the Sr²⁺ and Ca²⁺ ions from both Sr-substituted nHAp and SrRAN-loaded HAp. Also, SrRAN and Sr²⁺ ion release kinetics were evaluated in DMEM to understand their correlation with in vitro cellular effects in the same time frame. Relatively low concentration (up to 2 wt %) of Sr in the nHAp led to an increase in the alkaline phosphatase activity in preosteoblasts and expression of collagen I and osteocalcin in osteoblasts, demonstrating their ability to boost bone formation.

更新日期：2023-12-01

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