Engineering a mechanically tunable DNA-Collagen hydrogel system

Session Takeaways:
This research represents a novel biomaterial exploration of Nucleic Acid- Collagen Complexes, aiming to harness the inherent properties of DNA to tune bulk hydrogel characteristics such as gelation kinetics and mechanical strength. By leveraging the unique union of engineered DNA aptamers and collagen, we provide a platform with wide-ranging applicability, paving the way for improved therapeutic outcomes and biomimetic extracellular matrices. In the long term, our aim is to create a material system that can be customized and utilized by biomedical researchers to investigate various cell processes relevant to human health

Introduction:
Nucleic-acid collagen complexes (NACCs) are being examined as a promising hydrogel biomaterial with potential applications in tissue engineering, drug delivery, and wound healing. The rapid self-assembly after mixing short, single-stranded DNA and type 1 collagen has been shown to form nanoparticles, microfibers and hydrogels without the need for external stimuli or complex chemistries. NACCs are poised to be an advancement over current hydrogel technologies in terms of biomimicry, bioactivity, simplicity, biocompatibility and tunability. This is particularly true when considering the use of DNA aptamers within the complex to provide the hydrogel system with targeted bioactivity. For example, NACCs fabricated with a DNA aptamer targeting VEGFR2 signaling show enhanced angiogenic response from endothelial cells. Additionally, the inclusion of mineralization solutions allows for control over the mineralization process, opening up possibilities for bone tissue engineering.

Methods:
In this study, we explore the tunability of gels induced by adding ssDNA oligonucleotides and varying certain parameters, providing a new dimension to the already versatile NACC system. We give valuable insights into the interplay between DNA and collagen in controlling gel properties. Through rheology and microscopy, we shed light on the variability between gels, paving the way for developing advanced biomaterials with precise control over their properties and functionalities. Our objective is to better understand the design capabilities achievable in this material system and provide proof of concept for the tunability of DNA-collagen hydrogels.

Results, Conclusions, and Discussions:
Our results indicate that all properties under investigation impact the gel's mechanical properties to a different extent. We confirm gel-like behavior of the NACCs and show that the addition of DNA aptamers to collagen results in a tunable hydrogel system, with variable material properties. This research indicates the ability to customize and tune the stiffness and elasticity depending on the fabrication method without additional stimuli. The impact of this technology lies in its ability to enable the development of more customizable material systems that can be fabricated with target properties for a broad variety of applications from cell-based applications to implantable material systems. NACCs are a versatile hydrogel platform that utilizes biocompatible building blocks, adjustable mechanical properties, and unique, highly specific biological functions.

Acknowledgments:
The authors would like to thank Anton Paar for use of their rheometer through the Anton Paar VIP research program . We also express our sincere gratitude to Bruker Nano Inc. for providing unique insights and support throughout the research process. This research was funded by the National Institutes of Health NIH R21 (#5R21GM146088-02) award to Josephine B. Allen