A nano-hydroxyapatite - Pullulan/dextran polysaccharide composite macroporous material for bone tissue engineering
A nano-hydroxyapatite - Pullulan/dextran polysaccharide composite macroporous material for bone tissue engineering
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DOI：
10.1016/j.biomaterials.2013.01.049
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发表时间：
2013-04-01
期刊：
影响因子：
14
通讯作者：
Amedee, Joelle
中科院分区：
文献类型：
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作者：
Fricain, Jean Christophe;Schlaubitz, Silke;Amedee, Joelle
骨组织工程研究专注于开发能够刺激骨愈合的同种异体骨和自体骨移植替代物。在此，我们介绍了由天然亲水性多糖普鲁兰多糖和葡聚糖组成的支架，这些支架添加或未添加纳米晶羟基磷灰石颗粒（nHA）。体外研究表明，在缺乏骨诱导因子的培养基中，这些基质可诱导人骨髓基质细胞形成多细胞聚集体，并表达早期和晚期骨特异性标志物。在没有任何接种细胞的情况下，在小鼠和山羊体内进行异位植入实验，结果显示只有复合大孔支架（基质 + nHA）（i）能够在皮下保留局部生长因子，包括骨形态发生蛋白2（BMP2）和血管内皮生长因子165（VEGF165）；（ii）诱导生物磷灰石层的沉积；（iii）有利于在小鼠皮下形成致密的矿化组织，以及在山羊肌肉内植入后形成类骨质组织。此后，将复合支架植入不同大小动物的临界尺寸骨缺损的正位临床前模型中，植入部位包括三个不同的骨骼部位，即大鼠股骨髁、山羊横向下颌骨缺损和胫骨截骨部位。无论植入部位如何，基质nHA在这三个模型中都能诱导形成高度矿化的组织，以及在与基质直接接触处形成类骨质组织和骨组织再生。因此，我们提出这种复合基质可作为一种材料，用于刺激宿主间充质干细胞向骨细胞分化以及在骨科和颌面外科应用中促进骨形成。（C）2013爱思唯尔有限公司。保留所有权利。
Research in bone tissue engineering is focused on the development of alternatives to allogenic and autologous bone grafts that can stimulate bone healing. Here, we present scaffolds composed of the natural hydrophilic polysaccharides pullulan and dextran, supplemented or not with nanocrystalline hydroxyapatite particles (nHA). In vitro studies revealed that these matrices induced the formation of multicellular aggregates and expression of early and late bone specific markers with human bone marrow stromal cells in medium deprived of osteoinductive factors. In absence of any seeded cells, heterotopic implantation in mice and goat, revealed that only the composite macroporous scaffold (Matrix + nHA) (i) retained subcutaneously local growth factors, including Bone Morphogenetic Protein 2 (BMP2) and VEGF165, (ii) induced the deposition of a biological apatite layer, (iii) favored the formation of a dense mineralized tissue subcutaneously in mice, as well osteoid tissue after intramuscular implantation in goat. The composite scaffold was thereafter implanted in orthotopic preclinical models of critical size defects, in small and large animals, in three different bony sites, i.e. the femoral condyle of rat, a transversal mandibular defect and a tibial osteotomy in goat. The Matrix nHA induced a highly mineralized tissue in the three models whatever the site of implantation, as well as osteoid tissue and bone tissue regeneration in direct contact to the matrix. We therefore propose this composite matrix as a material for stimulating bone cell differentiation of host mesenchymal stem cells and bone formation for orthopedic and maxillofacial surgical applications. (C) 2013 Elsevier Ltd. All rights reserved.