Technische Universität Braunschweig, Institut für Pharmazeutische Technologie und Biopharmazie, Mendelssohnstraβe 1, 38106 Braunschweig, Germany.
Technische Universität Braunschweig, Institut für Technische Chemie, Hagenring 30, 38106 Braunschweig, Germany.
ACS Biomater Sci Eng. 2024 Jan 8;10(1):89-98. doi: 10.1021/acsbiomaterials.1c01585. Epub 2022 May 27.
Temporally and spatially controlled growth factor release from a polycaprolactone fiber mat, which also provides a matrix for directional cell colonization and infiltration, could be a promising regenerative approach for degenerated tendon-bone junctions. For this purpose, polycaprolactone fiber mats were coated with tailored chitosan-based nanogels to bind and release the growth factors bone morphogenetic protein 2 (BMP-2) and transforming growth factor-β (TGF-β), respectively. In this work we provide meaningful data for the understanding of the drug delivery performance and sterilizability of novel implant prototypes in order to lay the foundation for testing. ELISA-based release studies were used to investigate the spatial and temporal control of release, as well as the influence of radiation sterilization on protein activity and release behavior. Layer-by-layer coatings based on BMP-2-containing chitosan tripolyphosphate nanogel particles and negatively charged alginate showed a good sustainment of BMP-2 release from chemically modified polycaprolactone fiber mats. Release control improved with increasing layer numbers. The approach of controlling the release via a barrier of cross-linked chitosan azide proved less promising. By using a simple, partial immersion-based dip-coating process, it was possible to apply opposing gradients of the growth factors BMP-2 and TGF-β. Final radiation sterilization of the growth factor-loaded implant prototypes resulted in a radiation dose-correlated degradation of the growth factors, which could be prevented by lyophilization into protective matrices. For the manufacture of sterile implants, the growth factor loading step must probably be carried out under aseptic conditions. The layer-by-layer coated implant prototypes provided sustained release from opposing gradients of the growth factors BMP-2 and TGF-β and thus represent a promising approach for the restoration of tendon-bone defects.
从聚己内酯纤维垫中时空控制生长因子的释放，这也为定向细胞定植和渗透提供了基质，可能是一种有前途的退行性肌腱-骨结合处的再生方法。为此，用定制的壳聚糖纳米凝胶对聚己内酯纤维垫进行了涂层，以分别结合和释放生长因子骨形态发生蛋白 2（BMP-2）和转化生长因子-β（TGF-β）。在这项工作中，我们提供了有意义的数据，用于了解新型植入物原型的药物输送性能和可灭菌性，以便为测试奠定基础。基于 ELISA 的释放研究用于研究释放的时空控制，以及辐射灭菌对蛋白质活性和释放行为的影响。基于含有 BMP-2 的壳聚糖三聚磷酸钠纳米凝胶颗粒和带负电荷的海藻酸钠的层层涂层显示出对化学修饰的聚己内酯纤维垫中 BMP-2 释放的良好维持作用。随着层数量的增加，释放控制得到改善。通过交联壳聚糖叠氮化物的屏障控制释放的方法证明效果较差。通过使用简单的、基于部分浸入的浸涂工艺，可以施加生长因子 BMP-2 和 TGF-β 的相反梯度。最终对负载生长因子的植入物原型进行辐射灭菌会导致生长因子发生与辐射剂量相关的降解，通过冻干到保护性基质中可以防止这种降解。为了制造无菌植入物，生长因子加载步骤可能必须在无菌条件下进行。层状涂层的植入物原型提供了相反梯度的生长因子 BMP-2 和 TGF-β 的持续释放，因此代表了恢复肌腱-骨缺陷的有前途的方法。
