High-Axial-Aspect Tannic Acid Microparticles Facilitate Gelation and Injectability of Collagen-Based Hydrogels

Injectable collagen-based hydrogels offer great promise for tissue engineering and regeneration, but their use is limited by poor mechanical strength. Herein, we incorporate tannic acid (TA) to tailor the rheology of the corresponding hydrogels while simultaneously adding the therapeutic benefits inherent to this polyphenolic component. TA in the solution form and needle-shaped TA microparticles are combined with collagen and the respective systems studied for their time-dependent sol–gel transitions (from storage to body temperatures, 4–37 °C) as a function of TA concentration. Compared to systems incorporating TA microparticles, those with dissolved TA, applied at a similar concentration, generate a less significant enhancement of the elastic modulus. Premature gelation at a low temperature and associated colloidal arrest of the system are proposed as a main factor explaining this limited performance. A higher yield stress (elastic stress method) is determined for systems loaded with TA microparticles compared to the system with dissolved TA. These results are interpreted in terms of the underlying interactions of TA with collagen, as probed by spectroscopy and isothermal titration calorimetry. Importantly, hydrogels containing TA microparticles show high cell viability (human dermal fibroblasts) and comparative cellular activity relative to the collagen-only hydrogel. Overall, composite hydrogels incorporating TA microparticles demonstrate a new, simple, and better-performance alternative to cell culturing and difficult implantation scenarios.