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用于骨再生的富锶可注射混合系统。

Strontium-rich injectable hybrid system for bone regeneration.

作者信息

Neves Nuno, Campos Bruno B, Almeida Isabel F, Costa Paulo C, Cabral Abel Trigo, Barbosa Mário A, Ribeiro Cristina C

机构信息

Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal; FMUP - Faculdade de Medicina da Universidade do Porto, Departamento de Cirurgia, Serviço de Ortopedia, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.

FCUP - Faculdade de Ciências da Universidade do Porto, Centro de Investigação em Química, Departamento de Química e Bioquímica, Rua do Campo Alegre 1021/1055, 4169-007 Porto, Portugal.

出版信息

Mater Sci Eng C Mater Biol Appl. 2016 Feb;59:818-827. doi: 10.1016/j.msec.2015.10.038. Epub 2015 Oct 23.

Abstract

Current challenges in the development of scaffolds for bone regeneration include the engineering of materials that can withstand normal dynamic physiological mechanical stresses exerted on the bone and provide a matrix capable of supporting cell migration and tissue ingrowth. The objective of the present work was to develop and characterize a hybrid polymer–ceramic injectable system that consists of an alginate matrix crosslinked in situ in the presence of strontium(Sr), incorporating a ceramic reinforcement in the form of Sr-rich microspheres. The incorporation of Sr in the microspheres and in the vehicle relies on the growing evidence that Sr has beneficial effects in bone remodeling and in the treatment of osteopenic disorders and osteoporosis. Sr-rich porous hydroxyapatite microspheres with a uniform size and a mean diameter of 555 μm were prepared, and their compression strength and friability tested. A 3.5% (w/v) ultrapure sodium alginate solution was used as the vehicle and its in situ gelation was promoted by the addition of calcium (Ca) or Sr carbonate and Glucone-δ-lactone. Gelation times varied with temperature and crosslinking agent, being slower for Sr than for Ca, but adequate for injection in both cases. Injectability was evaluated using a device employed in vertebroplasty surgical procedures, coupled to a texture analyzer in compression mode. Compositions with 35%w of microspheres presented the best compromise between injectability and compression strength of the system, the force required to extrude it being lower than 100 N.Micro CT analysis revealed a homogeneous distribution of the microspheres inside the vehicle, and a mean inter-microspheres space of 220 μm. DMA results showed that elastic behavior of the hybrid is over the viscous one and that the higher storage modulus was obtained for the 3.5%Alg–35%Sr-HAp-Sr formulation.

摘要

目前骨再生支架开发面临的挑战包括设计能够承受施加在骨骼上的正常动态生理机械应力并提供能够支持细胞迁移和组织长入的基质的材料。本研究的目的是开发并表征一种混合聚合物 - 陶瓷可注射系统,该系统由在锶(Sr)存在下原位交联的藻酸盐基质组成,并包含富锶微球形式的陶瓷增强材料。将Sr掺入微球和载体中是基于越来越多的证据表明Sr在骨重塑以及骨质疏松症和骨质减少症的治疗中具有有益作用。制备了尺寸均匀、平均直径为555μm的富Sr多孔羟基磷灰石微球,并测试了它们的抗压强度和易碎性。使用3.5%(w/v)的超纯海藻酸钠溶液作为载体,并通过添加钙(Ca)或碳酸锶和葡萄糖酸 - δ - 内酯促进其原位凝胶化。凝胶化时间随温度和交联剂而变化,Sr的凝胶化时间比Ca慢,但在两种情况下都足以进行注射。使用椎体成形术外科手术中使用的设备并结合压缩模式的纹理分析仪评估可注射性。含有35%w微球的组合物在系统的可注射性和抗压强度之间表现出最佳折衷,挤出所需的力低于100N。微型CT分析显示微球在载体内均匀分布,微球间平均间距为220μm。动态热机械分析(DMA)结果表明,该混合物的弹性行为超过粘性行为,并且对于3.5%藻酸盐 - 35%Sr - 羟基磷灰石 - Sr配方获得了更高的储能模量。

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