Faculty of Science and Technology, Technical Medical Centre, Department of Developmental BioEngineering, University of Twente, Drienerlolaan 5, 7522 NB, Enschede, The Netherlands.
Nat Commun. 2019 Sep 25;10(1):4347. doi: 10.1038/s41467-019-12390-4.
Spatiotemporal control over engineered tissues is highly desirable for various biomedical applications as it emulates the dynamic behavior of natural tissues. Current spatiotemporal biomaterial functionalization approaches are based on cytotoxic, technically challenging, or non-scalable chemistries, which has hampered their widespread usage. Here we report a strategy to spatiotemporally functionalize (bio)materials based on competitive supramolecular complexation of avidin and biotin analogs. Specifically, an injectable hydrogel is orthogonally post-functionalized with desthiobiotinylated moieties using multivalent neutravidin. In situ exchange of desthiobiotin by biotin enables spatiotemporal material functionalization as demonstrated by the formation of long-range, conformal, and contra-directional biochemical gradients within complex-shaped 3D hydrogels. Temporal control over engineered tissue biochemistry is further demonstrated by timed presentation and sequestration of growth factors using desthiobiotinylated antibodies. The method's universality is confirmed by modifying hydrogels with biotinylated fluorophores, peptides, nanoparticles, enzymes, and antibodies. Overall, this work provides a facile, cytocompatible, and universal strategy to spatiotemporally functionalize materials.
时空控制工程组织对于各种生物医学应用是非常理想的，因为它模拟了天然组织的动态行为。目前的时空生物材料功能化方法基于细胞毒性、技术挑战性或不可扩展的化学，这阻碍了它们的广泛应用。在这里，我们报告了一种基于亲和素和生物素类似物的竞争性超分子络合来时空功能化（生物）材料的策略。具体来说，使用多价中性亲和素对可注射水凝胶进行正交后修饰，带有去硫生物素化部分。去硫生物素通过生物素的原位交换可以实现时空材料功能化，这可以通过在复杂形状的 3D 水凝胶内形成长程、共形和反方向的生化梯度来证明。通过使用去硫生物素化抗体来定时呈现和隔离生长因子，进一步实现了对工程组织生物化学的时间控制。该方法的通用性通过用生物素化荧光团、肽、纳米粒子、酶和抗体修饰水凝胶得到了证实。总的来说，这项工作提供了一种简便、细胞相容和通用的时空功能化材料的策略。
