Aptamer-Based Polyvalent Ligands for Regulated Cell Attachment on the Hydrogel Surface

Natural biomolecules are often used to functionalize materials to achieve desired cell-material interactions. However, their applications can be limited owing to denaturation during the material functionalization process. Therefore, efforts have been made to develop synthetic ligands with polyvalence as alternatives to natural affinity biomolecules for the synthesis of functional materials and the control of cell-material interactions. This work was aimed at investigating the capability of a hydrogel functionalized with a novel polyvalent aptamer in inducing cell attachment in dynamic flow and releasing the attached cells in physiological conditions through a hybridization reaction. The results show that the polyvalent aptamer could induce cell attachment on the hydrogel in dynamic flow. Moreover, cell attachment on the hydrogel surface was significantly influenced by the value of shear stress. The cell density on the hydrogel was increased from 40 cells/mm² to nearly 700 cells/mm² when the shear stress was decreased from 0.05 to 0.005 Pa. After the attachment onto the hydrogel surface, approximately 95% of the cells could be triggered to detach within 20 min by using an oligonucleotide complementary sequence that displaced polyvalent aptamer strands from the hydrogel surface. While it was found that the cell activity was reduced, the live/dead staining results show that ≥98% of the detached cells were viable. Therefore, this work has suggested that the polyvalent aptamer is a promising synthetic ligand for the functionalization of materials for regulated cell attachment

Chimeric Aptamer–Gelatin Hydrogels as an Extracellular Matrix Mimic for Loading Cells and Growth Factors

It is important to synthesize materials to recapitulate critical functions of biological systems for a variety of applications such as tissue engineering and regenerative medicine. The purpose of this study was to synthesize a chimeric hydrogel as a promising extracellular matrix (ECM) mimic using gelatin, a nucleic acid aptamer, and polyethylene glycol. This hydrogel had a macroporous structure that was highly permeable for fast molecular transport. Despite its high permeability, it could strongly sequester and sustainably release growth factors with high bioactivity. Notably, growth factors retained in the hydrogel could maintain ∼50% bioactivity during a 14-day release test. It also provided cells with effective binding sites, which led to high efficiency of cell loading into the macroporous hydrogel matrix. When cells and growth factors were coloaded into the chimeric hydrogel, living cells could still be observed by day 14 in a static serum-reduced culture condition. Thus, this chimeric aptamer–gelatin hydrogel constitutes a promising biomolecular ECM mimic for loading cells and growth factors

Aptamer-Functionalized Hydrogel for Self-Programmed Protein Release via Sequential Photoreaction and Hybridization

A dynamic hydrogel that sequentially responds to two independent but interrelated physical and biomolecular signals was reported in this work. Once hit by an external light signal, an immobilized internal molecular signal is activated and freed via photoreaction; and subsequently the freed molecular signal works as a self-programming factor of the hydrogel to induce the dissociation of a biomolecular complex to release protein via a hybridization reaction. Notably, pulsatile external light input can be converted to periodical protein output from the hydrogel to regulate cell migration. Thus, this hydrogel holds potential as a self-programming platform for biological and biomedical applications such as controlled release of bioactive substances