Streptavidin functionalized hyaluronic acid hydrogels for controlled and customizable drug delivery
5 affiliations
- 1Department of Bioengineering, University of Pennsylvania, 210 S. 33 Street, 240 Skirkanich Hall, Philadelphia, PA 19104, USA
- 2McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, 3450 Hamilton Walk, Stemmler Hall, Philadelphia, PA 19104, USA
- 3CReATE Motion Center and Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, 3900 Woodland Avenue, Philadelphia,PA 19104, USA
- 4BioFrontiers Institute and Department of Chemical and Biological Engineering, University of Colorado, 3415 Colorado Avenue, Boulder, CO 80303, USA
- 5Department of Physical Medicine and Rehabilitation, University of Pennsylvania, 1800 Lombard Street, Philadelphia, PA 19146, USA
Abstract
Hyaluronic acid (HA)-based hydrogels have emerged as promising materials for tissue repair given their ability to rapidly gel in situ to precisely fill tissue defects, their mechanical tunability and customizable degradation kinetics, and their capacity to deliver therapeutic agents to the site of injury. HA hydrogels can also be used to encapsulate therapeutics for local delivery; however, release through diffusion may be too rapid to achieve a therapeutic window for many applications. To overcome this limitation, we functionalized norbornene-modified HA (NorHA) hydrogels with streptavidin using thiol-ene click chemistry, enabling efficient tethering of biotin-modified agents (i.e., fluorophores, liposomes) to the hydrogel. We first confirmed that streptavidin functionalization increased the retention of encapsulated agents both in vitro and in vivo and did not impact hydrogel properties (including rapid gelation or mechanical tunability). Next, we incorporated matrix metalloproteinase (MMP) degradable crosslinks to further tune hydrogel degradation, permitting increased cellular invasion in vivo without disrupting retention and delivery of biotin-modified fluorophores. Lastly, streptavidin functionalized hydrogels were used to encapsulate and control the release of liposomes, with customizable release of model therapeutics within the liposome core and membrane. Overall, these findings support a promising material to control the release of therapeutics that could be useful in a variety of biomedical applications.
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BibTeX
@article{sharp2026streptavidin,
title = {{Streptavidin functionalized hyaluronic acid hydrogels for controlled and customizable drug delivery}},
author = {Emily E. Sharp and Lorielle Laforest and Yuqi Zhang and Karen L. Xu and Zhiliang Cheng and Jason A. Burdick and Sarah E. Gullbrand and Robert L. Mauck},
journal = {Acta biomaterialia},
year = {2026},
month = jul,
doi = {10.1016/j.actbio.2026.07.015},
url = {https://doi.org/10.1016/j.actbio.2026.07.015},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Streptavidin functionalized hyaluronic acid hydrogels for controlled and customizable drug delivery
AU - Emily E. Sharp
AU - Lorielle Laforest
AU - Yuqi Zhang
AU - Karen L. Xu
AU - Zhiliang Cheng
AU - Jason A. Burdick
AU - Sarah E. Gullbrand
AU - Robert L. Mauck
PY - 2026
DA - 2026/07/11
JO - Acta biomaterialia
DO - 10.1016/j.actbio.2026.07.015
UR - https://doi.org/10.1016/j.actbio.2026.07.015
AB - Hyaluronic acid (HA)-based hydrogels have emerged as promising materials for tissue repair given their ability to rapidly gel in situ to precisely fill tissue defects, their mechanical tunability and customizable degradation kinetics, and their capacity to deliver therapeutic agents to the site of injury. HA hydrogels can also be used to encapsulate therapeutics for local delivery; however, release through diffusion may be too rapid to achieve a therapeutic window for many applications. To overcome this limitation, we functionalized norbornene-modified HA (NorHA) hydrogels with streptavidin using thiol-ene click chemistry, enabling efficient tethering of biotin-modified agents (i.e., fluorophores, liposomes) to the hydrogel. We first confirmed that streptavidin functionalization increased the retention of encapsulated agents both in vitro and in vivo and did not impact hydrogel properties (including rapid gelation or mechanical tunability). Next, we incorporated matrix metalloproteinase (MMP) degradable crosslinks to further tune hydrogel degradation, permitting increased cellular invasion in vivo without disrupting retention and delivery of biotin-modified fluorophores. Lastly, streptavidin functionalized hydrogels were used to encapsulate and control the release of liposomes, with customizable release of model therapeutics within the liposome core and membrane. Overall, these findings support a promising material to control the release of therapeutics that could be useful in a variety of biomedical applications.
SN - 1742-7061
SN - 1878-7568
ER -