Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, Charitéplatz 1, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin Brandenburg School for Regenerative Therapies, Föhrer Str. 15, 13353 Berlin, Germany; German Rheumatism Research Centre (DRFZ) Berlin, A Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin Brandenburg Center for Regenerative Therapies, Föhrer Str. 15, 13353 Berlin, Germany.
Max Delbrück Center for Molecular Medicine, BIH Core Facility Proteomics, Robert-Rössle-Str 10, 13125 Berlin, Germany.
Acta Biomater. 2019 Mar 1;86:171-184. doi: 10.1016/j.actbio.2018.12.043. Epub 2019 Jan 5.
Although several biomaterials for bone regeneration have been developed in the last decades, clinical application of bone morphogenetic protein 2 is clinically only approved when applied on an absorbable bovine collagen I scaffold (ACS) (Helistat; ACS-H). In research, another ACS, namely Lyostypt (ACS-L) is frequently used as a scaffold in bone-linked studies. Nevertheless, until today, the influence of ACS alone on bone healing remains unknown. Unexpectedly, in vitro studies using ASC-H revealed a suppression of osteogenic differentiation and a significant reduction of cell vitality when compared to ASC-L. In mice, we observed a significant delay in bone healing when applying ACS-L in the fracture gap during femoral osteotomy. The results of our study show for the first time a negative influence of both ACS-H and ACS-L on bone formation demonstrating a substantial need for more sophisticated delivery systems for local stimulation of bone healing in both clinical application and research. STATEMENT OF SIGNIFICANCE: Our study provides evidence-based justification to promote the development and approval of more suitable and sophisticated delivery systems in bone healing research. Additionally, we stimulate researchers of the field to consider that the application of those scaffolds as a delivery system for new substances represents a delayed healing approach rather than a normal bone healing which could greatly impact the outcome of those studies and play a pivotal role in the translation to the clinics. Moreover, we provide impulses on underlying mechanism involving the roles of small-leucine rich proteoglycans (SLRP) for further detailed investigations.
尽管在过去几十年中已经开发出了几种用于骨再生的生物材料，但骨形态发生蛋白 2 的临床应用仅在应用于可吸收牛胶原蛋白 I 支架 (ACS)（Helistat；ACS-H）时才得到临床批准。在研究中，另一种 ACS，即 Lyostypt（ACS-L）经常作为骨相关研究中的支架使用。然而，直到今天，单独使用 ACS 对骨愈合的影响仍不清楚。出乎意料的是，与 ACS-L 相比，使用 ASC-H 进行的体外研究显示出对成骨分化的抑制作用和细胞活力的显著降低。在小鼠中，我们观察到在股骨切开术中在骨折间隙中应用 ACS-L 时，骨愈合明显延迟。我们的研究结果首次表明，两种 ACS-H 和 ACS-L 对骨形成都有负面影响，这表明在临床应用和研究中，需要更复杂的局部刺激骨愈合的输送系统。 意义声明：我们的研究为促进更合适和复杂的输送系统在骨愈合研究中的开发和批准提供了循证依据。此外，我们鼓励该领域的研究人员考虑将这些支架作为新物质的输送系统的应用代表了一种延迟愈合的方法，而不是正常的骨愈合，这可能会极大地影响这些研究的结果，并在向临床转化中发挥关键作用。此外，我们为进一步的详细研究提供了涉及小富含亮氨酸的蛋白聚糖 (SLRP) 作用的潜在机制的启示。
