1 Department of Orthopaedics, University Medical Center Utrecht , Utrecht, The Netherlands .
Tissue Eng Part A. 2013 Dec;19(23-24):2686-92. doi: 10.1089/ten.TEA.2012.0569. Epub 2013 Sep 11.
Bone regeneration is one of the focus points in the field of regenerative medicine. A well-known stimulus of bone formation is bone morphogenetic protein-2 (BMP-2), which has already been extensively used in clinical applications. However, due to a short half-life, supraphysiological doses are applied resulting in severe side effects such as ectopic bone formation or even loss of bone. We compared the effectivity of transient BMP-2 gene delivery with the BMP-2 protein at clinical (high) and physiological (low) doses by subcutaneous implantation of alginate-based constructs in mice. After 6 weeks of implantation, both the protein laden constructs and BMP-2 plasmid DNA-based constructs showed similar early bone onset and elevated bone formation compared to controls without any BMP-2 added. We found no differences in efficiency by using BMP-2 plasmid DNA or any of the BMP-2 protein dosages. Therefore, we conclude that BMP-2 plasmid DNA-based gene therapy in alginate is a promising new strategy for BMP-2 administration for bone (re)generation.
骨再生是再生医学领域的重点之一。骨形成的一种著名刺激物是骨形态发生蛋白-2（BMP-2），它已被广泛应用于临床应用。然而，由于半衰期短，应用超生理剂量会导致严重的副作用，如异位骨形成，甚至骨丢失。我们通过在小鼠皮下植入藻酸盐基构建物，比较了瞬时 BMP-2 基因传递与临床（高）和生理（低）剂量 BMP-2 蛋白的效果。植入 6 周后，与未添加任何 BMP-2 的对照组相比，负载蛋白质的构建物和 BMP-2 质粒 DNA 构建物均显示出类似的早期骨起始和升高的骨形成。使用 BMP-2 质粒 DNA 或任何 BMP-2 蛋白剂量均未发现效率差异。因此，我们得出结论，藻酸盐中基于 BMP-2 质粒 DNA 的基因治疗是 BMP-2 用于骨（再）生成的一种有前途的新策略。
