What they built
Liu, Li, Yue, and colleagues at China Medical University in Shenyang, with collaborators at Sichuan University, report in Materials Today Bio (volume 39, article 103410, published online 2026-07-30, doi:10.1016/j.mtbio.2026.103410, open access) a single-stranded DNA aptamer they call Pt-1, evolved by Cell-SELEX against human dental pulp stem cells (hDPSCs). To reduce donor variation, the target cells were pooled from DPSCs isolated from 20 independent donors, extracted from premolars and third molars removed for orthodontic reasons. The 85-nucleotide library carried a 45-nucleotide randomized region. After 14 selection rounds, with a clear fluorescence shift by round 10 and a plateau at rounds 12 to 14, the group cloned and sequenced the enriched pool, picked eleven candidate aptamers (Pt-1 through Pt-11) from the dominant sequences, and found that Pt-1 bound DPSCs best, exceeding the established stem-cell aptamer Apt19S in flow-cytometric affinity assays. Binding kinetics gave a dissociation constant of 136 plus or minus 46 nM, and the aptamer showed no detectable degradation over 72 hours in culture medium or in human serum on urea-PAGE gels.
What Pt-1 marks
Specificity testing showed Pt-1 binding DPSCs but not HEK293 cells, and pretreatment with proteinase K or trypsin sharply cut binding, indicating a membrane protein target rather than a carbohydrate or lipid. The same probe recognized a broad set of mesenchymal stem cell lineages in flow cytometry: periodontal ligament stem cells, amniotic stem cells, adipose-derived stem cells, and bone marrow stem cells, all human. On sections of human dental pulp imaged with quantum-dot-conjugated Pt-1, labeled cells concentrated in the odontoblast layer and the perivascular niches of the root canal.
Sorting DPSCs by Pt-1 binding split the population into a Pt-1-high and a Pt-1-low subset. Both stayed positive for CD44 and CD146 and negative for CD34 and CD45, but they differed functionally: after 21 days of osteogenic induction the Pt-1-high cells formed markedly more Alizarin Red mineralized nodules, proliferated faster in CCK-8 assays, and expressed more RUNX2, DSPP, and DMP1 by qRT-PCR and western blotting.
To name the target, the group pulled down membrane proteins with aptamer-conjugated magnetic beads, saw a band near 20 kDa by silver-stained SDS-PAGE, and identified Caveolin-1 (Cav1) as the lead candidate by mass spectrometry. Blocking the Cav1 epitope with an antibody reduced Pt-1 binding, and raising or lowering Cav1 expression raised or lowered Pt-1 binding in step. The authors write the target as “Cav1-associated,” and their docking analysis of two hydrogen bonds plus salt bridges is computational support, not a resolved structure. Cav1’s reported role as a positive regulator of MSC proliferation and osteogenic differentiation through Wnt and TGF-beta signaling gives a plausible account of why the Pt-1-high subset behaves as the more potent one.
The hydrogel and the pulp experiment
The group conjugated amino-modified Pt-1 onto a chondroitin sulfate methacrylate (ChSMA) hydrogel through an AC-PEG-NHS linker; an XPS phosphorus 2p signal from the DNA backbone confirmed covalent incorporation, and the aptamer did not change pore architecture, swelling, compressive modulus, or cell viability. In Transwell assays the Pt-1 hydrogel drew significantly more DPSCs through the membrane than a hydrogel carrying Apt19S, the comparison the authors care about because Apt19S was selected against pluripotent cells, not mesenchymal ones.
The in vivo pulp test was an ectopic one. Standardized 6 mm human tooth roots were filled with bare, library-control, or Pt-1 hydrogel and implanted under the dorsal skin of four-week-old BALB/c nude mice. After four weeks, H&E staining of the root canals showed substantial infiltration of host MSC-like cells in the Pt-1-modified group. The abstract describes “rat models of dental pulp and femoral bone defects,” but the pulp model as written in the methods is this mouse ectopic root-fragment system, and the readout is cell infiltration into the canal space, not regenerated pulp tissue, new dentin, or an odontoblast layer.
Bone defect results
The same hydrogel was tested in an orthotopic rat femur defect (3 mm diameter, 2 mm depth in the lateral condyle), with blank, bare ChSMA, and Apt19S-hydrogel comparison groups, harvested at 3 and 6 weeks. Micro-CT morphometry at 3 weeks gave the Pt-1 group significantly higher bone volume fraction and trabecular number and lower trabecular spacing than all other groups, and at 6 weeks bone volume fraction and trabecular thickness remained significantly better than controls. H&E and Masson’s trichrome showed more mature, collagen-dense trabeculae in the Pt-1 group. Organ histology of heart, liver, spleen, lung, and kidney was unremarkable, liver, cardiac, and renal function panels stayed normal, and circulating IL-6 and TNF-alpha remained at low baseline levels.
Boundary and what it changes for the program
Everything in vivo is rodent, and the only orthotopic regeneration result is bone, not pulp. The pulp-side evidence stops at host cell recruitment into an empty human root canal sitting under mouse skin: no dentin bridge, no vascularized pulp-like tissue scoring, no functional readout. Group sizes are not stated in the text; only that data came from at least three independent experiments with P less than 0.05. The Cav1 identification, while supported by blocking and overexpression experiments, is hedged by the authors themselves as a “Cav1-associated” target.
For the pulp-dentin-repair program, the interesting move is the strategy, not the endpoint: recruit endogenous cells with a lineage-selected aptamer instead of transplanting expanded cells, which is the design behind the one controlled human result in this program (the Xuan et al. autologous DPSC trial, Science Translational Medicine 2018). A molecular handle that separates a high-potency DPSC subset and a hydrogel that holds that handle in a root canal is a step toward cell-free pulp repair, but on the current evidence it is a cell-recruitment tool demonstrated in ectopic implants, not a pulp regeneration result.
Provenance: grounded in the open-access full text of Liu X, Li X, Yue Y, Zheng Y, Huang W, Niu J, Sun H, Xue M, Ao Q, Xu Y, Yu Y, Zhou Q, Yu T. Selection of a novel MSC-targeted aptamer Pt-1 and its functionalized hydrogel for tissue regeneration. Materials Today Bio. 2026;39:103410. doi:10.1016/j.mtbio.2026.103410, retrieved as PMC13382431 and read in full. Method and sourcing standard at /method/.