TY - JOUR
T1 - Using dynamic biomaterials to study the temporal role of bioactive peptides during osteogenesis
AU - Fumasi, Fallon M.
AU - MacCulloch, Tara
AU - Bernal-Chanchavac, Julio
AU - Stephanopoulos, Nicholas
AU - Holloway, Julianne L.
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2024/2
Y1 - 2024/2
N2 - The extracellular matrix is a highly dynamic environment, and the precise temporal presentation of biochemical signals is critical for regulating cell behavior during development, healing, and disease progression. To mimic this behavior, we developed a modular DNA-based hydrogel platform to enable independent and reversible control over the immobilization of multiple biomolecules during in vitro cell culture. We combined reversible DNA handles with a norbornene-modified hyaluronic acid hydrogel to orthogonally add and remove multiple biomolecule-DNA conjugates at user-defined timepoints. We demonstrated that the persistent presentation of the cell adhesion peptide RGD was required to maintain cell spreading on hyaluronic acid hydrogels. Further, we discovered the delayed presentation of osteogenic growth peptide (OGP) increased alkaline phosphatase activity compared to other temporal variations. This finding is critically important when considering the design of OGP delivery approaches for bone repair. More broadly, this platform provides a unique approach to tease apart the temporal role of multiple biomolecules during development, regeneration, and disease progression.
AB - The extracellular matrix is a highly dynamic environment, and the precise temporal presentation of biochemical signals is critical for regulating cell behavior during development, healing, and disease progression. To mimic this behavior, we developed a modular DNA-based hydrogel platform to enable independent and reversible control over the immobilization of multiple biomolecules during in vitro cell culture. We combined reversible DNA handles with a norbornene-modified hyaluronic acid hydrogel to orthogonally add and remove multiple biomolecule-DNA conjugates at user-defined timepoints. We demonstrated that the persistent presentation of the cell adhesion peptide RGD was required to maintain cell spreading on hyaluronic acid hydrogels. Further, we discovered the delayed presentation of osteogenic growth peptide (OGP) increased alkaline phosphatase activity compared to other temporal variations. This finding is critically important when considering the design of OGP delivery approaches for bone repair. More broadly, this platform provides a unique approach to tease apart the temporal role of multiple biomolecules during development, regeneration, and disease progression.
KW - DNA
KW - Hyaluronic acid
KW - Hydrogels
KW - Osteogenesis
KW - Osteogenic growth peptide
KW - Reversible biomaterials
UR - http://www.scopus.com/inward/record.url?scp=85179880498&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85179880498&partnerID=8YFLogxK
U2 - 10.1016/j.bioadv.2023.213726
DO - 10.1016/j.bioadv.2023.213726
M3 - Article
C2 - 38096646
AN - SCOPUS:85179880498
SN - 2772-9508
VL - 157
JO - Biomaterials Advances
JF - Biomaterials Advances
M1 - 213726
ER -