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负载 BMP-2 的 TCP/HAP 多孔陶瓷的性能与聚电解质多层膜涂层。

The performance of BMP-2 loaded TCP/HAP porous ceramics with a polyelectrolyte multilayer film coating.

机构信息

LMGP, UMR 5628 CNRS/INPG, 3 parvis Louis Néel, 38016 Grenoble, France.

出版信息

Biomaterials. 2011 Oct;32(30):7543-54. doi: 10.1016/j.biomaterials.2011.06.062. Epub 2011 Jul 23.

DOI:10.1016/j.biomaterials.2011.06.062
PMID:21783243
Abstract

Delivering rhBMP-2 (recombinant Bone Morphogenic Protein-2) at low but therapeutically efficient dose is one of the current challenges for bone tissue repair. In this context, Polyelectrolyte Multilayer films (PEM) represent an attractive rhBMP-2 carrier due to their ability to protect proteins from denaturation and to coat a wide variety of materials with complex geometry. Herein, we coated macroporous TCP/HAP granules with a biopolymeric PEM film to deliver rhBMP-2 in a "matrix-bound" manner. In vitro release kinetics indicated that the PEM-coated granules sequestered significant amounts of rhBMP-2. The degree of film cross-linking influenced the quantity of rhBMP-2 trapped within the films. Bare (uncoated) TCP/HAP scaffolds were also able to retain rhBMP-2. Bioactivity of rhBMP-2 in the PEM-coated granules was confirmed on two cell markers: luciferase expression on BMP-responsive-element/Luc C2C12 cells and alkaline phosphatase activity induction on C2C12 cells. Promisingly, rhBMP-2 adsorbed onto PEM-coated and on bare granules in a lesser extent, could be stored and remained bioactive over at least 3 weeks. In vivo, both uncoated and PEM-coated TCP/HAP granules loaded with rhBMP-2 exhibited both osteoconductive and osteoinductive properties. This opens perspective for coating these bioactive PEM on other types of implantable materials, including metal alloy that do not exhibit any affinity for rhBMP-2.

摘要

以低但治疗有效的剂量递送 rhBMP-2(重组骨形态发生蛋白-2)是骨组织修复的当前挑战之一。在这种情况下,聚电解质多层膜(PEM)由于其保护蛋白质变性和用复杂几何形状涂覆各种材料的能力,代表了 rhBMP-2 的有吸引力的载体。在此,我们用生物聚合物 PEM 膜涂覆大孔 TCP/HAP 颗粒,以“基质结合”的方式递送 rhBMP-2。体外释放动力学表明,PEM 涂层颗粒隔离了大量 rhBMP-2。膜交联的程度影响了被困在膜内的 rhBMP-2 的量。裸(未涂层)TCP/HAP 支架也能够保留 rhBMP-2。rhBMP-2 在 PEM 涂层颗粒中的生物活性通过两个细胞标志物得到证实:BMP 反应元件/Luc C2C12 细胞上的荧光素酶表达和 C2C12 细胞上碱性磷酸酶活性诱导。有希望的是,吸附在 PEM 涂层和裸颗粒上的 rhBMP-2 可以储存并保持生物活性至少 3 周。在体内,负载 rhBMP-2 的未涂层和 PEM 涂层 TCP/HAP 颗粒均表现出骨诱导和骨诱导特性。这为在其他类型的可植入材料(包括不表现出对 rhBMP-2 的任何亲和力的金属合金)上涂覆这些生物活性 PEM 开辟了前景。

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