Departments of Orthopaedic Surgery, Stanford University, Stanford, CA 94305, USA.
Biomacromolecules. 2013 Mar 11;14(3):794-800. doi: 10.1021/bm3018559. Epub 2013 Feb 11.
Layer-by-layer (LBL) assembly is an attractive platform for controlled release of biologics given its mild fabrication process and versatility in coating substrates of any shape. Proteins can be incorporated into LBL coatings by sequentially depositing oppositely charged polyelectrolytes, which self-assemble into nanoscale films on medical devices or tissue engineering scaffolds. However, previously reported LBL platforms often require the use of a few hundred layers to avoid burst release, which hinders their broad translation due to the lengthy fabrication process, cost, and batch-to-batch variability. Here we report a biodegradable LBL platform composed of only 10 layers with tunable protein release kinetics, which is an order of magnitude less than previously reported LBL platforms. We performed a combinatorial study to examine the effects of polymer chemistry and order of deposition of poly(β-amino) esters on protein release kinetics under 81 LBL assembly conditions. Using the optimal "polyelectrolyte couples" for constructing the LBL film, basic fibroblast growth factor (bFGF) was released gradually over 14 days with retained biological activity to stimulate cell proliferation. The method reported herein is applicable for coating various substrates including metals, polymers, and ceramics and may be used for a broad range of biomedical and tissue engineering applications.
层层（LBL）组装是一种有吸引力的生物制剂控制释放平台，因为其制造工艺温和且通用性强，可以涂覆任何形状的基底。通过顺序沉积带相反电荷的聚电解质，可以将蛋白质掺入 LBL 涂层中，这些聚电解质在医疗器械或组织工程支架上自组装成纳米级薄膜。然而，以前报道的 LBL 平台通常需要使用几百层才能避免爆发式释放，由于制造过程漫长、成本高和批次间变异性，这阻碍了它们的广泛转化。在这里，我们报告了一种由仅 10 层组成的可生物降解的 LBL 平台，具有可调节的蛋白质释放动力学，这比以前报道的 LBL 平台少一个数量级。我们进行了组合研究，以检查聚（β-氨基）酯的聚合物化学和沉积顺序对 81 种 LBL 组装条件下蛋白质释放动力学的影响。在构建 LBL 膜时使用最佳的“聚电解质对”，碱性成纤维细胞生长因子（bFGF）在 14 天内逐渐释放，保持生物活性以刺激细胞增殖。本文报道的方法适用于涂覆各种基底，包括金属、聚合物和陶瓷，可用于广泛的生物医学和组织工程应用。
