Professor University of Florida, Florida, United States
Introduction: In the pursuit of integrating active targeting strategies in biomaterial scaffolds while also maintaining biomimicry, biocompatibility, and tunability, Nucleic Acid-Collagen Complexes (NACCs) show great promise. This study explores the potential of NACCs as a versatile therapeutic delivery system with wide-ranging applicability, focusing on the natural affinity of single-stranded DNA (ssDNA) and collagen type I. Upon mixing, these two biomacromolecules spontaneously self-assemble into a fibrous network that resembles the native extracellular matrix (ECM) fibrillary microarchitecture and demonstrate promising bioactivity, particularly with aptamer-specific ssDNA oligonucleotides. While existing work suggests NACC-induced cell signaling applications in bone tissue engineering and angiogenic-like endothelial cell phenotypes, the potential of NACCs to act as scaffolds for controlled therapeutic delivery remains unexplored.
Materials and
Methods: We utilized a well-characterized platelet-derived growth factor (PDGF)-binding aptamer. As controls, we used an oligonucleotide sequence of the same length not known to have any binding function towards PDGF. To assess the ability of NACCs for tailored growth factor release, we fabricated NACCs using different aptamer concentrations, as well as added complementary oligonucleotides to promote aptamer-collagen dissociation and cause the release of PDGF. Quantification of release kinetics of PDGF from the NACCs was performed using enzyme-linked immunosorbent assays (ELISAs).
Results, Conclusions, and Discussions: Our findings elucidate ssDNA's role in facilitating controlled release while in complex with collagen. The PDGF-sequestering aptamer was able to bind PDGF growth factor and release it at different rates depending on tailorable parameters such as the presence of complementary oligonucleotide sequences and aptamer concentration. The function-specific aptamer was found to retain PDGF, in contrast to the control which did not exhibit significant retainment capacity.
This work is a proof-of-concept for a tailorable growth factor release system, that could also be used in additional applications such as anticancer therapies or tissue engineering. PDGF sequestration and release were demonstrated in NACCs functionalized with a function-specific DNA aptamer, with the release rate being significantly different compared to random DNA sequences or collagen devoid of ssDNA. NACCs emerge as a versatile biomaterial platform, offering tunable composition and structure. The simplicity and adaptability of NACCs hint at their transformative potential in advanced biomaterial design, showcasing utility across various cell and tissue engineering domains as well as therapeutic drug delivery and release.
Acknowledgements (Optional): This research was funded by the National Institutes of Health NIH R21 (#5R21GM146088-02) award to J.B. Allen
