National Interuniversity Consortium of Material Science and Technology, Florence, Italy; BIOtech Research Center and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Department of Industrial Engineering, University of Trento, Trento, Italy.
BIOtech Research Center and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Department of Industrial Engineering, University of Trento, Trento, Italy.
Biomater Adv. 2024 Jul;161:213887. doi: 10.1016/j.bioadv.2024.213887. Epub 2024 May 6.
Critical size bone defects cannot heal without aid and current clinical approaches exhibit some limitations, underling the need for novel solutions. Silk fibroin, derived from silkworms, is widely utilized in tissue engineering and regenerative medicine due to its remarkable properties, making it a promising candidate for bone tissue regeneration in vitro and in vivo. However, the clinical translation of silk-based materials requires refinements in 3D architecture, stability, and biomechanical properties. In earlier research, improved mechanical resistance and stability of chemically crosslinked methacrylate silk fibroin (Sil-Ma) sponges over physically crosslinked counterparts were highlighted. Furthermore, the influence of photo-initiator and surfactant concentrations on silk properties was investigated. However, the characterization of sponges with Sil-Ma solution concentrations above 10 % (w/V) was hindered by production optimization challenges, with only cell viability assessed. This study focuses on the evaluation of methacrylate sponges' suitability as temporal bone tissue regeneration scaffolds. Sil-Ma sponge fabrication at a fixed concentration of 20 % (w/V) was optimized and the impact of photo-initiator (LAP) concentrations and surfactant (Tween 80) presence/absence was studied. Their effects on pore formation, silk secondary structure, mechanical properties, and osteogenic differentiation of hBM-MSCs were investigated. We demonstrated that, by tuning silk sponges' composition, the optimal combination boosted osteogenic gene expression, offering a strategy to tailor biomechanical properties for effective bone regeneration. Utilizing Design of Experiment (DoE), correlations between sponge composition, porosity, and mechanical properties are established, guiding tailored material outcomes. Additionally, correlation matrices elucidate the microstructure's influence on gene expressions, providing insights for personalized approaches in bone tissue regeneration.
临界尺寸骨缺损在没有辅助的情况下无法愈合，而当前的临床方法存在一些局限性，因此需要新的解决方案。丝素蛋白来源于家蚕，由于其优异的性能，广泛应用于组织工程和再生医学领域，是一种很有前途的体外和体内骨组织再生候选材料。然而，丝基材料的临床转化需要改进其 3D 结构、稳定性和生物力学性能。在早期的研究中，强调了化学交联甲基丙烯酰丝素（Sil-Ma）海绵在机械强度和稳定性方面优于物理交联的对应物。此外，还研究了光引发剂和表面活性剂浓度对丝素性能的影响。然而，由于生产优化方面的挑战，Sil-Ma 溶液浓度高于 10%（w/V）的海绵的特性难以进行表征，仅评估了细胞活力。本研究聚焦于评估甲基丙烯酰基海绵作为临时性骨组织再生支架的适用性。优化了固定浓度为 20%（w/V）的 Sil-Ma 海绵的制备，并研究了光引发剂（LAP）浓度和表面活性剂（Tween 80）存在/不存在对其的影响。研究了它们对孔形成、丝素二级结构、力学性能和 hBM-MSCs 成骨分化的影响。我们证明，通过调整丝素海绵的组成，可以优化最佳组合，从而增强成骨基因表达，为有效骨再生提供了一种定制生物力学性能的策略。利用实验设计（DoE），建立了海绵组成、孔隙率和力学性能之间的相关性，指导定制材料的结果。此外，相关矩阵阐明了微结构对基因表达的影响，为骨组织再生的个性化方法提供了见解。
