TY - JOUR
T1 - Injectable hydrogel for sustained delivery of progranulin derivative Atsttrin in treating diabetic fracture healing
AU - Moradi, Lida
AU - Witek, Lukasz
AU - Vivekanand Nayak, Vasudev
AU - Cabrera Pereira, Angel
AU - Kim, Ellen
AU - Good, Julia
AU - Liu, Chuan ju
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/10
Y1 - 2023/10
N2 - Hydrogels with long-term storage stability, controllable sustained-release properties, and biocompatibility have been garnering attention as carriers for drug/growth factor delivery in tissue engineering applications. Chitosan (CS)/Graphene Oxide (GO)/Hydroxyethyl cellulose (HEC)/β-glycerol phosphate (β-GP) hydrogel is capable of forming a 3D gel network at physiological temperature (37 °C), rendering it an excellent candidate for use as an injectable biomaterial. This work focused on an injectable thermo-responsive CS/GO/HEC/β-GP hydrogel, which was designed to deliver Atsttrin, an engineered derivative of a known chondrogenic and anti-inflammatory growth factor-like molecule progranulin. The combination of the CS/GO/HEC/β-GP hydrogel and Atsttrin provides a unique biochemical and biomechanical environment to enhance fracture healing. CS/GO/HEC/β-GP hydrogels with increased amounts of GO exhibited rapid sol-gel transition, higher viscosity, and sustained release of Atsttrin. In addition, these hydrogels exhibited a porous interconnected structure. The combination of Atsttrin and hydrogel successfully promoted chondrogenesis and osteogenesis of bone marrow mesenchymal stem cells (bmMSCs) in vitro. Furthermore, the work also presented in vivo evidence that injection of Atsttrin-loaded CS/GO/HEC/β-GP hydrogel stimulated diabetic fracture healing by simultaneously inhibiting inflammatory and stimulating cartilage regeneration and endochondral bone formation signaling pathways. Collectively, the developed injectable thermo-responsive CS/GO/HEC/βG-P hydrogel yielded to be minimally invasive, as well as capable of prolonged and sustained delivery of Atsttrin, for therapeutic application in impaired fracture healing, particularly diabetic fracture healing.
AB - Hydrogels with long-term storage stability, controllable sustained-release properties, and biocompatibility have been garnering attention as carriers for drug/growth factor delivery in tissue engineering applications. Chitosan (CS)/Graphene Oxide (GO)/Hydroxyethyl cellulose (HEC)/β-glycerol phosphate (β-GP) hydrogel is capable of forming a 3D gel network at physiological temperature (37 °C), rendering it an excellent candidate for use as an injectable biomaterial. This work focused on an injectable thermo-responsive CS/GO/HEC/β-GP hydrogel, which was designed to deliver Atsttrin, an engineered derivative of a known chondrogenic and anti-inflammatory growth factor-like molecule progranulin. The combination of the CS/GO/HEC/β-GP hydrogel and Atsttrin provides a unique biochemical and biomechanical environment to enhance fracture healing. CS/GO/HEC/β-GP hydrogels with increased amounts of GO exhibited rapid sol-gel transition, higher viscosity, and sustained release of Atsttrin. In addition, these hydrogels exhibited a porous interconnected structure. The combination of Atsttrin and hydrogel successfully promoted chondrogenesis and osteogenesis of bone marrow mesenchymal stem cells (bmMSCs) in vitro. Furthermore, the work also presented in vivo evidence that injection of Atsttrin-loaded CS/GO/HEC/β-GP hydrogel stimulated diabetic fracture healing by simultaneously inhibiting inflammatory and stimulating cartilage regeneration and endochondral bone formation signaling pathways. Collectively, the developed injectable thermo-responsive CS/GO/HEC/βG-P hydrogel yielded to be minimally invasive, as well as capable of prolonged and sustained delivery of Atsttrin, for therapeutic application in impaired fracture healing, particularly diabetic fracture healing.
KW - Atsttrin
KW - Diabetes
KW - Fracture healing
KW - Impaired fracture healing
KW - Injectable hydrogel
KW - Progranulin
UR - http://www.scopus.com/inward/record.url?scp=85169025890&partnerID=8YFLogxK
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U2 - 10.1016/j.biomaterials.2023.122289
DO - 10.1016/j.biomaterials.2023.122289
M3 - Article
C2 - 37639975
AN - SCOPUS:85169025890
SN - 0142-9612
VL - 301
JO - Biomaterials
JF - Biomaterials
M1 - 122289
ER -