Björkenheim R, Jämsen E, Eriksson E, Uppstu P, Aalto-Setälä L, Hupa L, Eklund K K, Ainola M, Lindfors N C, Pajarinen J
Department of Musculoskeletal and Plastic Surgery, University of Helsinki, Helsinki University Hospital, Topeliuksenkatu 5B, 3rd floor, 00260 Helsinki, Finland.
Eur Cell Mater. 2021 Jan 3;41:15-30. doi: 10.22203/eCM.v041a02.
Bioactive glasses (BAG) are used as bone-graft substitutes in orthopaedic surgery. A specific BAG scaffold was developed by sintering BAG-S53P4 granules. It is hypothesised that this scaffold can be used as a bone substitute to fill bone defects and induce a bioactive membrane (IM) around the defect site. Beyond providing the scaffold increased mechanical strength, that the initial inflammatory reaction and subsequent IM formation can be enhanced by coating the scaffolds with poly(DL-lactide-co-glycolide) (PLGA) is also hypothesised. To study the immunomodulatory effects, BAG-S53P4 (± PLGA) scaffolds were placed on monolayers of primary human macrophage cultures and the production of various pro- and anti-inflammatory cytokines was assessed using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and ELISA. To study the osteogenic effects, BAG-S53P4 (± PLGA) scaffolds were cultured with rabbit mesenchymal stem cells and osteogenic differentiation was evaluated by RT-qPCR and matrix mineralisation assays. The scaffold ion release was quantified and the BAG surface reactivity visualised. Furthermore, the pH of culture media was measured. BAG-S53P4 scaffolds had both anti-inflammatory and osteogenic properties that were likely attributable to alkalinisation of the media and ion release from the scaffold. pH change, ion release, and immunomodulatory properties of the scaffold could be modulated by the PLGA coating. Contrary to the hypothesis, the coating functioned by attenuating the BAG surface reactions and subsequent anti-inflammatory properties, rather than inducing an elevated inflammatory response compared to BAG-S53P4 alone. These results further validated the use of BAG-S53P4 (± PLGA) scaffolds as bone substitutes and indicate that scaffold properties can be tailored to a specific clinical need.
生物活性玻璃（BAG）在骨科手术中用作骨移植替代物。通过烧结BAG-S53P4颗粒开发了一种特定的BAG支架。据推测，这种支架可用作骨替代物来填充骨缺损并在缺损部位诱导形成生物活性膜（IM）。除了为支架提供更高的机械强度外，还推测通过用聚（DL-丙交酯-共-乙交酯）（PLGA）涂覆支架可以增强初始炎症反应和随后的IM形成。为了研究免疫调节作用，将BAG-S53P4（±PLGA）支架放置在原代人巨噬细胞培养物的单层上，并使用逆转录定量聚合酶链反应（RT-qPCR）和酶联免疫吸附测定（ELISA）评估各种促炎和抗炎细胞因子的产生。为了研究成骨作用，将BAG-S53P4（±PLGA）支架与兔间充质干细胞一起培养，并通过RT-qPCR和基质矿化测定评估成骨分化。对支架离子释放进行定量，并观察BAG表面反应性。此外，测量了培养基的pH值。BAG-S53P4支架具有抗炎和成骨特性，这可能归因于培养基的碱化和支架的离子释放。支架的pH变化、离子释放和免疫调节特性可通过PLGA涂层进行调节。与假设相反，该涂层通过减弱BAG表面反应和随后的抗炎特性起作用，而不是与单独的BAG-S53P4相比诱导更高的炎症反应。这些结果进一步验证了BAG-S53P4（±PLGA）支架作为骨替代物的用途，并表明可以根据特定的临床需求调整支架特性。
