Intact and stable bone reconstruction is ideal for the treatment of periodontal bone destruction but remains challenging. In research, biomaterials are used to encapsulate stem cells or bioactive factors for periodontal bone regeneration, but, to the best of our knowledge, using a supramolecular hydrogel to encapsulate bioactive factors for their sustained release in bone defect areas to promote periodontal bone regeneration has not been reported. Herein, we used a well-studied hydrogelator, NapFFY, to coassemble with SDF-1 and BMP-2 to prepare a supramolecular hydrogel, SDF-1/BMP-2/NapFFY. In vitro and in vivo results indicated that these two bioactive factors were ideally, synchronously, and continuously released from the hydrogel to effectively promote the regeneration and reconstruction of periodontal bone tissues. Specifically, after the bone defect areas were treated with our SDF-1/BMP-2/NapFFY hydrogel for 8 weeks using maxillary critical-sized periodontal bone defect model rats, a superior bone regeneration rate of 56.7% bone volume fraction was achieved in these rats. We anticipate that our SDF-1/BMP-2/NapFFY hydrogel could replace bone transplantation in the clinic for the repair of periodontal bone defects and periodontally accelerated osteogenic orthodontics in the near future.

Magnetic resonance imaging (MRI) is advantageous in the diagnosis of deep internal cancers, but contrast agents (CAs) are always needed to improve MRI sensitivity. Gadolinium (Gd)-based agents are routinely used as T1-dominated CAs in clinic but using intracellularly formed Gd nanoparticles to enhance the T2-weighted MRI of tumor in vivo at high magnetic field has not been reported. Herein, we rationally designed a “smart” Gd-based probe Glu-Cys­(StBu)-Lys­(DOTA-Gd)-CBT (1), which was subjected to γ-glutamyltranspeptidase (GGT) cleavage and an intracellular CBT-Cys condensation reaction to form Gd nanoparticles (i.e., 1-NPs) to enhance the T2-weighted MR contrast of tumor in vivo at 9.4 T. Living cell experiments indicated that the 1-treated HeLa cells had an r2 value of 27.8 mM–1 s–1 and an r2/r1 ratio of 10.6. MR imaging of HeLa tumor-bearing mice indicated that the T2 MR contrast of the tumor enhanced 28.6% at 2.5 h post intravenous injection of 1. We anticipate that our probe 1 could be employed for T2-weighted MRI diagnosis of GGT-related cancers in the future when high magnetic field is available in clinic.

Chemiluminescence (CL) has a higher signal-to-noise ratio than fluorescence, but the use of CL to track an enzyme-instructed self-assembly (EISA) process has not been reported. In this work, by coincubation of the hydrogelator precursor Fmoc-Phe-Phe-Tyr(HPO)-OH (1P) and the CL agent AMPPD (2) with alkaline phosphatase (ALP), we employed CL to directly characterize and image the simultaneous EISA process of 1P. Hydrogelation processes of 1P with and without 2 and the CL properties of 2 with and without 1P under ALP catalysis were systematically studied. The results indicated that 2 is an ideal CL indicator for ALP-triggered hydrogelation of 1P. Using an IVIS optical imaging system, we obtained time-course CL images of 2 to track the simultaneous hydrogelation process of 1P in the same solution. We envision that our CL method could be employed to track more biological EISA events in the near future.

Alkaline phosphatase (ALP)-catalyzed hydrogelation has been extensively explored and found wide applications. Spectroscopic and electrochemical approaches are commonly employed for the detection of ALP activity. Herein, by rational design of a fluorescence probe Fmoc-K(FITC)FFYp (P1) (where FITC is fluorescein), we incorporated sol-gel transition with fluorescence "turn-off" and developed a new method for quantitative sensing ALP activity in vitro and in living cells. Under the catalysis of ALP, P1 was converted to hydrogelator Fmoc-K(FITC)FFY (1) which self-assembles into nanofibers to form Gel I. Accompanying this sol-gel transition, the fluorescence emission of P1 was turned off. Our assay was employed to detect ALP activity over the range of 0-2.8 U/mL with a limit of detection (LOD) of 0.06 U/mL. ALP-inhibitor-treated cell imaging indicated that P1 could be applied for sensing ALP activity in living cells. Our method provides a new option for real time and quantitative sensing ALP activity in vitro and even in living cells.