Ripamonti Ugo, Crooks Jean, Khoali Lerato, Roden Laura
Bone Research Unit, Medical Research Council at the University of the Witwatersrand, Johannesburg, Medical School, 2193 Parktown, South Africa.
Biomaterials. 2009 Mar;30(7):1428-39. doi: 10.1016/j.biomaterials.2008.10.065. Epub 2008 Dec 9.
The spontaneous induction of bone formation in heterotopic rectus abdominis and orthotopic calvarial sites by coral-derived biomimetic matrices of different chemical compositions was investigated in a long-term study in the non-human primate Papio ursinus. Coral-derived calcium carbonate constructs were converted to hydroxyapatite by hydrothermal exchange. Limited conversion produced hydroxyapatite/calcium carbonate (HA/CC) constructs of 5% and 13% hydroxyapatite. Rods of 20 mm in length and 7 mm in diameter were implanted in heterotopic rectus abdominis sites; discs 25 mm in diameter were implanted in orthotopic calvarial defects of six adult non-human primates P. ursinus. Heterotopic samples also included fully converted hydroxyapatite replicas sintered at 1100 degrees C. To further enhance spontaneous osteoinductive activity, fully converted hydroxyapatite replicas were coated with the synthetic peptide P15 known to increase the adhesion of fibroblasts to anorganic bovine mineral. Bone induction was assessed at 60, 90 and 365 days by histological examination, alkaline phosphatase and osteocalcin expression, as well as by the expression of BMP-7, GDF-10 and collagen type IV mRNAs. Induction of bone occurred in the concavities of the matrices at all time points. At 365 days, bone marrow was evident in the P15-coated and uncoated implants. Resorption of partially converted calcium carbonate/hydroxyapatite was apparent, as well as remodeling of the newly formed bone. Northern blot analyses of samples from heterotopic specimens showed high levels of expression of BMP-7 and collagen type IV mRNA in all specimen types at 60 days, correlating with the induction of the osteoblastic phenotype in invading fibrovascular cells. Orthotopic specimens showed prominent bone formation across the different implanted constructs. The concavities of the matrices biomimetize the remodeling cycle of the osteonic primate cortico-cancellous bone and promote the ripple-like cascade of the induction of bone formation. This study demonstrates for the first time that partially converted HA/CC constructs also induce spontaneous differentiation of bone, albeit only seen one year post-implantation.
在一项针对南非狒狒（Papio ursinus）的长期研究中，研究了不同化学成分的珊瑚衍生仿生基质在异位腹直肌和原位颅骨部位自发诱导骨形成的情况。通过水热交换将珊瑚衍生的碳酸钙构建体转化为羟基磷灰石。有限的转化产生了含5%和13%羟基磷灰石的羟基磷灰石/碳酸钙（HA/CC）构建体。将长度为20毫米、直径为7毫米的棒植入异位腹直肌部位；将直径为25毫米的圆盘植入六只成年南非狒狒的原位颅骨缺损处。异位样本还包括在1100摄氏度下烧结的完全转化的羟基磷灰石复制品。为了进一步增强自发骨诱导活性，将完全转化的羟基磷灰石复制品用已知可增加成纤维细胞与无机牛矿物质粘附的合成肽P15进行包被。在60天、90天和365天时，通过组织学检查、碱性磷酸酶和骨钙素表达以及BMP - 7、GDF - 10和IV型胶原mRNA的表达来评估骨诱导情况。在所有时间点，骨诱导均发生在基质的凹处。在365天时，在P15包被和未包被的植入物中均可见明显的骨髓。部分转化的碳酸钙/羟基磷灰石的吸收明显，新形成的骨也在重塑。对异位标本样本的Northern印迹分析显示，在60天时，所有标本类型中BMP - 7和IV型胶原mRNA的表达水平都很高，这与侵袭性纤维血管细胞中骨细胞表型的诱导相关。原位标本在不同植入构建体中均显示出显著的骨形成。基质的凹处模拟了灵长类骨皮质 - 松质骨的重塑周期，并促进了骨形成诱导的涟漪状级联反应。这项研究首次证明，部分转化的HA/CC构建体也能诱导骨的自发分化，尽管仅在植入后一年才观察到。
