Department of Chemistry "Giacomo Ciamician" and INSTM UdR of Bologna, University of Bologna, Via Selmi, 2, 40126 Bologna, Italy.
Interdepartmental Center for Industrial Research on Advanced Applications in Mechanical Engineering and Materials Technology, CIRI-MAM, University of Bologna, Viale Risorgimento, 2, 40136 Bologna, Italy.
Biomacromolecules. 2023 Mar 13;24(3):1366-1376. doi: 10.1021/acs.biomac.2c01383. Epub 2023 Feb 7.
The possibility of incorporating HS slow-release donors inside biomimetic scaffolds can pave the way to new approaches in the field of tissue regeneration and anti-inflammatory treatment. In the present work, GYY4137, an easy-to-handle commercially available Lawesson's reagent derivative, has been successfully incorporated inside biomimetic silk fibroin-based electrospun scaffolds. Due to the instability of GYY4137 in the solvent needed to prepare silk fibroin solutions (formic acid), the electrospinning of the donor together with the silk fibroin turned out to be impossible. Therefore, a multilayer structure was realized, consisting of a PLGA mat containing GYY4137 sandwiched between two silk fibroin nanofibrous layers. Before their use in the multilayer scaffold, the silk fibroin mats were treated in ethanol to induce crystalline phase formation, which conferred water-resistance and biomimetic properties. The morphological, thermal, and chemical properties of the obtained scaffolds were thoroughly characterized by SEM, TGA, DSC, FTIR, and WAXD. Multilayer devices showing two different concentrations of the HS donor, i.e., 2 and 5% w/w with respect to the weight of PLGA, were analyzed to study their HS release and biological properties, and the results were compared with those of the sample not containing GYY4137. The HS release analysis was carried out according to an "ad-hoc" designed procedure based on a validated high-performance liquid chromatography method. The proposed analytical approach demonstrated the slow-release kinetics of HS from the multilayer scaffolds and its tunability by acting on the donor's concentration inside the PLGA nanofibers. Finally, the devices were tested in biological assays using bone marrow-derived mesenchymal stromal cells showing the capacity to support cell spreading throughout the scaffold and prevent cytotoxicity effects in serum starvation conditions. The resulting devices can be exploited for applications in the tissue engineering field since they combine the advantages of controlled HS release kinetics and the biomimetic properties of silk fibroin nanofibers.
将 HS 缓控释供体纳入仿生支架的可能性为组织再生和抗炎治疗领域开辟了新的途径。在本工作中，GYY4137（一种易于处理的市售 Lawesson 试剂衍生物）已成功地纳入仿生丝素基静电纺丝支架中。由于 GYY4137 在制备丝素溶液（甲酸）所需的溶剂中不稳定，因此供体与丝素共纺是不可能的。因此，实现了一种多层结构，由含有 GYY4137 的 PLGA 垫夹在两层丝素纳米纤维层之间组成。在将丝素垫用于多层支架之前，先用乙醇处理以诱导结晶相形成，从而赋予其耐水性和仿生特性。通过 SEM、TGA、DSC、FTIR 和 WAXD 对获得的支架的形态、热和化学性质进行了彻底表征。分析了具有两种不同 HS 供体浓度（即相对于 PLGA 重量为 2%和 5%w/w）的多层装置，以研究其 HS 释放和生物学性质，并将结果与不含 GYY4137 的样品进行比较。HS 释放分析根据基于验证的高效液相色谱法设计的“专用”程序进行。所提出的分析方法证明了 HS 从多层支架中的缓慢释放动力学及其通过作用于 PLGA 纳米纤维内供体浓度的可调性。最后，使用骨髓间充质基质细胞在生物测定中测试了这些装置，结果表明它们能够支持细胞在支架中扩展，并防止在血清饥饿条件下的细胞毒性作用。所得装置可用于组织工程领域，因为它们结合了 HS 释放动力学的可控性和丝素纳米纤维的仿生特性。
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