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纳米锶颗粒与重组人骨形态发生蛋白2的对比研究

An Comparison Study Between Strontium Nanoparticles and rhBMP2.

作者信息

Montagna Giulia, Cristofaro Francesco, Fassina Lorenzo, Bruni Giovanna, Cucca Lucia, Kochen Alejandro, Divieti Pajevic Paola, Bragdon Beth, Visai Livia, Gerstenfeld Louis

机构信息

Department of Molecular Medicine (DMM), Center for Health Technologies (CHT), UdR INSTM, University of Pavia, Pavia, Italy.

Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.

出版信息

Front Bioeng Biotechnol. 2020 Jun 16;8:499. doi: 10.3389/fbioe.2020.00499. eCollection 2020.

Abstract

The osteoinductive property of strontium was repeatedly proven in the last decades. Compelling data demonstrated that strontium hydroxyapatite nanoparticles exert a dual action, by promoting osteoblasts-driven matrix secretion and inhibiting osteoclasts-driven matrix resorption. Recombinant human bone morphogenetic protein 2 (rhBMP2) is a powerful osteoinductive biologic, used for the treatment of vertebral fractures and critically-sized bone defects. Although effective, the use of rhBMP2 has limitations due its recombinant morphogen nature. In this study, we examined the comparison between two osteoinductive agents: rhBMP2 and the innovative strontium-substituted hydroxyapatite nanoparticles. To test their effectiveness, we independently loaded Gelfoam sponges with the two osteoinductive agents and used the sponges as agent-carriers. Gelfoam are FDA-approved biodegradable medical devices used as delivery system for musculoskeletal defects. Their porous structure and spongy morphology make them attractive in orthopedic field. The abiotic characterization of the loaded sponges, involving ion release pattern and structure investigation, was followed by implantation onto the periosteum of healthy mice and comparison of the effects induced by each implant was performed. Abiotic analysis demonstrated that strontium was continuously released from the sponges over 28 days with a pattern similar to rhBMP2. Histological observations and gene expression analysis showed stronger endochondral ossification elicited by strontium compared to rhBMP2. Osteoclast activity was more inhibited by strontium than by rhBMP2. These results demonstrated the use of sponges loaded with strontium nanoparticles as potential bone grafts might provide better outcomes for complex fractures. Strontium nanoparticles are a novel and effective non-biologic treatment for bone injuries and can be used as novel powerful therapeutics for bone regeneration.

摘要

在过去几十年中,锶的骨诱导特性得到了反复验证。确凿的数据表明,羟基磷灰石锶纳米颗粒具有双重作用,既能促进成骨细胞驱动的基质分泌,又能抑制破骨细胞驱动的基质吸收。重组人骨形态发生蛋白2(rhBMP2)是一种强大的骨诱导生物制剂,用于治疗椎体骨折和临界尺寸的骨缺损。尽管rhBMP2有效,但由于其重组形态发生素的性质,其使用存在局限性。在本研究中,我们比较了两种骨诱导剂:rhBMP2和创新的锶取代羟基磷灰石纳米颗粒。为了测试它们的有效性,我们分别用这两种骨诱导剂加载明胶海绵,并将海绵用作药物载体。明胶海绵是美国食品药品监督管理局(FDA)批准的可生物降解医疗设备,用作肌肉骨骼缺损的递送系统。它们的多孔结构和海绵形态使其在骨科领域具有吸引力。对加载海绵的非生物特性进行表征,包括离子释放模式和结构研究,随后将其植入健康小鼠的骨膜上,并比较每种植入物诱导的效果。非生物分析表明,锶在28天内从海绵中持续释放,释放模式与rhBMP2相似。组织学观察和基因表达分析表明,与rhBMP2相比,锶诱导的软骨内成骨更强。锶对破骨细胞活性的抑制作用比rhBMP2更强。这些结果表明,使用负载锶纳米颗粒的海绵作为潜在的骨移植材料可能为复杂骨折提供更好的治疗效果。锶纳米颗粒是一种新型有效的非生物骨损伤治疗方法,可作为新型强大的骨再生治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc49/7308719/7903a1e4ac73/fbioe-08-00499-g0001.jpg

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