Preparation of resorbable carbonate-substituted hollow hydroxyapatite microspheres and their evaluation in osseous defects in vivo.
Preparation of resorbable carbonate-substituted hollow hydroxyapatite microspheres and their evaluation in osseous defects in vivo.
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DOI：
10.1016/j.msec.2015.11.039
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Rahaman MN
中科院分区：
文献类型：
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作者：
Xiao W;Sonny Bal B;Rahaman MN
中空羟基磷灰石微球具有高比表面积的介孔结构，可作为蛋白质的生物活性和骨传导载体，促进骨再生。然而，合成HA具有缓慢的再吸收速率和有限的重塑成骨的能力。在本研究中，具有可控量的碳酸酯取代的中空HA微球（0-12 wt. %），并在体外和体内进行评价。中空HA微球具有约12 wt. %的碳酸盐（指定为CHA 12）显示出比常规中空HA微球（179 m2 g-1）更高的表面积（236 m2 g-1）和在乙酸钾缓冲溶液中更快的降解速率。当在大鼠颅骨缺损中植入12周时，CHA 12和HA微球显示出有限的骨再生能力，但CHA 12微球比HA微球吸收更快。用骨形态发生蛋白-2（BMP 2）（1 μg/缺损）加载微球刺激骨再生并加速CHA 12微球的再吸收。在12周时，植入CHA 12微球的缺损中的新骨的量（73 ± 8%）显著高于HA微球（59 ± 2%），而残留的CHA 12微球的量（总缺损面积的7 ± 2%）显著低于HA微球（21 ± 3%）。这些碳酸盐取代的HA微球与临床安全剂量的BMP 2的组合可以提供用于愈合非负载骨缺损的有前景的植入物。
Hollow hydroxyapatite (HA) microspheres, with a high-surface-area mesoporous shell, can provide a unique bioactive and osteoconductive carrier for proteins to stimulate bone regeneration. However, synthetic HA has a slow resorption rate and a limited ability to remodel into bone. In the present study, hollow HA microspheres with controllable amounts of carbonate substitution (0–12 wt. %) were created using a novel glass conversion route and evaluated in vitro and in vivo. Hollow HA microspheres with ~12 wt. % of carbonate (designated CHA12) showed a higher surface area (236 m2g−1) than conventional hollow HA microspheres (179 m2g−1) and a faster degradation rate in a potassium acetate buffer solution. When implanted for 12 weeks in rat calvarial defects, the CHA12 and HA microspheres showed a limited capacity to regenerate bone but the CHA12 microspheres resorbed faster than the HA microspheres. Loading the microspheres with bone morphogenetic protein-2 (BMP2) (1 μg per defect) stimulated bone regeneration and accelerated resorption of the CHA12 microspheres. At 12 weeks, the amount of new bone in the defects implanted with the CHA12 microspheres (73 ± 8 %) was significantly higher than the HA microspheres (59 ± 2%) while the amount of residual CHA12 microspheres (7 ± 2% of the total defect area) was significantly lower than the HA microspheres (21 ± 3%). The combination of these carbonate-substituted HA microspheres with clinically safe doses of BMP2 could provide promising implants for healing non-loaded bone defects.