Composite hydrogels with controlled degradation in 3D printed scaffolds for programmed cell delivery.

Controlled cell delivery has shown some promising outcomes compared with traditional cell delivery approaches over the past decades, and strategies focused on optimization or engineering of controlled cell delivery have been intensively studied. In this report, we demonstrate the fabrication of a 3D printed hydrogel scaffold infused with degradable PEGPLA/NB composite hydrogel core for controlled cell delivery with improved cell viability and facile tunability. The 3D printed poly(ethylene glycol) diacrylate (PEGDA) scaffold with specifically designed architectures can provide mechanical support while allowing bidirectional diffusion of small molecules, thus permitting structural integrity and long-term cell viability. Poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA), which is highly susceptible to hydrolysis, however, the acrylation reactions it utilizes for chain growth have been reported as toxic to cells. Poly(ethylene glycol) norbornene (PEGNB), validated for its excellent cytocompatibility, was therefore mixed and infused together with PLA-PEG-PLA into the printed PEGDA scaffold. Cells encapsulated microfluidically into PEGNB microspheres and then polymerized within PEGPLA/NB composite hydrogel maintained excellent viability over a week. Controlled cell release was achieved via the manipulation of PEGPLA/NB composition. By increasing PEGNB proportion in the core, cell release was significantly slowed, while increasing PLA-PEGPLA proportion eventually resulted in very robust cell release within a short time frame. Functionality of released cells was validated by their cell viability and proliferation potential. In summary, we have shown this droplet-microencapsulation technique coupled with composite degradable hydrogel and 3D printing could offer an alternative route for controlled cell delivery. INDEX TERMS.