Force-responsive biomaterials drive tissue repair by harnessing endogenous growth factors

Materials enabling cell-responsive delivery of endogenous biologics, such as growth factors, have the potential to modulate wound repair cost-effectively and safely. Unlike passive drug delivery strategies that require supraphysiological doses of recombinant protein or stimuli-responsive systems that rely on external triggers, we demonstrate a strategy that harnesses cellular traction forces as an intrinsic delivery trigger. Traction force-Activated Payloads (TrAPs) are bioinspired aptamer constructs attached to biomaterial scaffolds that selectively harvest, concentrate, and reactivate multiple endogenous growth factors from cells, injury sites, and blood lysate in vivo (rat femur, mouse skin) and ex vivo (human skin), at doses orders of magnitude lower than current clinical standards. Unmodified oligonucleotide aptamers retain functionality in enzyme-rich wound environments, substantially expanding the translational potential of nucleic acid-based therapeutics. The ability to harvest and redeliver endogenous growth factors without exogenous triggers, recombinant proteins, or cold-chain logistics via mechanoresponsive biomaterials opens possibilities for accessible, cost-effective combinatorial biologic therapies.