Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, 330-714, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 330-714, Republic of Korea.
Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, 330-714, Republic of Korea; Regenerative Medicine Research Institute, Universitat Internacional de Catalunya Barcelona 08017, Spain.
Biomaterials. 2018 Apr;162:183-199. doi: 10.1016/j.biomaterials.2018.02.005. Epub 2018 Feb 3.
Biomedical cements are considered promising injectable materials for bone repair and regeneration. Calcium phosphate composition sized with tens of micrometers is currently one of the major powder forms. Here we report a unique cement form made from mesoporous bioactive glass nanoparticles (BGn). The nanopowder could harden in reaction with aqueous solution at powder-to-liquid ratios as low as 0.4-0.5 (vs. 2.0-3.0 for conventional calcium phosphate cement CPC). The cementation mechanism investigated from TEM, XRD, FT-IR, XPS, and NMR analyses was demonstrated to be the ionic (Si and Ca) dissolution and then reprecipitation to form Si-Ca-(P) based amorphous nano-islands that could network the particles. The nanopowder-derived nanocement exhibited high surface area (78.7 m/g); approximately 9 times higher than conventional CPC. The immersion of nanocement in simulated body fluid produced apatite nanocrystallites with ultrafine size of 10 nm (vs. 55 nm in CPC). The ultrafine nanocement adsorbed protein molecules (particularly positive charged proteins) at substantial levels; approximately 160 times higher than CPC. The nanocement released Si and Ca ions continuously over the test period of 2 weeks; the Si release was unique in nanocement whereas the Ca release was in a similar range to that observed in CPC. The release of ions significantly stimulated the responses of cells studied (rMSCs and HUVECs). The viability and osteogenesis of rMSCs were significantly enhanced by the nanocement ionic extracts. Furthermore, the in vitro tubular networking of HUVECs was improved by the nanocement ionic extracts. The in vivo neo-blood vessel formation in CAM model was significantly higher by the nanocement implant when compared with the CPC counterpart, implying the Si ion release might play a significant role in pro-angiogenesis. Furthermore, the early bone forming response of the nanocement, based on the implantation in a rat calvarial bone defect, demonstrated a sign of osteoinductivity along with excellent osteocondution and bone matrix formation. Although more studies remain to confirm the potential of nanocement, some of the intriguing physico-chemical properties and the biological responses reported herein support the promise of the new 'nanopowder-based nanocement' for hard tissue repair and regeneration.
生物医学水泥被认为是有前途的可注射骨修复和再生材料。几十微米大小的磷酸钙组成目前是主要的粉末形式之一。在这里,我们报告了一种由介孔生物活性玻璃纳米粒子(BGn)制成的独特水泥形式。该纳米粉末可以在粉末与溶液的比例低至 0.4-0.5 时与水溶液反应硬化(而传统的磷酸钙水泥(CPC)为 2.0-3.0)。从 TEM、XRD、FT-IR、XPS 和 NMR 分析中研究的胶凝机制被证明是离子(Si 和 Ca)溶解,然后再沉淀形成 Si-Ca-(P)基无定形纳米岛,这些纳米岛可以使颗粒形成网络。由纳米粉末制成的纳米水泥表现出高比表面积(78.7 m/g);比传统 CPC 高约 9 倍。纳米水泥在模拟体液中的浸泡产生了超小尺寸为 10nm 的磷灰石纳米晶(而 CPC 中为 55nm)。超细纳米水泥吸附蛋白质分子(特别是带正电荷的蛋白质)的水平很高;比 CPC 高约 160 倍。纳米水泥在测试期 2 周内持续释放 Si 和 Ca 离子;Si 的释放在纳米水泥中是独特的,而 Ca 的释放与在 CPC 中观察到的相似。离子的释放显著刺激了所研究细胞(rMSCs 和 HUVECs)的反应。rMSCs 的活力和成骨能力因纳米水泥离子提取物而显著增强。此外,纳米水泥离子提取物促进了 HUVECs 的体外管状网络形成。与 CPC 相比,纳米水泥植入物在 CAM 模型中的新血管形成显著增加,这表明 Si 离子释放可能在促进血管生成中发挥重要作用。此外,基于大鼠颅顶骨缺损植入的纳米水泥的早期骨形成反应,表现出骨诱导活性以及出色的成骨和骨基质形成迹象。尽管还需要进一步的研究来证实纳米水泥的潜力,但本文报告的一些有趣的物理化学性质和生物学反应支持了新型“基于纳米粉末的纳米水泥”用于硬组织修复和再生的潜力。