Poldervaart Michelle T, Wang Huanan, van der Stok Johan, Weinans Harrie, Leeuwenburgh Sander C G, Öner F Cumhur, Dhert Wouter J A, Alblas Jacqueline
Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands.
PLoS One. 2013 Aug 19;8(8):e72610. doi: 10.1371/journal.pone.0072610. eCollection 2013.
The design of bioactive three-dimensional (3D) scaffolds is a major focus in bone tissue engineering. Incorporation of growth factors into bioprinted scaffolds offers many new possibilities regarding both biological and architectural properties of the scaffolds. This study investigates whether the sustained release of bone morphogenetic protein 2 (BMP-2) influences osteogenicity of tissue engineered bioprinted constructs. BMP-2 loaded on gelatin microparticles (GMPs) was used as a sustained release system, which was dispersed in hydrogel-based constructs and compared to direct inclusion of BMP-2 in alginate or control GMPs. The constructs were supplemented with goat multipotent stromal cells (gMSCs) and biphasic calcium phosphate to study osteogenic differentiation and bone formation respectively. BMP-2 release kinetics and bioactivity showed continuous release for three weeks coinciding with osteogenicity. Osteogenic differentiation and bone formation of bioprinted GMP containing constructs were investigated after subcutaneous implantation in mice or rats. BMP-2 significantly increased bone formation, which was not influenced by the release timing. We showed that 3D printing of controlled release particles is feasible and that the released BMP-2 directs osteogenic differentiation in vitro and in vivo.
生物活性三维（3D）支架的设计是骨组织工程的主要研究重点。将生长因子整合到生物打印支架中，为支架的生物学和结构特性提供了许多新的可能性。本研究调查骨形态发生蛋白2（BMP-2）的持续释放是否会影响组织工程生物打印构建体的成骨性。负载在明胶微粒（GMPs）上的BMP-2被用作持续释放系统，该系统分散在基于水凝胶的构建体中，并与将BMP-2直接包埋在藻酸盐中或对照GMPs进行比较。构建体分别添加山羊多能间充质细胞（gMSCs）和双相磷酸钙，以研究成骨分化和骨形成。BMP-2的释放动力学和生物活性显示持续释放三周，与成骨性一致。在小鼠或大鼠皮下植入后，研究了含生物打印GMP构建体的成骨分化和骨形成。BMP-2显著增加骨形成，这不受释放时间的影响。我们表明，控释颗粒的3D打印是可行的，并且释放的BMP-2在体外和体内均能引导成骨分化。
