关键词: Bone tissue engineering Exosome Freeze-drying PAA Tricalcium phosphate nanoparticles

来  源:   DOI:10.34172/bi.2022.24142   PDF(Pubmed)

Abstract:

UNASSIGNED: This study focused on preparing a multiscale three-dimensional (3D) scaffold using tricalcium phosphate nanoparticles (triCaPNPs) in a substrate of poly(acrylic acid) (PAA) polymer for controlled release of exosomes in bone tissue engineering.
UNASSIGNED: A scaffold was fabricated with a material mixture containing acrylic acid (AA) monomer, N,N\'-methylenebisacrylamide (MBAA), ammonium persulfate (APS), sodium bicarbonate (SBC), and triCaPNPs called composite scaffold (PAA/triCaPNPs) via cross-linking and freeze-drying methods. The synthesis process was easy and without complex multi-steps. Through mimicking the hybrid (organic-inorganic) structure of the bone matrix, we here chose triCaPNPs for incorporation into the PAA polymer. After assessing the physicochemical properties of the scaffold, the interaction of the scaffold with human umbilical cord mesenchymal stem cells (UC-MSCs) such as attachment, proliferation, and differentiation to osteoblast cells was evaluated. In addition, we used DiI-labeled exosomes to verify the exosome entrapment and release from the scaffold.
UNASSIGNED: The polymerization reaction of 3D scaffold was successful. Based on results of physicochemical properties, the presence of nanoparticles in the composite scaffold enhanced the mechanical stiffness, boosted the porosity with a larger pore size range, and offered better hydrophilicity, all of which would contribute to greater cell penetration, proliferation, and then better bone differentiation. In addition, our results indicated that our scaffold could take up and release exosomes, where the exosomes released from it could significantly enhance the osteogenic commitment of UC-MSCs.
UNASSIGNED: The current research is the first study fabricating a multiscale scaffold using triCaPNPs in the substrate of PPA polymer using a cross-linker and freeze-drying process. This scaffold could mimic the nanoscale structure and chemical combination of native bone minerals. In addition, our results suggest that the PAA/triCaPNPs scaffold could be beneficial to achieve controlled exosome release for exosome-based therapy in bone tissue engineering.
摘要:

这项研究的重点是在聚(丙烯酸)(PAA)聚合物的基底中使用磷酸三钙纳米颗粒(triCaPNPs)制备多尺度三维(3D)支架,用于骨组织工程中外泌体的控释。
用含有丙烯酸(AA)单体的材料混合物制造支架,N,N'-亚甲基双丙烯酰胺(MBAA),过硫酸铵(APS),碳酸氢钠(SBC),和triCaPNP通过交联和冷冻干燥方法称为复合支架(PAA/triCaPNP)。该合成方法简单且没有复杂的多步骤。通过模拟骨基质的混合(有机-无机)结构,我们在这里选择triCaPNP用于掺入PAA聚合物。在评估支架的物理化学性质后,支架与人脐带间充质干细胞(UC-MSCs)的相互作用,扩散,并评估向成骨细胞的分化。此外,我们使用DiI标记的外泌体来验证外泌体的截留和从支架中的释放。
3D支架的聚合反应是成功的。根据物理化学性质的结果,复合支架中纳米颗粒的存在增强了机械刚度,通过更大的孔径范围提高了孔隙率,并提供更好的亲水性,所有这些都将有助于更大的细胞渗透,扩散,然后更好的骨分化。此外,我们的结果表明,我们的支架可以吸收和释放外泌体,其中从其释放的外泌体可以显着增强UC-MSCs的成骨承诺。
当前的研究是第一个使用交联剂和冷冻干燥工艺在PPA聚合物的底物中使用triCaPNP制造多尺度支架的研究。该支架可以模拟天然骨矿物质的纳米级结构和化学组合。此外,我们的结果表明,PAA/triCaPNPs支架可能有利于实现外泌体的受控释放,用于骨组织工程中基于外泌体的治疗。
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