Osteoblastic Cell Sheet Engineering Using P(VCL-HEMA)-Based Thermosensitive Hydrogels Doped with pVCL@Icariin Nanoparticles Obtained with Supercritical CO₂-SAS

Abstract

New clinical strategies for treating severe bone and cartilage injuries are required, especially for use in combination with implant procedures. For this purpose, p(VCL-co-HEMA) thermosensitive hydrogels have been activated with icariin-loaded nanoparticles to be used as bone-cell-harvesting platforms. Supercritical CO2-SAS technology has been applied to encapsulate icariin, a small molecule that is involved in osteoblastic differentiation. Thus, physical-chemical analysis, including swelling and transmittance, showed the impact of HEMA groups in hydrogel composition. Moreover, icariin (ICA) release from p(VCL-co-HEMA) platforms, including pVCL@ICA nanoparticles, has been studied to evaluate their efficacy in relevant conditions. Finally, the thermosensitive hydrogels’ cell compatibility, transplant efficiency, and bone differentiation capacity were tested. This study identifies the optimal formulations for icariin-activated hydrogels for both control and HEMA formulations. Using this technique, osteoblastic sheets that were rich in collagen type I were successfully transplanted and recultivated, maintaining an optimal extracellular matrix (ECM) composition. These findings suggest a new cell-sheet-based therapy for bone regeneration purposes using customized and NP-activated pVCL-based cell platforms.

Keywords

• thermosensitive hydrogel
• cell sheet engineering
• bone differentiation
• icariin
• supercritical CO₂ technology
• drug delivery