Tissue integration of growth factor-eluting layer-by-layer polyelectrolyte multilayer coated implants.
Tissue integration of growth factor-eluting layer-by-layer polyelectrolyte multilayer coated implants.
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DOI：
10.1016/j.biomaterials.2010.10.052
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发表时间：
2011-02
期刊：
影响因子：
14
通讯作者：
Hammond, Paula T.
中科院分区：
文献类型：
--
作者：
Macdonald, Mara L.;Samuel, Raymond E.;Shah, Nisarg J.;Padera, Robert F.;Beben, Yvette M.;Hammond, Paula T.
关键词：
药物洗脱涂层可以引导宿主组织对植入医疗器械的反应，有可能减轻植入并发症的医疗和经济负担。然而，由于在该竞技场中有用的许多药物在本质上是生物的，因此生物制剂（包括生长因子）的递送策略的缺乏目前限制了可以对植入环境施加的控制。层层（LbL）的多层膜是非常有吸引力的生物水库，由于保形涂层的困难的几何形状，水处理可能会保留脆弱的蛋白质功能，和可持续性的掺入和释放曲线。在此，我们描述了第一个LbL膜能够微克级释放的生物骨形态发生蛋白2（BMP-2），这是能够指导宿主组织的反应，从天然祖细胞产生骨。在体外两周的时间内释放10微克的BMP-2;在前3小时内释放不到1%（与商业胶原基质相比，商业胶原基质可以释放高达60%的BMP-2，太快而不能诱导分化）。从LbL膜释放的BMP-2保留了其在MC 3 T3 E1 S4前成骨细胞中诱导骨分化的能力，如通过碱性磷酸酶的诱导和钙染色（通过茜素红）和钙基质染色（通过Von Kossa）所测量的。在体内，将BMP-2膜涂覆的支架与缺乏BMP-2的膜涂覆的支架进行比较。肌内植入的BMP-2涂层能够启动宿主祖细胞分化成骨，通过MicroCT和组织学测量，骨在4至9周内成熟并扩增。这种LbL膜代表了控制和调节宿主对植入医疗器械的反应的新步骤，这可能最终增加植入器械的成功率，为骨伤口愈合提供替代的新方法，并为开发多治疗释放涂层奠定基础。
Drug eluting coatings that can direct the host tissue response to implanted medical devices have the potential to ameliorate both the medical and financial burden of complications from implantation. However, because many drugs useful in this arena are biologic in nature, a paucity of delivery strategies for biologics, including growth factors, currently limits the control that can be exerted on the implantation environment. Layer-by-Layer (LbL) polyelectrolyte multilayer films are highly attractive as ultrathin biologic reservoirs, due to conformal coating of difficult geometries, aqueous processing likely to preserve fragile protein function, and tenability of incorporation and release profiles. Herein, we describe the first LbL films capable of microgram-scale release of the biologic Bone Morphogenetic Protein 2 (BMP-2), which is capable of directing the host tissue response to create bone from native progenitor cells. Ten micrograms of BMP-2 are released over a period of two weeks in vitro; less than 1% is released in the first 3 hours (compared with commercial collagen matrices which can release up to 60% of BMP-2, too quickly to induce differentiation). BMP-2 released from LbL films retains its ability to induce bone differentiation in MC3T3 E1S4 preosteoblasts, as measured by induction of alkaline phosphatase and stains for calcium (via Alizarin Red) and calcium matrix (via Von Kossa). In vivo, BMP-2 film coated scaffolds were compared with film coated scaffolds lacking BMP-2. BMP-2 coatings implanted intramuscularly were able to initiate host progenitor cells to differentiate into bone, which matured and expanded from four to nine weeks as measured by MicroCT and histology. Such LbL films represent new steps towards controlling and tuning host response to implanted medical devices, which may ultimately increase the success of implanted devices, provide alternative new approaches toward bone wound healing, and lay the foundation for development of a multi-therapeutic release coating.
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DOI：
10.1016/j.jconrel.2008.07.032
发表时间：
2008-11-12
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Macdonald M;Rodriguez NM;Smith R;Hammond PT
通讯作者：
Hammond PT
影响因子：
5.5
作者：
Lavalle, P;Gergely, C;Picart, C
通讯作者：
Picart, C
DOI：
10.1073/pnas.0602884103
发表时间：
2006-07-05
影响因子：
11.1
作者：
Wood, Kris C.;Chuang, Helen F.;Hammond, Paula T.
通讯作者：
Hammond, Paula T.
影响因子：
8.6
作者：
Smith, Renee C.;Leung, Amy;Hammond, Paula T.
通讯作者：
Hammond, Paula T.
影响因子：
3.9
作者：
Porcel, C;Lavalle, P;Schaaf, P
通讯作者：
Schaaf, P