Microgel-Assisted Delivery of Adenosine to Accelerate Fracture Healing.

TitleMicrogel-Assisted Delivery of Adenosine to Accelerate Fracture Healing.
Publication TypeJournal Article
Year of Publication2022
AuthorsJ Hoque, Y Zeng, H Newman, G Gonzales, C Lee, and S Varghese
JournalAcs Biomaterials Science & Engineering
Volume8
Start Page4863
Issue11
Pagination4863 - 4872
Date Published11/2022
Abstract

Extracellular adenosine plays a key role in promoting bone tissue formation. Local delivery of adenosine could be an effective therapeutic strategy to harness the beneficial effect of extracellular adenosine on bone tissue formation following injury. Herein, we describe the development of an injectable in situ curing scaffold containing microgel-based adenosine delivery units. The two-component scaffold includes adenosine-loaded microgels and functionalized hyaluronic acid (HA) molecules. The microgels were generated upon copolymerization of 3-acrylamidophenylboronic acid (3-APBA)- and 2-aminoethylmethacrylamide (2-AEMA)-conjugated HA (HA-AEMA) in an emulsion suspension. The PBA functional groups were used to load the adenosine molecules. Mixing of the microgels with the HA polymers containing clickable groups, dibenzocyclooctyne (DBCO) and azide (HA-DBCO and HA-Azide), resulted in a 3D scaffold embedded with adenosine delivery units. Application of the in situ curing scaffolds containing adenosine-loaded microgels following tibial fracture injury showed improved bone tissue healing in a mouse model as demonstrated by the reduced callus size, higher bone volume, and increased tissue mineral density compared to those treated with the scaffold without adenosine. Overall, our results suggest that local delivery of adenosine could potentially be an effective strategy to promote bone tissue repair.

DOI10.1021/acsbiomaterials.2c00977
Short TitleAcs Biomaterials Science & Engineering