Complex Tissue Regeneration (CTR), MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands.
Aachen-Maastricht Institute for Biobased Materials (AMIBM), Maastricht University, Geleen, The Netherlands.
Tissue Eng Part C Methods. 2022 Jul;28(7):335-350. doi: 10.1089/ten.TEC.2022.0041.
Synthetic thermoplastic polymers are a widespread choice as material candidates for scaffolds for tissue engineering (TE), thanks to their ease of processing and tunable properties with respect to biological polymers. These features made them largely employed in melt-extrusion-based additive manufacturing, with particular application in hard-TE. In this field, high molecular weight () polymers ensuring entanglement network strength are often favorable candidates as scaffold materials because of their enhanced mechanical properties compared with lower grades. However, this is accompanied by high viscosities once processed in molten conditions, which requires driving forces not always accessible technically or compatible with often chemically nonstabilized biomedical grades. When possible, this is circumvented by increasing the operating temperature, which often results in polymer chain scission and consequent degradation of properties. In addition, synthetic polymers are mostly considered bioinert compared with biological materials, and additional processing steps are often required to make them favorable for tissue regeneration. In this study, we report the plasticization of a common thermoplastic polymer with cholecalciferol, the metabolically inactive form of vitamin D3 (VD3). Plasticization of the polymer allowed us to reduce its melt viscosity, and therefore the energy requirements (mechanical [torque] and heat [temperature]) for extrusion, limiting ultimately polymer degradation. In addition, we evaluated the effect of cholecalciferol, which is more easily available than its active counterpart, on the osteogenic differentiation of human mesenchymal stromal cells (hMSCs). Results indicated that cholecalciferol supported osteogenic differentiation more than the osteogenic culture medium, suggesting that hMSCs possess the enzymatic toolbox for VD3 metabolism. Impact statement Limitations in mechanical and biological performances of scaffolds manufactured through melt deposition may result from material thermal degradation during processing and inherent bioinertness of synthetic polymers. Current approaches involve the incorporation of chemical additives to reduce the extent of thermal degradation, which are often nonbiocompatible or may lead to uncontrolled modifications to the polymer structure. Lack of polymer bioactivity is tackled by postfunctionalization methods that often involve extra processes extending scaffold production time. Therefore, new methods to improve scaffolds performances should consider preserving the integrity of the molecular structure and improving biological responsiveness of the material while keeping the process as straightforward as possible.
合成热塑性聚合物由于其易于加工和可针对生物聚合物调整的特性，是组织工程（TE）支架的广泛选择材料。这些特点使它们在基于熔融挤出的增材制造中得到了大量应用，特别是在硬组织工程中。在这个领域中，具有高分子量（）的聚合物由于其与较低等级相比具有增强的机械性能，通常是支架材料的首选。然而，这伴随着在熔融状态下加工时的高粘度，这需要技术上不一定可行或与经常化学不稳定的生物医学等级不兼容的驱动力。在可能的情况下，通过提高操作温度来避免这种情况，这通常会导致聚合物链的断裂和随后的性能降解。此外，与生物材料相比，合成聚合物通常被认为是生物惰性的，并且通常需要额外的处理步骤才能使其有利于组织再生。在这项研究中，我们报告了胆钙化醇（维生素 D3 的无代谢活性形式）对一种常见热塑性聚合物的增塑作用。聚合物的增塑作用使我们能够降低其熔体粘度，从而降低挤出所需的能量（机械[扭矩]和热[温度]），最终限制聚合物降解。此外，我们评估了胆钙化醇（比其活性对应物更容易获得）对人间充质基质细胞（hMSC）成骨分化的影响。结果表明，胆钙化醇比成骨培养基更支持成骨分化，这表明 hMSC 具有维生素 D3 代谢的酶工具箱。影响说明 通过熔融沉积制造的支架在机械和生物学性能方面存在限制，这可能是由于加工过程中的材料热降解和合成聚合物的固有生物惰性所致。目前的方法涉及添加化学添加剂来减少热降解的程度，但这些添加剂往往不具有生物相容性，或者可能导致聚合物结构的不可控修饰。聚合物缺乏生物活性是通过后功能化方法来解决的，这些方法通常涉及额外的过程，延长了支架生产时间。因此，提高支架性能的新方法应考虑在保持分子结构完整性的同时，提高材料的生物学响应性，同时使该过程尽可能简单。
