Biomaterial scaffolds using traction-force-activated aptamers can repair damaged tissue by harvesting and releasing growth factors in response to cellular mechanical forces, according to reporting in Nature Materials.
Current clinical strategies rely on passive drug delivery or external triggers, which often require high doses of recombinant protein. The newly demonstrated traction-force-activated payloads, or TrAPs, attach inhibitory aptamers to biomaterial scaffolds. One end of the aptamer anchors to the scaffold, while the other connects to a cell-adhesive peptide handle such as RGD. When cells pull on the handle during adhesion and migration, the mechanical force unfolds the aptamer, releasing and activating the bound growth factor locally.
Tissue repair testing
In tests involving a six-millimeter femoral defect in rats, collagen sponges functionalized with vascular endothelial growth factor A TrAPs promoted significantly larger blood vessels after three weeks compared to control sponges and scrambled non-adhesive constructs. The system also demonstrated tissue repair modulation in mouse skin in vivo and human skin ex vivo.
The platform operates without requiring exogenous triggers, manufactured recombinant proteins, or cold-chain logistics. Empty TrAPs successfully harvested, concentrated, and redelivered multiple endogenous growth factors—including VEGF-A, hepatocyte growth factor, platelet-derived growth factor-BB, and fibroblast growth factor-2—from human primary cells and blood lysate at doses orders of magnitude lower than current clinical standards.
Unmodified oligonucleotide aptamers retained their binding functionality inside enzyme-rich wound environments. High-affinity binding held the growth factors in an inhibited state, preventing background signaling from passive diffusion even as the underlying carrier scaffold degraded.
