Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 763 Heguang Road, Changchun 130021, P.R. China.
Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P.R. China.
Nano Lett. 2022 May 25;22(10):3904-3913. doi: 10.1021/acs.nanolett.2c00057. Epub 2022 May 6.
Physiological microenvironment engineering has shown great promise in combating a variety of diseases. Herein, we present the rational design of reinforced and injectable blood-derived protein hydrogels (PDA@SiO-PRF) composed of platelet-rich fibrin (PRF), polydopamine (PDA), and SiO nanofibers that can act as dual-level regulators to engineer the microenvironment for personalized bone regeneration with high efficacy. From the biophysical level, PDA@SiO-PRF with high stiffness can withstand the external loading and maintaining the space for bone regeneration in bone defects. Particularly, the reinforced structure of PDA@SiO-PRF provides bone extracellular matrix (ECM)-like functions to stimulate osteoblast differentiation via Yes-associated protein (YAP) signaling pathway. From the biochemical level, the PDA component in PDA@SiO-PRF hinders the fast degradation of PRF to release autologous growth factors in a sustained manner, providing sustained osteogenesis capacity. Overall, the present study offers a dual-level strategy for personalized bone regeneration by engineering the biophysiochemical microenvironment to realize enhanced osteogenesis efficacy.
生理微环境工程在治疗多种疾病方面显示出巨大的潜力。在此，我们提出了一种合理设计的增强型和可注射的血液来源的蛋白质水凝胶（PDA@SiO-PRF），由富含血小板的纤维蛋白（PRF）、聚多巴胺（PDA）和 SiO 纳米纤维组成，可作为双水平调节剂，用于高效地个性化骨再生的微环境工程。从生物物理水平来看，具有高刚性的 PDA@SiO-PRF 可以承受外部负载并维持骨缺损中骨再生的空间。特别是，PDA@SiO-PRF 的增强结构提供了类似于骨细胞外基质（ECM）的功能，通过 Yes 相关蛋白（YAP）信号通路刺激成骨细胞分化。从生化水平来看，PDA@SiO-PRF 中的 PDA 成分阻碍了 PRF 的快速降解，以持续的方式释放自体生长因子，提供持续的成骨能力。总的来说，本研究通过工程生物物理化学微环境提供了一种个性化骨再生的双水平策略，以实现增强的成骨效果。
